THE PCCA BLOG

Know Pain, Know Gain

Wed, 03 Sep 2025 13:26:00 GMT

I’m honored to be speaking at ThinkNext 2025, where I’ll deliver a lecture on the Neuroscience of Pain. This presentation will explore how modern pain science is revolutionizing our understanding of pain and unlocking powerful, non-pharmacologic strategies to improve patient care.

The Pain Crisis: Time for a Paradigm Shift

The pain epidemic and its devastating link to the opioid crisis is well-documented. As a health care community, we must do better. Our patients deserve it. Fortunately, the last two to three decades have ushered in a “pain revolution,” dramatically expanding our understanding of the human pain experience. Gone are the days when pain was simply equated with tissue damage. The outdated formula of “injury = pain” no longer holds. We now recognize pain as a complex, multifactorial experience involving:

Sensitization of peripheral and central nervous systems
Functional and structural changes in the brain
Psychosocial influences
Neuroplasticity and bioplasticity
Immune system alterations
And much more

Part I: The Latest in Pain Neuroscience

At ThinkNext, I'll introduce an overview of cutting-edge pain neuroscience and its implications for clinical practice. We’ll explore pain phenotyping, outline a precision medicine approach and examine the mechanisms behind:

Nociceptive-driven pain
Peripheral neuropathic pain
Central sensitization (nociplastic pain)

This research will challenge outdated models and highlight how evolving science can reshape our response to pain and the opioid epidemic.

Part II: Translating Science into Non-Pharmacologic Care

In light of the opioid crisis and in alignment with global guidelines, pharmacologic interventions must no longer be the default approach to chronic pain. At ThinkNext, I’ll also delve into how advances in neuroscience now support a range of evidence-based, non-pharmacologic treatments that activate endogenous pain-relief mechanisms and reduce reliance on medication.

You’ll learn about the three key domains that we must address to truly transform lives affected by persistent pain:

Cognitive: Therapeutic cognitive strategies can reduce fear-avoidance, catastrophizing, depression and anxiety. Changing pain behavior begins with changing beliefs.
Movement: Once fear is addressed, movement becomes one of the most potent tools for pain relief, whether through aerobic exercise, resistance training or recreational activity.
Nervous System Down-Regulation: Persistent pain often stems from a hypervigilant nervous system. Calming it, preferably through non-pharmacologic means, is essential. Techniques include relaxation, sleep hygiene, nutrition, breathing exercises and more.

The Power of Words

Pain is a normal, necessary human experience. Chronic pain is not. Pain that is understood is pain that need not be feared. Every health care provider communicates with patients and as Rudyard Kipling once said in a 1923 address to the Royal College of Surgeons: “Words are, of course, the most powerful drug used by mankind.”

This October, join me as we journey from tissues through C-fibers, into the dorsal horn, second-order neurons and the brain’s distributed neuromatrix. Let’s deepen our understanding of pain and use this knowledge to engage meaningfully with every patient we meet, transforming their experience of pain and suffering.

Building Stronger Veterinary Connections: Marketing Strategies for Compounding Pharmacies

Wed, 13 Aug 2025 15:06:00 GMT

by Mark Gonzalez, PharmD, PCCA Clinical Compounding Pharmacist

As compounding pharmacists, we’re used to juggling complex responsibilities — solving medication challenges with creativity, staying up to date with evolving science and technology, responding promptly to patients and prescribers, and carrying ourselves with professionalism in all situations. But there's one more responsibility that’s just as critical, yet often underutilized: marketing. Marketing is more than selling a product or service — it’s about building relationships. For compounding pharmacies looking to grow their veterinary services, effective marketing can make the difference between staying invisible or becoming indispensable.

Rethinking Marketing: Relationships Over Revenue

Some define marketing as advertising and sales. But for compounders, a more fitting definition might be this: “the pursuit, establishment and nurturing of relationships between a business and its customers.” Just like compounding itself, marketing is personal. The truth is, no matter how exceptional your service is, if veterinarians and pet owners don’t know you exist — or don’t understand what you offer — your efforts may go unnoticed. That’s why investing in relationship-driven marketing is essential to your success.

Veterinary Compounding: A Crowded and Competitive Space

The veterinary compounding niche is competitive, and many pharmacists find it challenging to break in. National players dominate with broad offerings and low prices, making it difficult for local compounders to stand out — unless they market themselves strategically. Thankfully, there are proven, real-world strategies you can adopt — not theoretical ideas, but battle-tested, cost-effective tactics that build long-term partnerships with veterinary clinics and pet owners. Let’s explore how innovation, education, responsiveness and professionalism — four values we already live by — can be harnessed for impactful marketing.

Innovative Marketing: Be Memorable

Great marketing, like great compounding, is all about creativity. Most veterinary offices are flooded with generic brochures and long lists of formulations. That’s why it pays to be different. One of the most successful veterinary marketing campaigns I’ve used involved something delightfully simple: a homemade brownie board. Here’s how it worked: I engraved my pharmacy’s contact information onto a 12x18 wooden cutting board, stacked it with homemade brownies and dropped it off at veterinary offices. Each board came with a standing invitation — call me for a brownie refill and get a quick update on the “Veterinary Concept of the Month.” It was a hit. The staff started calling me — not the other way around. It turned cold calls into warm conversations. And best of all, it cost very little. The takeaway? Good food and creative thinking can be a powerful gateway to meaningful relationships.

Educational Marketing: Empower Pet Owners

Your target audience isn’t just veterinarians — it’s also pet owners. They are, after all, the ones giving medications at home, and their experience can make or break treatment outcomes. Hosting an in-store or community seminar is a great way to connect. Use the opportunity to educate families on the basics of medicating pets: how species differ, what dosage forms are available and tips for handling picky patients. These events don’t have to be elaborate — just an hour of your time can deliver significant impact. An informed pet owner is more likely to return to your pharmacy and recommend your services. Education builds trust, and trust builds loyalty.

Responsive Marketing: Be the Local Lifeline

One area where local compounders have a natural advantage over national competitors is responsiveness. While large multistate veterinary compounders often offer attractive pricing, they may struggle with turnaround time and shipping costs. That’s where you step in. Market your pharmacy as a fast, responsive, locally rooted alternative. Emphasize your ability to provide same-day or next-day service, consult directly with the veterinarian and tailor compounds to the patients’ needs — without the wait. Even if you don’t get every order, you’ll become the go-to provider when time is critical or when a personal touch is needed.

Professional Marketing: Lead With Compassion

Marketing doesn’t always look like a pitch. Sometimes, it looks like a kind gesture. One of the most impactful forms of outreach I’ve seen is also one of the simplest: sending a handwritten sympathy card when a pet passes away. A custom memorial plaque with the pet’s name and photo can mean the world to a grieving family. These moments of compassion don’t go unnoticed. They show your pharmacy isn’t just a business — it’s part of the community. And that level of sincerity builds deeper emotional connections than any ad ever could.

Final Thoughts: Lead With Heart

Marketing doesn’t have to be complicated, expensive or pushy. When done with authenticity and purpose, it becomes a natural extension of the values that already define our profession. Whether you’re just starting to build your veterinary services or looking to deepen your existing relationships, think beyond flyers and discounts. Think about how you can show up — creatively, educationally, responsively and compassionately — for both veterinary professionals and pet owners. Because the best marketing isn’t about getting attention. It’s about earning trust.

What goes into a PCCA Formula?

Tue, 10 Jun 2025 14:24:00 GMT

If you've ever downloaded a formula from the PCCA database and thought, “Wow, that was easy,” you’re not wrong — but behind that single click is a mountain of work, innovation and science. In a recent episode of The Mortar & Pestle podcast, PCCA Senior Formulation Specialist & Project Manager Stacey Lemus, BS, gave us a behind-the-scenes look at the engine that drives PCCA’s formulation development.

For compounders, this isn’t just nitty gritty minutiae — it’s a reminder of the care, rigor and intelligence behind every formula you use.

The Formulation Team: Small but Mighty

PCCA’s Formulation Development team is a tight crew of eight, including four compounding pharmacists, two lab formulation specialists, a PhD scientist and the legendary Martha — an admin powerhouse who’s been with PCCA since the typewriter era. This team works across departments and alongside the Research & Development and Clinical Services teams to develop, review, test and refine more than 9,000 formulations in the database.

From Idea to Tested Formula

A formulation request can be driven by a whole host of needs — new APIs, novel dosage forms, drug shortages or general requests. Regardless of where it comes from, every request undergoes a thorough review process:

Clinical need: Is there a therapeutic gap this formula fills?
Feasibility: Will it compound well? Is it chemically compatible? Do we have the necessary excipients and equipment?
Regulatory compliance: Does it meet FDA’s 503A and USP requirements?
Stability and performance: Will it hold up for its full beyond-use date?

Some formulations are picture-perfect on the first try. Others go through 10, 15 or even 20 trials. The work doesn’t stop at “good enough” — it continues until the formula is not just viable but reproducible.

The Evolution of Bases — and What It Means for You

New bases like SuspendIt® and Anhydrous SuspendIt® have changed the game in oral suspensions. But they’ve also added complexity for the team. Creating a new base means evaluating hundreds of popular formulations to determine which should be updated, expanded or recreated using the new vehicle.

Important insight: older formulas aren’t necessarily retired — they’re often maintained to serve specific patient needs (e.g., sugar-free, soy-free or minimal excipient formulas).

The team now also develops formulations using commercially available drug products (CADPs), a nod to real-world pharmacy workflows, shortages and cost constraints.

Why Substitutions Can Be Challenging

One of the biggest member questions? “Can I sub out this base or excipient?”

Short answer: maybe — but tread carefully. Swapping a wetting agent, changing a flavor or using a different supplier's chemical could alter solubility, stability or even trigger unwanted chemical reactions — especially in anhydrous systems.

Many of PCCA’s formulas do more than provide instructions — they act as data-driven blueprints based on PCCA products. And that data isn’t cheap — FormulaPlus™ studies can cost up to $50,000 each to develop.

FormulaPlus: The Gold Standard

As of today, there are over 225 FormulaPlus formulations in the PCCA database. These extended beyond-use date formulas are tested using stability study protocols that utilize stability-indicating assays, along with USP 51 antimicrobial effectiveness and container closure testing, when applicable.

About 75 of them are bracketed, meaning they apply to a range of strengths, giving pharmacists more flexibility without compromising stability.

And this number is growing — PCCA adds approximately 20 new FormulaPlus studies each year.

Lessons from the Bench

Stacey’s personal journey — from compounding technician in a member pharmacy to developing formulation processes at PCCA — underscores one powerful message: Never stop learning.

In her early days, she didn’t understand why a cream got gritty over time or how an ointment mill worked beyond “reducing grittiness.” Now, she knows those issues stemmed from solubility limits, precipitation or particle size — and that the “why” matters just as much as the “what.”

For technicians and pharmacists alike, Stacey encourages ongoing education and a healthy respect for the science behind compounding. PCCA’s blog and training resources offer valuable insights into choosing the right wetting agents, gelling agents, preservatives and more.

Final Takeaway: It’s More Than Just a Formula

When you pull a formulation from the PCCA database, you’re benefiting from:

Months of lab work
Hours of research
Decades of experience
Cross-functional teamwork
Real-world applicability
Regulatory foresight
And sometimes 20+ failed attempts before that successful one

It’s not just a number on a page — it’s an investment in your success.

PCCA members with clinical services access can explore the full formula database anytime. Curious about membership? Find out how a PCCA membership can benefit your compounding practice.

Importance of Content Uniformity in Suspensions

Wed, 08 Jan 2025 19:14:53 GMT

by Maria Carvalho, PharmD, MRPharmS, PhD, PCCA Manager of PCCA Science

Suspensions are pharmaceutical dosage forms consisting of insoluble active ingredients dispersed in a base vehicle. An ideal suspension should be uniform in content so each dose contains an equivalent amount of one or more — most likely one — active pharmaceutical ingredients (APIs). We briefly review oral suspensions and why content uniformity is vital in compounded preparations, as well as showcase the most studied oral suspension, in the following article.

Liquid Suspensions and Content Uniformity

The type of suspension used to compound preparations depends on the route of administration: oral, topical or injectable. Oral liquid suspensions are advantageous in their ability to provide an easy-to-swallow medication for pediatric, geriatric and patients challenged by other dosage forms such as tablets and capsules. However, due to the heterogeneous nature of liquid suspensions, insoluble APIs tend to settle at the bottom of containers when standing. For this reason, if patients or caregivers forget to agitate — or shake — the preparation or do not agitate it adequately before administration, the content uniformity and dosing accuracy of the APIs may be compromised.

Content uniformity, defined as the consistency in the amount of APIs among dosage units, is determined by performing a series of tests using APIs and the suspension vehicle. An ideal suspension should retain content uniformity so that each dose contains an equivalent amount of APIs. As such, content uniformity is highly dependent on the characteristics of the suspension. If a suspending vehicle is too viscous — or has a thick and sticky consistency — APIs are not easily dispersed. In contrast, if the suspending vehicle is too thin, the APIs will settle at the bottom of the container.¹

The Superior Liquid Vehicle

PCCA SuspendIt® (PCCA #30-4825) is our “all-in-one” aqueous (water activity [aw] > 0.6) oral suspension vehicle. It contains a synergistic polymer complex that offers a unique thixotropic flow — which means it thins when shaken and thickens upon standing — that allows rapid redispersion of APIs and minimizes sedimentation. Made with an all-natural sweetener derived from monk fruit, SuspendIt is an ideal choice for patients requiring formulations without sugar, casein or gluten.

As an aqueous oral suspension, SuspendIt uses potassium sorbate and sodium benzoate as preservatives. The November 2023 revisions to the United States Pharmacopeia (USP) 795 offer beyond-use dates (BUDs) of up to 35 days for an aqueous, preserved preparation.

Although SuspendIt may be used in veterinary preparations, it’s important to recognize that in felines, sodium benzoate can be a potential toxin when chronically administered and use should be limited to two weeks.

Suspendit is featured in a number of USP compounded preparation monographs and is currently one of the most studied oral vehicles in the compounding industry. SuspendIt studies, including scientific journal abstracts, scientific posters and a technical report summarizing the content uniformity of eight SuspendIt formulations, are available in SuspendIt Scientific Publications.

Competitor Suspension vs. SuspendIt

Within one minute, this timelapse video shows the content uniformity between SuspendIt and a competitor’s suspension base over the course of five days.

PCCA members with clinical services access may view and/or download PCCA SuspendIt formulations — including formulas with FormulaPlus™ BUD Studies — after logging on to our Members-Only Website. Clinical services access also allows members to contact our Clinical Services team for additional information on compounding SuspendIt preparations and other compounding concerns.

PCCA is recognized as the leader of quality products, education and advocacy in the compounding industry. Find out how a PCCA membership can benefit your compounding practice.

References

PCCA Science Technical Report. Evaluation of the Content Uniformity of 8 SuspendIt® Formulations. 2015. Accessed January 2025 at https://beta.pccarx.com/pdf_files/98962_TR_SuspendIt_ContentUnif.pdf

These statements are provided for educational purposes only. They have not been evaluated by the Food and Drug Administration, and are not to be interpreted as a promise, guarantee or claim of therapeutic efficacy or safety. The information contained herein is not intended to replace or substitute for conventional medical care or encourage its abandonment.

Penetrating the Nail Fungus Market with EctoSeal P2G™

Wed, 04 Dec 2024 18:13:00 GMT

by Sam Hamburger, PharmD Candidate, PCCA Clinical Services Intern, and Mark Gonzalez, PharmD, PCCA Clinical Compounding Pharmacist

One of the most valuable benefits of PCCA membership is access to our knowledgeable Research & Development department and their compounding base innovations. Their creativity has led the industry and provided resources that benefit thousands of patients every day. This post focuses on a powerful base launched in 2023, EctoSeal P2G, and its application in one of the most common dermatological conditions — nail fungus (onychomycosis).

Beyond Basic: EctoSeal P2G

EctoSeal P2G (powder to gel) was developed by the PCCA R&D department and released in 2023. It is one of the most innovative and clinically versatile bases in the compounding industry, with seemingly limitless potential. The base itself is available as a powder that can be compounded with a wide variety of active pharmaceutical ingredients (APIs) and dispensed in one of three unique dosage forms: a powder, a powder for reconstitution or a hydrogel. Each dosage form has unique and versatile therapeutic possibilities. Regardless, the end goal of this base is to form a protective film over the affected area, delivering the API while simultaneously shielding the area and enhancing the skin’s local microbiome. It is also easily removed by simply rinsing with water, which causes the film to revert to a liquid gel that will simply wash off.

As a compounder, you are by definition a creative individual. Imagine the possibilities of compounding a preparation that creates a microbiome-enhancing protective film — one that easily washes off with water, easing the discomfort experienced by wound patients during dressing changes or Polyox bandage removal. Coupled with the imagination and ingenuity of PCCA members, we have seen incredible advances beyond wound care in conditions such as acne, diaper rash, excoriated eczema, veterinary infections, vaginal/rectal lesions and most recently, nail fungus (onychomycosis).

Onychomycosis

For decades, compounders have formulated prescriptions for use on patients with onychomycosis. The condition occurs in 10 percent of the general population, 20 percent of persons older than 60 years and 50 percent of those older than 70 years. Although caused by a variety of organisms, most cases are created by dermatophytes, a pathogenic fungus that causes ringworms and other diseases.¹ Topical preparations have often been preferred over oral therapies due to a lower side effect profile.

The vehicle of choice to deliver compounded antifungal agents has traditionally been dimethyl sulfoxide (DMSO) because of its ability to solubilize many APIs and penetrate various tissues. For antifungal preparations to be effective, transungal (through the nail) penetration is crucial to eliminate an infection that resides in the nail and nail bed.

EctoSeal P2G Study

Recognizing EctoSeal P2G’s excellent film-forming property, the PCCA Science team tested and measured the vehicle’s drug delivery potential in the nail using two PCCA formulas containing EctoSeal P2G, then compared those formulations with a standard formula involving APIs and DMSO alone. Five volunteers who met study eligibility criteria provided nail clippings, which were coated with one of the following compounded formulations:

Fluconazole 2%/Ibuprofen 2% Topical Nail Hydrogel (EctoSeal P2G)
Fluconazole 2% Topical Nail Hydrogel (EctoSeal P2G)
Fluconazole 2%/Ibuprofen 2%/Dimethyl Sulfoxide (DMSO) Nail Solution

After the compounds were applied to the nail clippings and allowed to dry for 48 hours, the clippings were washed to remove any drug residue. Ultra-Performance Liquid Chromatography (UPLC), a liquid chromatography technique that uses high pressure and new column technologies to separate compounds in complex mixtures, was used to measure the amount of drug in the pulverized nail clippings. When compared to the DMSO solution delivery, both EctoSeal P2G formulations resulted in much higher concentrations of drug (approximately 50 percent more) within the nail plate. This proves that an EctoSeal P2G/DMSO mixture is more effective at delivering drugs into the nail than DMSO alone.²

Compounders now have reliable data to present to dermatologists, podiatrists and general practitioners who have not found success with commercially available options for onychomycosis. Marketing this study may also broaden the practitioner’s imagination regarding the use of the film-forming possibilities of EctoSeal P2G. As compounders, we can take advantage of this data and innovative base vehicle to promote the endless opportunities that compounding can provide to solve medication problems and potentially improve patient outcomes.

Build and market your practice by promoting EctoSeal P2G:

As part of your next marketing campaign, take in or mail a sample of non-medicated EctoSeal P2G to your practitioners so they can experience its film-forming properties for themselves.
Provide copies of this study and other EctoSeal P2G studies to your practitioners and patients.
Compound with confidence knowing PCCA bases are backed by science and research.

PCCA members may learn more about EctoSeal P2G by watching a free webinar. PCCA members with clinical service access may contact our Clinical Services team for additional information on EctoSeal P2G and other compounding concerns.

PCCA is recognized as the leader of quality products, education and advocacy in the compounding industry. Find out how a PCCA membership can benefit your compounding practice.

References

Westerberg DP, Voyack MJ. Onychomycosis: Current trends in diagnosis and treatment. Am Fam Physician. 2013;88(11):762-770. Accessed November 2024 at https://pubmed.ncbi.nlm.nih.gov/24364524/
PCCA Research & Development. EctoSeal P2G (#30-5217) Science Manual. 2024; 8-9.

What’s in Store at the LDN Virtual Conference

Fri, 15 Nov 2024 03:53:03 GMT

Individuals who suffer from symptoms of gastrointestinal, autoimmune, dermatological and pain conditions make up 80% of the patient population. But here’s the good news: multiple studies indicate that low-dose naltrexone (LDN) may potentially help many of these conditions. Take a sneak peek at topics our Clinical Services team will discuss during the Low-Dose Naltrexone One-Day Virtual Conference on Thursday, November 21, 2024.

The Immune System — Autoimmune Conditions and the Benefits of LDN

by Catherine Henderson, PharmD, PCCA Clinical Compounding Pharmacist

LDN has long been touted for its effects in autoimmune disorders. Understanding the mechanisms of LDN action involves diving deeper into immune system function and the irregularities that occur in autoimmune disorders. We’ll explore the data related to LDN’s various mechanisms for improving disease symptomatology and quality of life, as well as review real world published studies and cases of LDN use in various autoimmune disorders.

Dermatological Inflammatory Diseases and LDN

by Nat Jones, RPh, FAPC, PCCA Clinical Compounding Pharmacist

LDN is growing in popularity in the dermatology world. It has proven to be beneficial for pruritus and inflammation due to its ability to attenuate toll-like receptors found in the skin. We’ll discuss two cases: one of a tattoo allergic reaction and one of hidradenitis suppurativa (HS). Tattoo reactions to the coloring agents can be intense and difficult to treat. HS is a chronic inflammatory, potentially scarring, skin disease primarily affecting apocrine gland-rich areas of the body (axillary, groin, perianal, perineal regions and abdominal folds), often mediating pain and considerable morbidity, both physical and psychological.

The Use of LDN in Veterinary Patients

by Katy Hecker, PharmD, PCCA Clinical Compounding Pharmacist

As pet owners, we lovingly share many things with our pets including treats, affection and half of the bed. Research suggests we also share similarities in physiological function, disease state manifestation and treatment modalities utilized. Join in the discussion and learn more about the science behind LDN for veterinary clinical indications including behavioral disorders, atopic dermatitis, osteoarthritis, cancer, inflammatory bowel disease (IBD) and more!

Perimenopause and Menopause Are Inflammatory Conditions: The Use of LDN for Hormones and Weight Loss

by Sara Hover, RPh, FAARM, PCCA Director of Clinical Services

Understanding the inflammatory processes that characterize perimenopause and menopause will shed light on how the hormonal changes contribute to weight gain and obesity. Central to this discussion is the shift in estrogen profiles — from estradiol, which possesses anti-inflammatory properties, to estrone, a pro-inflammatory estrogen that becomes predominant during menopause. This hormonal transition fosters an inflammatory state that can disrupt metabolism and promote adiposity. Additionally, the presentation will explore various options aimed at reducing inflammation and managing weight effectively. Key strategies include optimizing sleep quality, utilizing probiotics to support gut health and implementing LDN as an innovative therapeutic approach. Attendees will gain a comprehensive understanding of the biological mechanisms linking menopause to inflammation and weight gain, along with practical interventions to enhance health and well-being during this pivotal life stage.

Using LDN for Chronic Pain Conditions

by Tricia Heitman, PharmD, PCCA Clinical Compounding Pharmacist

LDN is gaining attention for its anti-inflammatory properties and its ability to manage pain and opioid addiction. By acting on the opioid receptors at lower doses, LDN enhances endorphin production, which can help reduce inflammation and alleviate pain associated with various conditions such as arthritis, fibromyalgia and autoimmune disorders. Many patients report significant relief from chronic pain and inflammation while taking LDN. We will discuss the appropriate doses and review the literature associated with LDN and pain.

LDN for Gut Inflammatory Disorders

by Ranel A. Larsen, PharmD, PCCA Clinical Compounding Pharmacist

LDN is emerging as a promising therapeutic option for enhancing gut health, particularly in the context of IBD and irritable bowel syndrome (IBS). LDN helps to regulate immune responses, improve epithelial barrier function and reduce inflammation within the gut, all of which are critical for maintaining intestinal homeostasis. In IBD, LDN may lower disease activity and enhance quality of life, while in IBS, it can alleviate symptoms such as pain and bloating. Overall, LDN's role in improving gut health underscores its therapeutic potential to support management of complex gastrointestinal disorders.

How to Market LDN Studies

by Mark Gonzalez, PharmD, PCCA Clinical Compounding Pharmacist

Today’s compounding pharmacist wanting to effectively market LDN to practitioners and patients has access to tools that were not as available 20 years ago when LDN started to become popular. Clinical studies, therapeutic reviews and case series are now readily available to substantiate what were once only theories on the effectiveness of naltrexone in autoimmune disorders. These studies span a wide array of specialties and medical conditions. Research groups such as the LDN Research Trust, publications such as the series of three LDN books and many of the clinical presentations given on the subject of LDN all reference these studies. The pharmacist and marketer must leverage the power of this data as part of their communication to both the practitioner and the patient they are marketing to. With the additional aid of social media, positive patient stories can accompany the data from these clinical studies to make for attractive and effective marketing.

Register for the Low-Dose Naltrexone One-Day Virtual Conference today and get more details — plus more information — on the potentials of LDN. We look forward to additional discussions and answering your questions!

Backed by Science: Anhydrous VersaBase® HRT

Tue, 12 Nov 2024 14:48:13 GMT

At PCCA Science, we continuously build and grow scientific support for compounding and the technologies our members use in their practices. We test our bases using various methods before, during and after the release of a new product. We regularly submit results of these studies for publication in peer-reviewed journals and make them available to our members, who in turn can share them with prescribers, physicians and patients.

In Vitro Evaluation of the Percutaneous Absorption of Progesterone in Anhydrous Permeation-Enhancing Base Using the Franz Skin Finite Dose Model and Mass Spectrometry

What does the study say?

This study, published in the Archives of Dermatological Research, compares how well progesterone penetrates the skin in two topical formulations: one using Anhydrous VersaBase HRT and the second using a non-ionic cream. Results of the study showed that Anhydrous VersaBase HRT had a 3.2-fold increase in skin penetration over the non-ionic cream base, indicating it may be a good base to use in topical progesterone formulations.

Figure 1: The Anhydrous VersaBase HRT formulation offered a 3.2-fold increase in optical density (p = 0.029) for progesterone penetrating layers of skin compared to the non-ionic cream formulation.

What do the results of the study mean to prescribers and physicians?

Progesterone in a topical preparation using Anhydrous VersaBase HRT shows exceptional delivery of the hormone through the skin compared to the standard non-ionic cream base. It also indicates that the stability and potency of progesterone in the Anhydrous VersaBase HRT formulation was consistent for more than 180 days. Consistent hormone delivery is commonly recognized as achieving optimal prescriptive therapeutic outcomes for patients.

What do the results mean to patients?

The 180 beyond-use date (BUD) means patients will make fewer trips to the pharmacy for refills. Consistent hormone delivery may potentially help patients achieve a better therapeutic outcome.

What does anhydrous mean and why is that important?

Literally, anhydrous indicates a substance that contains no water. For compounded preparations, it means the water activity (Aw) — or the amount of available water in a substance — is less than 0.6 (<0.6). This is important because compounded preparations with Aw <0.6 do not support the growth of bacteria, yeast or molds.

Get a summary of study methods, images, graphs and more here.

*USP 795 establishes BUD limits by type of preparation in the absence of a USP−NF Compounded Preparation Monograph or CNSP-specific stability information.

Progesterone: Size Matters

PCCA offers USP-grade Special Micronized Progesterone with an unparalleled particle size to promote better bioavailability:

100% <9 microns
99% <5 microns
90% <2 microns

Additional Benefits

Consistently sourced from FDA-registered and GMP-compliant facilities
Tested in PCCA formulations in a range of concentrations
Above and beyond USP standards

Low-Dose Naltrexone in the Oncology Setting

Wed, 06 Nov 2024 19:19:31 GMT

by Sebastian Denison, RPh, PCCA Clinical Compounding Pharmacist

Since 2014, there’s been an explosion of information about the potential applications of low-dose naltrexone (LDN), including use as an adjunct therapeutic in some types of cancer. The exploration of LDN in cancer treatment underscores the importance of understanding the complex interplay between immune signaling and cancer biology, which we discuss in the following article.

Understanding TLR Signaling and Inflammation

Toll-like receptors (TLRs) play a crucial role in detecting and responding to pathogens and initiating inflammation. TLR signaling culminates in the activation of key transcription factors such as nuclear factor kappa B (NF-κB) and activating protein-1 (AP-1).

These transcription factors regulate a multitude of genes, including those encoding important proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukins (IL-1, IL-6, IL-8, IL-12). Some TLRs also activate production of type 1 (alpha and beta) interferons by inducing the interferon regulatory factors (IRFs) IRF3, IRF5 and IRF7.¹

NF-κB has been implicated in the pathogenesis of a number of inflammatory diseases, such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis, atherosclerosis, systemic lupus erythematosus, type I diabetes, chronic obstructive pulmonary disease and asthma. It also links chronic inflammation to cancer.²

Ongoing inflammation can also contribute to a condition known as "inflammaging," characterized by elevated inflammatory markers in older adults, increasing their susceptibility to chronic diseases and frailty.³

LDN: A New Perspective in Oncology

Traditionally, naltrexone (NTX) was used in treating opioid and alcohol dependence. Emerging research indicates that LDN may have a significant impact on cancer progression. This is primarily mediated through its effects on the opioid growth factor receptor (OGFr) axis, which has been associated with cancer cell survival, proliferation and invasion.⁴

Mechanisms of Action

Antagonism of Receptors: LDN’s antagonistic effects extend to TLRs 7-9, which can lead to the suppression of IL-6, a cytokine often elevated in cancer. By inhibiting these receptors, LDN may help to modulate the inflammatory environment that tumors exploit for growth.
Modulation of Immune Function: LDN appears to enhance the immune response in patients, potentially leading to improved cancer control. By promoting the activity of immune cells, LDN may assist the body in recognizing and attacking cancer cells more effectively.
Inhibition of Signaling Pathways: LDN is shown to prime pro-apoptotic pathways, encouraging cancer cells to undergo programmed cell death. This mechanism is particularly advantageous in combination with other therapies such as chemotherapy and immunotherapy.⁵

Low vs. Standard Dose

The effectiveness of NTX is highly dependent on individual dosage. Standard doses (25-50 mg) exhibit a classic antagonistic effect on opioid receptors, while LDN (1-5 mg) creates a transient blockade. This low-dose administration results in a compensatory increase in the synthesis of endogenous opioid peptides, fostering a feedback mechanism that enhances the anti-cancer effects. Research led by McLaughlin emphasizes the importance of both dosage and duration of exposure to opioid receptor antagonists. LDN’s temporary blockade of the OGFr ultimately leads to an increase in the expression of various opioid receptors, which can inhibit DNA replication and limit cancer cell proliferation. Conversely, higher doses of NTX could promote cellular division, counteracting the intended therapeutic effects.⁶

Promising Preclinical Evidence

Numerous preclinical studies support the idea that LDN can positively impact cancer outcomes. These studies indicate that LDN may inhibit the OGFr-OGF signaling axis, leading to decreased cancer cell proliferation. The lack of direct cytotoxic effects, combined with its immunomodulatory properties, positions LDN as an appealing option for cancer patients, particularly when used in conjunction with conventional therapies.

As anecdotal reports and preliminary studies point towards its efficacy, there is a growing momentum for clinical trials assessing LDN in oncology. The promise of LDN lies in its unique mechanism of action, which harnesses the body’s own systems to combat cancer while potentially reducing the side effects associated with traditional chemotherapy.

PCCA Members: Are you curious to know more? Log on to the Members Only website and check out our free webinar, Low-Dose Naltrexone: What’s New?

References

McDonald D. Toll-like receptors: Roles in disease and therapy. UpToDate (2022; literature review current through May 2024). Accessed 2024 at https://medilib.ir/uptodate/show/3985
Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017;2:17023-. Accessed 2024 at https://pubmed.ncbi.nlm.nih.gov/29158945/
Ferrucci L, Fabbri E. Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nat Rev Cardiol. 2018;15(9):505-522. Accessed 2024 at https://pubmed.ncbi.nlm.nih.gov/30065258/
Belltall A, Mazzinari G, Diaz-Cambronero O, Eroles P, Argente Navarro MP. Antagonists of the Mu-Opioid Receptor in the Cancer Patient: Fact or Fiction?. Curr Oncol Rep. 2022;24(10):1337-1349. Accessed 2024 at https://pubmed.ncbi.nlm.nih.gov/35648340/
Liu WM, Dalgleish AG. Naltrexone at low doses (LDN) and its relevance to cancer therapy. Expert Review of Anticancer Therapy, 2022;(3), 269–274. Accessed 2024 at https://www.tandfonline.com/doi/citedby/10.1080/14737140.2022.2037426?scroll=top&needAccess=true
Ciwun M, Tankiewicz-Kwedlo A, Pawlak D. Low-Dose Naltrexone as an Adjuvant in Combined Anticancer Therapy. Cancers. 2024; 16(6):1240. Accessed 2024 at https://www.mdpi.com/2072-6694/16/6/1240

The Best Jam Compounding Fest in the Land — Until Next Year!

Wed, 30 Oct 2024 15:00:00 GMT

ThinkNext: International Seminar 2024 (ThinkNext: ISTX24), held October 17 - 19 in Houston, Texas, was a huge success with well over 500 rockstar compounders from around the world. We’re sharing seminar highlights and memorable takeaways that make PCCA members return year after year.

The following summaries, however, do not give justice to the many workshops and presentations offered at ThinkNext: ISTX24. Nor do they capture the energy, networking, educational pearls, laughter and good times shared. You’ve got to be there to fully appreciate and experience the best jam compounding fest in the land.

Clinical Presentations

Compounding Ideas for Dermatology and Wound Care
PCCA Clinical Pharmacist Nat Jones, RPh, FAPC, discussed compounding options for hair growth, ideas for topical anti-aging face formulations and understanding wounds and evaluation options for step-by-step wound care.
Hospice and Palliative Care in Veterinary Medicine
PCCA Vice President of Creative Development Chris Simmons, RPh, and PCCA Clinical Compounding Pharmacist Mark Gonzalez, PharmD, defined hospice and palliative care, described the disease states commonly seen in the veterinary hospice/palliative care setting, shared compounded options and discussed the value compounding brings to this area of veterinary medicine.

Innovation

Behind the Science: PCCA Innovation
PCCA Chief Scientific Officer Gus Bassani, PharmD, and PCCA Director of Research & Development Daniel Banov, RPh, MS, shared new data from scientific studies conducted on EctoSeal P2G ™ and SubMagna™ SL HMW that members can share with prescribers.
Leadership and How to Fail Like a Boss
Keynote speaker Dave Aspery, “the father of biohacking,” pointed out how the five F's: "fear, food, fertility, friends and forgiveness," drive a person's energy, also noting how our life expectancy and longevity are influenced by our physical and mental health.

Marketing

New Trends in Social Media
Magnolia Pharmacy owner and president Steve Hoffart, PharmD, shared tips on how to use social media to market your pharmacy in your community and to federal legislators.
A Practical Approach to AI and How I Use It
Las Colinas Compounding & Wellness Pharmacy’s Stacy Hightower, CPhT, FAPC, discussed game-changing AI and how she develops marketing campaigns, gains consumer insights and increases pharmacy revenue using this powerful tool.

Revenue Generation

Building Supplement Sales
PCCA Director of Member Engagement Erin Michael, MBA, MS, CPhT, FAPC, and PCCA Director of Business Solutions Laura Pfaffenberger, PharmD, discussed market trends for dietary supplements and how to tap into this lucrative niche.
What Is Your Job?
Williamsburg Drug Company owner and pharmacist T.W. Taylor, RPh, shared how consultation services provided by his pharmacy helped his patients restore their health and increase his pharmacy’s revenue.
Business Accelerator: Move Your Pharmacy Forward — Faster
PCCA Director of Business Solutions Laura Pfaffenberger, PharmD, took the stage and announced Business Accelerator, which offers workable solutions that address staffing, operations, strategy and growth specific to compounding pharmacies.

Regulatory Concerns

Implications of Your Marketing from a Regulatory Perspective
PCCA Clinical Services Director Matt Martin, PharmD, BCSCP, and PCCA Director of Member Engagement Erin Michael, MBA, MS, CPhT, FAPC, discussed the regulatory considerations that apply when promoting your practice, best practices for promoting your services without making claims and the standards images should meet before being used in promotional content.
PCCA Public Affairs
PCCA Vice President of Public Affairs, Education and Human Relations Lizzie Harbin opened the Regulatory, Public Affairs and Industry Partner Panel by discussing the importance of advocating for our industry. Lizzie then invited CEO of the Alliance for Pharmacy Compounding Scott Brunner, CAE, and CEO of the National Community Pharmacists Association Doug Hoey, RPh, MBA, to discuss imminent threats to pharmacies: compounding hormones, pharmacy benefit managers (PBMs) and direct and indirect remuneration (DIR) fees, as well as the role of telehealth in pharmacies.

Award-Winning Members

Joseph P. Navarra, RPh, FACA, FAPC, owner of Town Total Compounding Center in Woodbury, New York, and board chair of the Alliance for Pharmacy Compounding, was named PCCA’s 2024 M. George Webber, PhD, Compounding Pharmacist of the Year.
Stacy Hightower, CPhT, FAPC, of Las Colinas Pharmacy Compounding & Wellness in Irving, Texas, owned by Jim and Jan Hrncir, was honored as PCCA’s inaugural Compounding Technician of the Year.
Jerry Beamer, RPh, co-owner of Andrews Apothecary in Winston-Salem, North Carolina, was honored as the recipient of the 2024 L. David Sparks Advocacy Award.
Isha Gupta, PharmD, MBA, owner of HatchRx Compounding Pharmacy in Long Island, New York, was honored as the recipient of the 2024 George Roentsch, RPh, New Innovator Award.

We thoroughly enjoyed rocking out with our PCCA members, sponsors and friends and look forward to seeing more new and familiar faces next year at ThinkNext: International Seminar 2025 — the best jam compounding fest in the land.

Managing Menopausal Weight Gain: The role estrogen plays with GLP-1 agonists

Wed, 11 Sep 2024 13:27:35 GMT

by Katy Hecker, PharmD, PCCA Clinical Services

In a woman’s life, the absence of menstruation for 12 months marks the official beginning of menopause. Waning ovarian function coupled with declining circulating hormone levels spark natural menopause, but menopause may also occur as result of surgical procedures such as following a hysterectomy and/or oophorectomy. Commonly reported symptoms of menopause include hot flashes, night sweats, vaginal dryness, sleep disturbances, mood swings and weight gain,¹ with an estimated 70% of menopausal women experiencing weight gain.²

Menopause and Body Composition

Menopause triggers body composition changes such as increased abdominal adipose tissue and decreased lean muscle mass. This change in body composition intensifies the risk of diabetes, cardiovascular disease, dyslipidemia (abnormal levels of lipids in the blood) and metabolic dysfunction-associated steatotic (fatty) liver disease. Heart disease is the leading cause of death in women; therefore, it is critical to address menopausal weight gain and the cardiometabolic changes that occur. Hormone replacement therapy, lifestyle modification and in some instances medication therapy may be beneficial to help combat menopausal weight gain.^2,3

GLP-1 and Weight Loss

GLP-1 is a hormone naturally produced in the central nervous system, intestine and pancreas. It is released in response to the consumption of fats and carbohydrates.^2,4GLP-1 increases insulin secretion, decreases glucagon release, slows gastric emptying and reduces food intake. Research also suggests it may reduce food reward behavior. The appetite suppressing effect of GLP-1 is due to its action in the hypothalamus and brainstem. Interestingly, this is the same region of the brain responsible for the food intake reduction effects of estrogen. Glucagon-like peptide-1 (GLP-1) receptor agonist and dual agonist therapies are FDA-approved for the treatment of obesity, weight management, type 2 diabetes mellitus and cardiovascular mortality reduction.⁴

Semaglutide and Hormone Replacement Therapy

Combining hormone replacement therapy with semaglutide, a GLP-1 receptor agonist, may lead to better outcomes for total body weight loss and subsequent improvements in cardiometabolic health. A recent retrospective review compared weight loss response and cardiometabolic changes in post-menopausal women using semaglutide in combination with and without hormone therapy. At three, six, nine and 12 months following semaglutide initiation, women using hormone therapy experienced approximately 30% greater total body weight loss than the non-hormone therapy users. Both groups showed improvements in cardiometabolic health marked by lower fasting blood glucose, blood pressure, LDL, total cholesterol and triglycerides.²

Reward Eating, GLP-1 and Estrogen

Reward eating is comprised of two categories, “wanting” and “liking.”⁵ Liking is associated with the palatability of the food and wanting is food craving triggered by a cue or stimuli which then leads to motivation to obtain a specific type of food.⁴ Research suggests women may exert a greater response to a centrally administered long acting GLP-1 agonist on food reward due to the activation of central estrogen receptor alpha. This reduction was noted with the “wanting” subtype of reward eating in women greater so than men. A reduction in the “liking” subtype of reward eating was displayed in both men and women. Administration of an estrogen receptor antagonist was sufficient to blunt the effects of the central GLP-1 agonist on food reward behavior in both men and women. This evidence suggests the activation of central estrogen receptor alpha may be critical for central GLP-1 agonist’s effect on reward eating.^4,5

Compounded Medications

There are many treatment strategies that may help menopausal women with the natural challenges and health risks associated with this phase of life. Combining therapies has yielded compelling results, and compounded medications can be personalized to meet the needs of each patient, offering a unique solution for various medication related concerns. For example, SubMagnaTM SL HMW can be used to deliver semaglutide in a sublingual dosage form. This may improve adherence in patients who have trouble swallowing or who are fearful of needles.

Members with clinical services access may contact our Clinical Services Team for help with PCCA formulas and other compounding questions.

References

World Health Organization. Menopause [Internet]. Oct 2022. Accessed August 2024 at https://www.who.int/news-room/fact-sheets/detail/menopause
Hurtado MD, Tama E, Fansa S, et al. Weight loss response to semaglutide in postmenopausal women with and without hormone therapy use. Menopause. 2024;31(4):266-274. doi:10.1097/GME.0000000000002310
Centers for Disease Control. About Women and Heart Disease [Internet]. May 15, 2024. Accessed August 2024 at https://www.cdc.gov/heart-disease/about/women-and-heart-disease.html#:~:text=Heart%20disease%20is%20the%20leading,affect%20women%20at%20any%20age
Elsevier Clinical Pharmacology. Glucagon-like Peptide-1 (GLP-1) Receptor Agonists and Dual Agonists [Internet]. Apr 9, 2024. Accessed August 2024 at https://elsevier.health/en-US/preview/glucagon-like-peptide-1-glp-1-receptor-agonists
Richard JE, Anderberg RH, Lopez-Ferreras L, et al. Sex and estrogens alter the action of glucagon-like peptide-1 on reward. Biol Sex Differ. 2016;7:6. doi:10.1186/s13293-016-0059-9

SubMagna™ SL HMW: Delivery of APIs — Sublingually

Wed, 27 Mar 2024 17:48:08 GMT

by Christine Vu, BS, PCCA Senior Scientist/R&D Product Analyst

The PCCA Research & Development (R&D) team constantly explores innovative ways to help meet the unique needs of patients. Using a multi-disciplinary approach, we developed SubMagna SL HMW, a self-emulsifying, sublingual delivery system, to accommodate a wide range of drugs with varying molecular weights — including those with a high-molecular weight. This innovative base is another way PCCA helps to fill the unmet needs of patients, prescribers and compounding pharmacies.

Oftentimes, commercially available medications are designed as a one-size-fits-most solution; however, not all patients can tolerate commercially manufactured drugs. These patients need personalized options made available from compounding pharmacies.

Addressing the gap between available drugs and how they are delivered to patients is yet another way compounding helps solve medication challenges. Many pharmaceutical researchers are now focusing on developing high-molecular weight (HMW) therapeutics. Yet delivery methods for HMW drugs may pose additional challenges for patients and their healthcare providers. SubMagna SL HMW can help compounders provide a solution to these and other challenges.

Drug Delivery Systems

New and emerging technologies in pharmaceutical drug delivery systems (DDSs) are focused on HMW therapeutics — such as proteins and peptides — due to their high specificity and potency.¹ However, HMW substances pose several challenges. For example, peptides and proteins are susceptible to proteolytic degradation and their large, bulky structures make penetrating the skin to reach systemic circulation extremely difficult.²Due to these and other factors, parenteral injection is the most common route of administrating HMW drugs.^3,4

Recognizing the advanced technologies and the potential to meet the needs of unique patients, our PCCA R&D team spent a considerable amount of focused effort exploring new DDS options. In addition to overcoming the challenges of HMW penetration, we also sought to create an anhydrous base with the potential for longer beyond-use dates (BUDs) — which adds greater efficiencies to compounding pharmacies and may improve patient compliance by limiting trips to the pharmacy for medication refills.

After extensive exploration, we concluded that a sublingual route presented an innovative method to deliver HMW compounded medications.

Sublingual Dosage Forms

Sublingual dosage forms are administered under the tongue to deliver drugs rapidly and directly into the systemic circulation by reaching the superior vena cava through the venous drainage located in the external carotid artery (see Figure 1).⁵

Figure 1. Overview of salivary glands shows the SLG (sublingual gland), SMG (submandibular gland) and the external carotid artery.⁶

After selecting the type of base vehicle, we began researching how to facilitate molecular transport through the sublingual mucosa. We quickly realized that the distinct structure and features of micelles mimic human epithelia. As seen in Figure 2, phospholipids with hydrophilic heads and hydrophobic tails form the outer vesicle wall around an aqueous core. We hypothesized that characteristics of the drug molecule could be incorporated into different parts of the micelle.

Figure 2. The phospholipids with hydrophilic heads and hydrophobic tails will self-assemble into this spherical shape when thermodynamic conditions are favorable.⁷

Final Formulation & Testing

Due to the extensive knowledge and skillsets of our R&D team, we formulated a vehicle using carefully chosen ingredients that could self-assemble when interacting with saliva.

While selecting the proper ingredients is an important component in formulation science, developing the right type of micellar structure is even more critical, as it needs to be formulated in such a way that must consider thermodynamic conditions to encourage the formation of these artificial vesicles.

After we felt confident in the formulation, our R&D team conducted tests to verify that all formulation goals were achieved. We conducted a test using fluorescence microscopy, which confirmed that the formulation would indeed create a uniform micellar structure (see Figure 3).⁸

Figure 3. Fluorescence microscopy: GFP 0.1 mg/mL in SubMagna using blue light at 40x magnification. The white arrow indicates the formation of one uniform micelle.⁹

Our R&D team also conducted in vitro testing to understand the potential of HMW molecules penetrating through the sublingual mucosa. The study concluded that SubMagna SL HMW could deliver a peptide into and through the human gingival and oral phenotypic tissues.¹⁰

PCCA members may access the scientific technical report, which contains details of all testing performed on SubMagna SL HMW, after logging on to our Members-Only Website. PCCA members with clinical services access may contact our Clinical Services team to answer any questions about SubMagna, as well as other compounding concerns.

We also invite you to watch our free SubMagna webinar to learn more.

References

Jain K. K. (2020). An Overview of Drug Delivery Systems. Methods in molecular biology (Clifton, N.J.), 2059, 1–54. Accessed February 2024 at https://doi.org/10.1007/978-1-4939-9798-5_1
Lian, Z., & Ji, T. (2020). Functional peptide-based drug delivery systems. Journal of materials chemistry. B, 8(31), 6517–6529. Accessed February 2024 at https://doi.org/10.1039/d0tb00713g
Bajracharya, R., Song, J. G., Back, S. Y., & Han, H. K. (2019). Recent Advancements in Non-Invasive Formulations for Protein Drug Delivery. Computational and structural biotechnology journal, 17, 1290–1308. Accessed February 2024 at https://doi.org/10.1016/j.csbj.2019.09.004
U.S. Food & Drug Administration Center for Drug Evaluation and Research (CBER). 2023 Biological Approvals. Accessed February 2024 at https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/2023-biological-approvals
Hua S. (2019). Advances in Nanoparticulate Drug Delivery Approaches for Sublingual and Buccal Administration. Frontiers in pharmacology, 10, 1328. Accessed February 2024 at https://doi.org/10.3389/fphar.2019.01328
Vining, K.H., Hoffman, M.P. (2014). Anatomy, Biogenesis and Regeneration of Salivary Glands. Monographs in Oral Science 24: 1-13. Open Access Publication. Accessed February 2024 at https://doi.org/10.1159/000358776
Cimino C., Maurel O.M., Musumeci T., et al. (2021). Essential Oils: Pharmaceutical Applications and Encapsulation Strategies into Lipid-Based Delivery Systems. Pharmaceutics 13:327. Open Access Publication. Accessed February 2024 at https://doi.org/10.3390/pharmaceutics13030327
PCCA Science Technical Report (2024). Evaluation of SubMagna™ SL HMW Micellar Formation using Florescence Microscopy. PCCA Document #100069
PCCA Science Technical Report (2024). Evaluation of SubMagna™ SL HMW Micellar Formation using Florescence Microscopy. PCCA Document #100069
PCCA Science Technical Report (2024) Evaluation of the Absorption of a Sublingual Semaglutide Compounded Formulation (SubMagna™ SL HMW) using the EpiGingival™ and EpiOral™ In Vitro Tissue Models. PCCA Document #100068

A Hard Pill to Swallow? A Permeation-Enhancing, Topical Base May Help!

Wed, 06 Mar 2024 16:53:59 GMT

by Beau Harger, PharmD, PCCA Clinical Compounding Pharmacist/Training Instructor

Popular compounds such as transdermal methimazole for hyperthyroidism and transdermal buprenorphine for pain in felines are common in the veterinary world. Not only has this delivery been a staple for pets like cats and dogs, in some instances, this method may be used for some exotic species as well. For example, delivery through the skin has been used under the wing in birds.

Key Considerations

The site of transdermal application is important. The ideal site has a thin stratum corneum with minimal hair follicles, adequate blood perfusion and is difficult for the patient to access (i.e., the pinna in felines and canines).¹ Another key consideration is the selection of the base vehicle. PCCA Lipoderm^® had been the industry-leading base used in permeation-enhancing compounded preparations for many years. While Lipoderm had met the need for an alternative dosing form, the industry was seeking anhydrous options for stability and extended-beyond use dates (BUDs) without compromising the skin-permeation performance.

Innovation Meets Demand

PCCA introduced PermE8^® Anhydrous Gel, an anhydrous, permeation-enhancing base, in 2018. PermE8 is classified as an anhydrous base due to water activity below 0.6 (Aw < 0.6).² Comparison testing between Lipoderm and PermE8 Anhydrous Gel was conducted in vitro using a human skin model that measured the skin percutaneous absorption of ketoprofen. Test results indicated that PermE8 performed comparably to Lipoderm and significantly outperformed Anhydrous Lipoderm^®.^2,3 Traditionally, anhydrous bases didn’t have a smooth feel; however, PermE8 offers a soothing, silky texture that makes application more enjoyable for patients. It was also formulated without preservatives and may be an option for those pets with sensitive skin.

Important Considerations

It’s important for pharmacists and veterinarians alike to understand that not all drugs are good candidates for transdermal delivery.

Important considerations include:

Molecular weight of the drug
Intended use of the preparation
Dosing delivery
If the drug has a narrow therapeutic index (i.e., warfarin, digoxin)
Irritation potential of the drug on the patient’s skin
Risk of drug transference to the caregiver/owner⁴

Drugs with large molecular weights may not pass through the skin and antibiotics could produce low serum levels, resulting in antibiotic resistance. If the veterinarian recommends proceeding with transdermal administration, it is important that monitoring parameters are established to assess the effectiveness of the preparation.

Compounding Tips

When compounding with PermE8, we recommend not exceeding a 20% powder load. This could include the pure API alone or with commercially available drug tablets or capsules containing excipients. Appropriate wetting agents are propylene glycol, diethylene glycol monoethyl ether or ethyl alcohol at a 5-10% concentration. We also recommend using an electronic mortar and pestle (EMP) on a high setting before and after milling to ensure full incorporation of wetting agent and API.

Permeation-enhancing formulations offer options for veterinary patients who otherwise may not receive treatment. Compounding pharmacies that provide these therapies should consider and have access to the newest technology — for people as well as pets — to optimize their influence in their community and in the compounding industry.

PCCA members with clinical services access may contact our Clinical Services team for answers to questions about permeation-enhancing topical preparations, as well as other compounding concerns.

References

Forsythe L. E. (2017). Feline Transdermal Formulation Considerations. International journal of pharmaceutical compounding, 21(6), 446–452.
PCCA PermE8® Anhydrous Gel. PCCA Document #99608.
PCCA (2018) Evaluation of the in vitro Human Skin Percutaneous Absorption of Ketoprofen in PCCA PermE8™ Anhydrous Gel vs. PCCA Lipoderm® PCCA Document #99732.
Eichstadt, L. R., & Davidson, G. S. (2014). To compound or not to compound: a veterinary transdermal discussion. International journal of pharmaceutical compounding, 18(5), 366–369.

Exploring Alternative Avenues for Weight Loss

Wed, 06 Dec 2023 18:47:40 GMT

by Sara Hover, RPh, FAARM, PCCA Director of Clinical Services

Berberine: The Golden Compound

Berberine, a deep-yellow bioactive agent found in several plants like barberry, goldenseal and tree turmeric, has gained attention for its potential role in weight loss.¹ Studies indicate that berberine may influence various metabolic processes, such as promoting insulin secretion, improving insulin resistance, inhibiting formation of fat, alleviating adipose tissue fibrosis, reducing fatty liver disease and improving gut microbiota disorders. The specific mechanism for enhancing insulin sensitivity and regulating blood glucose levels is thought to be by activating AMP-activated protein kinase (AMPK). It is well known that improving glucose control could support weight loss efforts.² In addition to these proposed mechanisms, berberine may influence gut microbiota composition, promoting a balanced and diverse microbial community. A healthy gut microbiome has been recognized as crucial for overall well-being, including weight management.³ The health of the gut continues to be of vital importance.

Alpha-Lipoic Acid: The Antioxidant Ally

Alpha-lipoic acid (ALA) is mainly considered for its role as an antioxidant. It is found naturally in the body and can also be obtained through certain foods and supplements. Some studies suggest that ALA may have a positive impact on weight loss by improving insulin sensitivity and enhancing the utilization of glucose for energy.⁴

ALA has been considered an insulin mimetic agent because of its effects on the insulin-regulated glucose transporter, GLUT4, which is the gatekeeper that allows glucose to enter the cell. However, it is still unclear exactly how ALA interacts with the insulin receptor and insulin receptor cascade. It is possible that ancillary effects of ALA on mitochondria can improve insulin sensitivity. In addition to the insulin-like effect of glucose transport, some evidence suggests that it also acts on beta-cells.4 Additionally, ALA as a powerful antioxidant may help reduce oxidative stress and inflammation, contributing to an overall healthier metabolic environment. More research is needed to fully understand ALA's role in weight management, but initial findings are promising.⁴

Oxytocin: The "Love It or Leave It Hormone"

Oxytocin, often referred to as the "love hormone" or "bonding hormone," is primarily associated with social bonding, childbirth and lactation. Recent research has explored its potential role in weight regulation and appetite control. Oxytocin is a hormone peptide of nine amino acids produced by neurons in the hypothalamus, secreted directly into brain regions involved in energy homeostasis and appetite regulation, and released into the bloodstream by the posterior pituitary gland.⁵

Oxytocin affects appetite by decreasing intake and promoting the breakdown and oxidation of fats. It also increases thermoregulation and energy consumption. It may also play a role in glucose and metabolic homeostasis, which can improve insulin sensitivity.⁶

Oxytocin decreases food intake by affecting hedonic eating, which is one's desire or drive to consume food for pleasure, in the absence of caloric need. It can also cause satiety signaling in the brain. A positive relationship was found between oxytocin levels, body mass index, visceral fat mass and metabolic syndrome.⁶ Some studies suggest that oxytocin may help reduce overall food consumption, especially in response to stress-induced eating. While oxytocin is not yet widely used as a weight-loss agent, ongoing research is needed to uncover its potential applications.

Topiramate: The Antiepileptic Agent with a Possible Bonus

Originally developed as an antiepileptic medication, topiramate has also shown promise in the field of weight management. Although the mechanism behind topiramate-induced weight loss is not well described, a possible mechanism includes lowering calorie intake, decreasing fat gain, triglycerides and cholesterol levels. A study reported the possibility that topiramate reduces binge-eating behavior by altering the reward pathway associated with the food. A reduction in leptin levels was seen while patients were on topiramate, which directly correlated with weight reduction.⁷

Clinical trials have demonstrated that topiramate can lead to significant weight loss in certain individuals, particularly when used in combination with other weight loss strategies. However, it's essential to note that topiramate can have side effects, and its use should be supervised by a healthcare professional.

Approach with Caution

While berberine, alpha-lipoic acid, oxytocin and topiramate show promise as alternative options for weight loss, it's crucial to approach these agents with caution. Before incorporating any new supplement or medication into a weight loss regimen, it's advisable to consult with a healthcare professional. Additionally, these alternatives should complement, not replace, a healthy diet and regular exercise. As research continues to unravel the complexities of these agents, the potential for innovative and personalized approaches to weight management grows. Always stay informed and work closely with healthcare providers to make informed decisions on your weight loss journey.

References

Neag M.A., Mocan A., Echeverría J., et al. (2018) Berberine: Botanical Occurrence, Traditional Uses, Extraction Methods, and Relevance in Cardiovascular, Metabolic, Hepatic, and Renal Disorders. Front Pharmacol. 9:557. Accessed November 2023 at https://doi: 10.3389/fphar.2018.00557
Xu X., Yi H., Wu J., et al. (Epub 2020) Therapeutic effect of berberine on metabolic diseases: Both pharmacological data and clinical evidence. Biomed Pharmacother. 133:110984. Accessed November 2023 at https://doi: 10.1016/j.biopha.2020.110984
Zhang L., Wu X., Yang R., et al. (2021) Effects of Berberine on the Gastrointestinal Microbiota. Front Cell Infect Microbiol. 10:588517. Accessed November 2023 at https://doi: 10.3389/fcimb.2020.588517
Capece U., Moffa S., Improta I., et al. (2022) Alpha-Lipoic Acid and Glucose Metabolism: A Comprehensive Update on Biochemical and Therapeutic Features. Nutrients. 15(1):18. Accessed November 2023 at https://doi: 10.3390/nu15010018
Wronski M.L., Plessow F., Kerem L., et al. (2022) A randomized, double-blind, placebo-controlled clinical trial of 8-week intranasal oxytocin administration in adults with obesity: Rationale, study design, and methods. Contemp Clin Trials. 122:106909. Accessed November 2023 at https://doi: 10.1016/j.cct.2022.106909
Hong S.M., Ko J.K., Moon J.J., et al. (2021) Oxytocin: A Potential Therapeutic for Obesity. J Obes Metab Syndr. 30(2):115-123. Accessed November 2023 at https://doi: 10.7570/jomes20098
Wajid I., Vega A., Thornhill K., et al. (2023) Topiramate (Topamax): Evolving Role in Weight Reduction Management: A Narrative Review. Life (Basel). 13(9):1845. Accessed November 2023 at https://doi: 10.3390/life13091845

Mutual Purpose. Shared Innovation.

Wed, 29 Nov 2023 22:20:07 GMT

Mutual Purpose. Shared Innovation.

by Mark Gonzalez, PharmD, PCCA Clinical Compounding Pharmacist

Your “purpose” to help patients and providers is what motivates us to innovate, create, test, formulate and introduce new bases.

Behind every new base and subsequent formulation development, our purpose is to help you create in the lab, help patients and providers in new and exciting ways, and ultimately strengthen the relationships you have worked so hard to build and maintain.

Our revolutionary new base, EctoSeal P2G, is no exception in our purpose to serve you, your patients and prescribers.

CREATE

EctoSeal P2G is one of the first bases in the industry to combine a variety of clinical applications with three different dosage forms: topical powder, topical powder for reconstitution and topical hydrogel. The flexibility that comes with this base is unparalleled.

EctoSeal P2G can be mixed with a variety of active pharmaceutical ingredients (APIs) that, after dispensing and at time of use, can be insufflated — or sprinkled —directly onto a wound. Dispensing in a topical powder dosage form provides the potential for longer beyond-use dates for your pharmacy and convenience for your patients. The topical powder dosage form absorbs the exudate of wet wounds and quickly transforms into a hydrogel that, as it dries, forms a protective film that may help APIs better adhere to the wound bed. In addition, the protective film can potentially secure a moistened environment.

For dry wounds, the powder can be applied directly to the wound and moistened with purified water, sterile water or saline to induce the film-forming effect. The topical powder application is helpful with larger, deeper wounds, and also has excellent application for common abrasions, burns and exudative, eruptive sites of infection.

EctoSeal P2G can also be dispensed as a topical powder for reconstitution, where the powder is mixed with appropriate API(s), brought to volume (q.s.) with maltodextrin and dispensed in a jar. At time of use, the compounded preparation is measured in level scoops and placed in a medicine cup. Purified water, sterile water or saline is then added, and the preparation is mixed by hand for about 15 seconds to create a hydrogel, which is then applied to the affected area. When dispensed as a powder for reconstitution, most EctoSeal P2G compounds can be assigned a BUD of 180 days.

Dispensing as a topical hydrogel dosage form is another option. To dispense as a topical hydrogel, the EctoSeal P2G powder is first mixed with relevant APIs, then with an appropriate wetting agent, preservative and purified water. When dispensed as a hydrogel, the BUD should not exceed more than 14 days if unpreserved.

Regardless of dosage form, when moistened, EctoSeal P2G forms a strong yet pliable film as it dries. The protective film may provide longer-term delivery of APIs. In addition, the preparation develops a mostly clear thin film as it dries, allowing a protective, moist environment recognized to help wound healing. Even better, EctoSeal P2G easily reverts from a film to a gel when remoistened, making wound cleaning easier and less painful for patients.

HELP

As soon as I was introduced to this base during pre-launch discussions, my mind began to race with all of the potential applications and how they would be able to help patients, as well as help practitioners prescribe a potentially more efficacious, patient-friendly and environmentally-friendly option. Specialties such as:

Wound care
Post-surgical care (e.g., initial care of suture sites)
Hospice
Geriatrics
Dermatology (e.g., acne, warts, infections, hidradenitis supurativa)
Pediatrics
Podiatry (e.g., onychomycosis, ingrown toenail pain relief)
Proctology (e.g., external hemorrhoids/fissures)
Veterinary

Strengthen

You became a compounder with the objective of being able to create preparations, help patients and strengthen your relationships with patients and providers. EctoSeal P2G is an exciting way to reignite those initial passions or flame your passions as a novice compounder.

Don’t let EctoSeal P2G be another base that you wait years to use. Take advantage of its versatility, ease of application and the potential promise to help you solve some of the most common medical issues confronting patients, providers and your pharmacy. Experience EctoSeal P2G today to create topical preparations, help your patients and build relationships with prescribers within your community. Members with clinical service access may contact the Clinical Services team for additional help with EctoSeal P2G or other compounding concerns.

Tune in to the Mortar & Pestle podcast to hear PCCA Chief Scientific Officer Gus Bassani and PCCA Director of Research and Development Daniel Banov discuss the science behind our revolutionary new base.

A complete version of this article originally appeared in PCCA’s members-only magazine, the Apothagram.

ThinkNext: International Seminar 2023

Wed, 08 Nov 2023 17:41:02 GMT

ThinkNext: ISTX23, the must-see compounding event held October 26-28 at The Woodlands Waterway Marriott, was our best International Seminar ever — until next year!

Day 1: Pearls from the Mainstage

ThinkNext: ISTX23 kicked off with a lively presentation from Peter Lovatt, PhD, also known as “Dr. Dance.” Dr. Lovatt discussed how structured and improvised movements affect brain functions, reviewed clinical studies on how structured dance movements positively impact people with Parkinson’s disease and, at the end of his presentation, encouraged the audience to participate in a structured dance routine.

PCCA Director of Research & Development Daniel Banov, RPh, MS, introduced our new base, EctoSeal P2G™ Powder, developed to transform wound care preparations at the tissue level. As Daniel discussed the benefits of the base’s natural ingredients, audience members received samples of EctoSeal P2G to see how it quickly transforms from powder to hydrogel and experience, firsthand, its protective film.

Our Member Pearls Panel started with Eddie DeCaria, RPh, FAPC, who presented ways to retain pharmacy staff and ensure they, as well as your pharmacy, thrive. Robyn Crow, RPh, followed with tips on dermatology compounding, and Jennifer Palazzolo, RPh, closed the session by discussing how point-of-care services can increase your pharmacy revenues.

After the Rx Runway Fashion Show lunch featuring 11 compounding colleagues sharing clinical compounding and business tips, participants heard from Sarah Zielsdorf, MD, MS, who shared her personal, “strenuous journey” on infertility during Part 1 of the Infertility Triad. Her pearl: “Test. Don’t guess.” Part 2 featured PCCA Director of Clinical Services Sara Hover, RPh, FAARM, who presented new infertility information, including endocrine disruptors, how mitochondria are involved in embryogenesis and nutrients that support mitochondria. Sara’s pearl: “Think of your patient’s’ hormone levels as a vital sign.” Part 3 of the triad featured a review of patient Margie Lamberth’s powerful story about her own infertility journey, which resulted in the birth of her son.

The final discussion of the day by our Regulatory Panel addressed topics ranging from GFI #256 to USP 800 implementation. The Regulatory Panel’s pearl: “Get involved. Get your patients involved. All of you are constituents.” Day 1 concluded with Ashley Berthelot of Professional Arts Pharmacy in Lafayette, Louisiana, receiving our 2023 L. David Sparks Advocacy award.

Watch the dance moves and see what you missed by clicking the video.

Day 2: Workshops Aplenty & Celebration

Rep. Morgan Griffith (R-VA) started the day sharing how two generations of his family were positively impacted by his local compounding pharmacy. Rep. Griffith later discussed why he introduced HR 167, the “Patient Access to Urgent-Use Pharmacy Compounding Act of 2023,” which in part addresses how compounders can help resolve drug shortages. His pearl: “Get to know your congressional members before issues arise.”

Participants later attended their choice of workshops from more than 15 options across five different tracks. For example, a Clinical & Formulations workshop offered “Top 10 Compounding Tips from the Lab”; a Marketing & Sales workshop presented “Do This, Not That: Making Claims and Images on Social Media”; and a Business & Development workshop discussed, “Pharmacy Talent Management: Nurturing the Best, Releasing the Rest.”

In between workshop sessions, participants enjoyed the Awards Luncheon, where we presented our 2023 M. George Webber Compounding Pharmacist of the Year award to Kevin Borg, PharmD, FAPC, FACA, owner of Potter’s House Apothecary in Peoria, Arizona, and Prescott Compounding Pharmacy in Prescott, Arizona. Our 2023 George Roentsch New Innovator award was also presented to Dayna Timmer, PharmD, owner of Mountainside Compounding in Tate, Georgia.

Day 2 ended with a party celebrating compounders and PCCA CEO David Sparks’ 80th birthday. Attendees dressed in their favorite 1950s attire, then danced, ate and partied like it was 1955!

Relive the fun or see what you missed in this short video.

Day 3: More Learning, Networking & Fun

The morning opened with functional medicine practitioner Mary Caire, MD, who covered “Emerging Therapies: Protocols for Low-Dose Naltrexone (LDN), Methylene Blue and Ivermectin.” During her presentation, Dr. Caire discussed how LDN tricks the brain into producing more endorphins. PCCA Clinical Compounding Pharmacist Sebastian Denison, RPh, FAARM (candidate), then tag-teamed Dr. Caire for a deeper dive into the chemical aspects of LDN, methylene blue and ivermectin, and ended his presentation by expressing his enthusiasm for how these emerging therapies may help patients.

Next, Holly Seyler, winner of our 2023 PCCA Institute Pharmacy Student Scholarship, treated participants to an enthusiastic presentation on “Speaking Loudly and Boldy for Our Patients” and thanked her compounding colleagues for their amazing support.

The day concluded with the return of Dr. Caire, whose presentation, “Libido is Your Life Drive,” explored the connection between libido, hormones and health, explaining how the libido is impacted by declining hormone levels, which

in turn may lead to declining health as we age.

Throughout the 3-day event, participants also enjoyed catching up with compounding colleagues, networking and enjoying the many activities of the new venue. We hope to see even more PCCA members, old and new, at ThinkNext: ISTX24 — our next “best international seminar ever!”

Catch a glimpse of what’s in store for ThinkNext: ISTX24.

Backed by Science - SuspendIt® Anhydrous

Wed, 22 Mar 2023 12:23:07 GMT

by Maria Carvalho, PharmD, MRPharmS, PhD, Manager of PCCA Science (R&D) and Yi Liu, PharmD, PhD, RPh, PCCA Research Pharmacist

Our new, patent-pending base — SuspendIt Anhydrous — is an innovative anhydrous suspension vehicle that offers improved physical characteristics, broader application and the potential for longer default beyond use dates (BUDs). It is ideal for active pharmaceutical ingredients (APIs) that are unstable in water or have incompatibilities with existing aqueous vehicles.

We performed multiple tests, including evaluation of SuspendIt Anhydrous’ sedimentation properties, its self-emulsifying drug delivery system and compatibility with nasogastric feeling tubes, as summarized below.

Improved Physical Characteristics

A unique physical characteristic of SuspendIt Anhydrous is its improved viscosity, which reduces when shaken and thickens when standing. The improved viscosity allows for rapid redispersion of APIs with agitation and minimizes sedimentation. Sedimentation is the simple process in which suspended particles separate from a liquid and, due to gravity, settle on the bottom of a container.

In one of three studies, we evaluated and compared the sedimentation properties of SuspendIt Anhydrous to the performance of two competitor products (Product A and Product B) using an enrofloxacin 100 mg/mL anhydrous suspension (raspberry flavor, pink color). The suspensions were placed in a standing position at room temperature for 30 days. On day 28, the glass containers were shaken vigorously with the same amount of force and duration and allowed to settle again. By day 29 (after redispersion on day 28), SuspendIt Anhydrous remained a homogenous suspension with no signs of separation (Figures 1 – 3).

Self-Emulsifying Drug Delivery System

What makes our new base particularly unique is its self-emulsifying drug delivery system (SEDDS). The system creates a spontaneous emulsion when SuspendIt Anhydrous comes into contact with water or other liquids, creating a uniform emulsion that is characterized by small and homogenous droplets.

In one of two studies, we conducted a microscopic evaluation of droplet size formation for metronidazole 50 mg/mL anhydrous suspension prepared using SuspendIt Anhydrous (left) and Product B (right). When the samples were observed under the microscope at 4x magnification, the suspension using the PCCA SuspendIt Anhydrous showed a homogeneous dispersion (Figure 2). Product B displayed aggregation of metronidazole (Figure 3, highlighted with arrow) and separation of the water and oily phases (Figure 4, highlighted with arrow).

Figures 2-4.Microscopic evaluation of droplet size formation (4x objective lens) for metronidazole 50 mg/mL anhydrous suspension prepared using SuspendIt Anhydrous (left) and Product B (right).

The SEDDS in SuspendIt Anhydrous allows for the formation of a uniform emulsion, characterized by small and homogeneous droplets. As a result, the self-emulsifying properties of SuspendIt Anhydrous are likely to promote increased drug solubility, dispersibility, absorption and bioavailability.

Compatible with Nasogastric Feeding Tubes

Nasogastric feeding tubes are commonly used in patients when enteral nutrition is required. However, tube clogging remains a significant barrier to the delivery of drug and nutritional support — attention must always be paid to this potential complication. It is also essential that drug administered via a nasogastric tube preserves the correct API dose when exiting from the tube.

In one of several of studies, we evaluated the likelihood of compounded anhydrous suspensions (metronidazole 50 mg/mL, tretinoin 10 mg/mL or nifedipine 4 mg/mL) to block or leave residues in nasogastric feeding tubes. The resulting volume was measured; potency testing was determined by HPLC. Results indicated the amount of metronidazole, tretinoin or nifedipine recovered from the feeding tubes was >95% for SuspendIt Anhydrous.

Figure 1. Note how the SuspendIt Anhydrous formulation flows freely and does not cause clumping or blockage. Click the image to watch the video.

On the day after the recovery test, we observed that there were no significant drug residues throughout the nasogastric tube, nor at the exit of the tube, for the oral suspensions in SuspendIt Anhydrous (Figure 2). On the contrary, there was visible accumulation of drug residues for the corresponding Product A and Product B oral suspensions, which suggests potential tube clogging (Figures 3 and 4).

Figures 2-4. Nasogastric feeding tubes (exit) on the day after the recovery test for the metronidazole oral suspensions in PCCA SuspendIt Anhydrous and the corresponding Product A and Product B products.

To view details of the multiple studies conducted using SuspendIt Anhydrous, PCCA members can access the complete Science Manual on our Members-Only Website. PCCA members also have access to formulas developed for SuspendIt Anhydrous, including stability studies. Members with clinical services may contact our Clinical Services Team for help with formulas and other compounding concerns.

Recent Product Development, Clinical Research and Formulation Studies from PCCA

Wed, 04 Aug 2021 13:34:56 GMT

By Gus Bassani, PharmD, PCCA Chief Scientific Officer

The last 18 months were unique and challenging to say the least. Despite the pandemic and the disruption it caused, I am incredibly proud of our Research and Development (R&D), Formulation Development, PCCA Science and Clinical Services teams’ accomplishments.

We were able to advance several ongoing R&D projects related to new products, clinical research and formulation studies, while seamlessly continuing to field our member pharmacies’ technical questions via our decentralized Clinical Services team. Our scientists remained in the labs and separated into split shifts to mitigate risk. This all resulted in us getting a lot done in the face of significant uncertainty!

With much excitement, last year we finalized development and launched our new product, Ellage^®, an anhydrous vaginal base with mucoadherent and self-emulsifying properties, giving compounders the ability to extend beyond-use dates (BUDs) and provide better delivery and adhesion to the vaginal mucosa. Feedback on this new delivery system has been incredibly positive.

Because of the pandemic, you may not be aware that our PCCA Science team published a terrific clinical study evaluating the efficacy of dexamethasone in our base MucoLox^™ as a treatment for oral lichen planus (OLP). The study was supported by PCCA and performed through the Division of Oral Medicine & Dentistry at Brigham & Women’s Hospital in Boston as well as the Harvard School of Dental Medicine. It was published in the widely read journal Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology. The study concluded that “a dexamethasone 0.1 mg/mL solution in MucoLox was more effective for the management of OLP compared with the commercial dexamethasone 0.1 mg/mL solution.”¹ A follow-up study is now underway with the same principal investigator at the University of California, San Francisco, looking at the impact of this MucoLox preparation on oral inflammatory ulcerative diseases. There is also an ongoing MucoLox study being conducted by the Levine Cancer Institute in North Carolina, which is focused on oral mucositis. The ultimate goal of these studies is to generate data that will benefit patients and show the value that pharmacy compounding can bring to patients with these conditions.

Our Formulation Development team grew our library of BUD studies under the FormulaPlus^™ umbrella, finalizing 26, many of which were bracketed. This past year, our dedicated team of scientists created 307 new formulas and revised 3,959, adding significant value for PCCA members. This is an impressive feat, especially in light of the pandemic conditions.

Behind the scenes, PCCA R&D has been in the process of changing several of our bases’ preservative systems in response to growing preferences regarding the avoidance of methylisothiazolinone in topical products. We completed this work on VersaBase^® Cream last year, which was a huge multi-year undertaking, since we had to reperform all of the associated BUD studies in addition to the extensive numbers of microbiological tests. As consumer and practitioner preferences change, we must adapt as well. The R&D team has done a wonderful job navigating this project.

The PCCA innovation pipeline is currently full of projects and research intended to make a difference in patients’ lives, and to put pharmacists in a better position to maintain an active role in personalized medicine. The world of pharmaceutical compounding has seen an abundance of change, but there are still patient needs unmet by commercially available options. Additionally, the science surrounding pharmacogenomics, metabolomics and biomarkers-of-response is accelerating the development of therapies that are precise and individualized. We envision pharmacists who are trained in compounding and equipped with the necessary formulation technology to be a critical component of providing these therapies in the future. With this vision in mind, our scientific teams are keeping their “hands on the plow” and pushing forward with purpose!

Also on The PCCA Blog: USP-NF and U.S. Pharmacist Featuring Proprietary PCCA Bases

Gus Bassani, PharmD, PCCA Chief Scientific Officer, has been with PCCA since September 2002. Prior to that, he was a formulation pharmacist in the product development lab of a veterinary pharmaceutical company. He has worked in multiple pharmacy practice settings in Alaska, Iowa and Kansas, and has taught extemporaneous compounding principles to pharmacy students in Drake University's Pharmaceutics Laboratory course. Gus earned his Doctor of Pharmacy degree from the Drake University College of Pharmacy and Health Sciences. He is a member of the 2020–2025 United States Pharmacopeia Compounding Expert Committee, and has been on the committee since 2010. He served on the 2012–2014 Drake University College of Pharmacy and Health Sciences National Advisory Council. He is a member of the American Pharmacists Association (APhA), Alliance for Pharmacy Compounding (APC), American Association of Pharmaceutical Scientists (AAPS) and National Community Pharmacists Association (NCPA).

Reference

1. Villa, A., Sankar, V., Bassani, G., Johnson, L. B., & Sroussi, H. (2020). Dexamethasone solution and dexamethasone in MucoLox for the treatment of oral lichen planus: A preliminary study.Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 129(6), 585–590. https://doi.org/10.1016/j.oooo.2020.02.014

The Science behind Ellage™ Anhydrous Vaginal Base

Wed, 20 Jan 2021 13:52:11 GMT

By Maria Carvalho, PharmD, MRPharmS, PhD, Manager of PCCA Science

PCCA’s Research and Development department is committed to developing the most effective, innovative and functional products for the compounding industry. In that spirit, we invest significant time and resources to the study and validation of our technology. Our newest base, Ellage, is no exception. That’s why we are proud and excited to give you an in-depth look at the science behind the first ever anhydrous compounding base developed specifically for the vaginal delivery of medications.

1. The Science behind the Innovation in Ellage

A key innovative property of Ellage is its self-emulsifying drug delivery system, which has the potential to maximize drug solubility and bioavailability. Upon microscopic evaluation, we observed that Ellage developed droplets when mixed with a vaginal fluid simulant (VFS), and these droplets decreased in size between 1–5 minutes of incubation at 98.6° F (37° C). This is the process of self-emulsifying, and we observed it as well in the presence of active pharmaceutical ingredients (APIs) and small amounts of VFS. On the contrary, PCCA Plasticized^™ (an anhydrous gel base) did not mix with VFS at all. VersaBase^® Cream (an emulsifying cream base) made a homogeneous emulsion, but the size of the droplets remained unchanged.¹

Using fluorescence microscopy, we also observed that hydrophilic and lipophilic substances exhibit a different distribution pattern when Ellage is mixed with VFS. Fluorescein sodium (hydrophilic) and curcumin (lipophilic) were evenly distributed in Ellage alone, but when the spontaneous emulsion was created from contact with VFS, the curcumin was encapsulated inside the droplets, whereas the fluorescein sodium remained in the continuous aqueous phase.²

Another key innovative property of Ellage is its advanced mucoadhesion, which has the potential to increase the contact time between the APIs and the vaginal mucosa. We performed in vitro and ex vivo tests on Ellage to evaluate its leakage potential and mucoadhesive properties. We used an over-the-counter (OTC) vaginal moisturizer, which claims to be long-lasting (up to three days), for comparison purposes in these tests. Results from the leakage test show that Ellage alone and in PCCA formulas with amitriptyline 2% and baclofen 2% as well as estriol 0.1% and testosterone 0.1%, respectively, have high retention potential in vitro, superior to the OTC product.³

Likewise, testing on animal vaginal tissues demonstrates that Ellage and the well-established combination of MucoLox^™/VersaBase Gel (50:50) exhibit prolonged mucoadhesion, superior to the OTC product. ⁴ Our bioadhesion testing using a texture analyzer also demonstrates that Ellage has a good bioadhesion profile, similar to MucoLox/VersaBase Gel (50:50) as well as the OTC product.⁵

The Clinical Significance of the Innovation

For compounding pharmacists, these results are clinically significant because Ellage is expected to exhibit its self-emulsifying properties even in the presence of small amounts of vaginal fluid, such as one would expect with cases of vaginal dryness. In addition, lipophilic APIs are expected to exhibit a slow drug release whereas hydrophilic APIs are expected to exhibit a fast drug release from Ellage.

In clinical practice, custom medications compounded with Ellage are also expected to adhere to the vaginal mucosa for a long period of time, despite the secretion of vaginal fluid, because of its prolonged mucoadhesion properties.

2. The Science behind the Quality & Safety of Ellage

An important consideration for any base used in a vaginal compound is its effect on the mildly acidic vaginal pH (≈4.5). To verify whether Ellage affected pH, we prepared a VFS with a pH of 4.54 and placed it in a water bath at 98.6° F (37° C). We added Ellage to increasing volumes of the VFS and measured the pH of the resulting solutions in duplicate. The pH ranges we obtained (4.51–4.645) demonstrate that Ellage did not significantly change the baseline pH of the VFS.⁶

Another important consideration of a vaginal base is its potential to irritate tissue, so we tested Ellage to determine that it is nonirritating to the vaginal mucosa as well. We used the in vitro hen’s egg test – chorioallantoic membrane (HET-CAM) assay, which measures the ability to induce toxicity in the CAM of a chicken egg, to test the ocular/vaginal irritation potential of Ellage in comparison to positive and negative controls. Our test preliminary test demonstrated that Ellage has no ocular/vaginal irritation potential (irritation score <5), and it was confirmed by an outsourced study by the Consumer Product Testing Company in Fairfield, New Jersey.⁷

Additionally, we evaluated the safety and toxicological profile of Ellage using the MTT effective time 50 (ET₅₀) in vitro assay, which consists of measuring the reduction of MTT (3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide) by the viable cells in the EpiVaginal^™ tissue model. Following 24 hours of exposure to Ellage, the viability of the cells was 78%, as opposed to less than 3% after exposure to the spermicide Gynol II, which was the negative control. We obtained similar results for two reference OTC vaginal lubricants used as positive controls in this study.⁸

The Clinical Significance of the Quality & Safety

These findings show that Ellage should not affect vaginal pH, and it is expected to be nonirritating for vaginal tissue, which helps compounding pharmacists to ensure the quality and safety of their formulations that contain this base.

3. The Science behind the Efficacy of Ellage

As we developed this base, we knew that it must be effective at delivering APIs to vaginal tissue, so we evaluated its drug-release performance. We prepared a VFS and used it as the receptor medium in the Franz diffusion system to evaluate the in vitro drug release of amitriptyline 2% and baclofen 2% in Ellage versus VersaBase Cream as well as estriol 0.1% and testosterone 0.1% in Ellage versus VersaBase Cream. The results show that the amount of amitriptyline 2% and testosterone 0.1% released from VersaBase Cream was higher at all time points in the studies compared to Ellage. On the other hand, the amount of baclofen 2% and estriol 0.1% released from Ellage was higher at all time points in comparison to VersaBase Cream. These two comparative studies were not designed to evaluate any statistical differences between these two bases and are not intended to predict in vivo performance. However, they do show that Ellage has comparable in vitro performance to VersaBase Cream.^9,10

The Clinical Significance of the Efficacy

These in vitro studies are important for compounding pharmacies to ensure comparable release profiles when drugs are incorporated in the newly developed Ellage versus the well-established VersaBase Cream.

For detailed information on the science behind Ellage Anhydrous Vaginal , please consult the corresponding technical reports at pccarx.com/science. PCCA members can also contact us at PCCAScience@pccarx.com.

Maria Carvalho, PharmD, MRPharmS, PhD, is the Manager of PCCA Science. She is a certified pharmacist in Portugal and the United Kingdom with a PhD in pharmaceutical compounding from the University College of London (UCL). Maria has worked in community pharmacy, hospital pharmacy and the pharmaceutical industry in Europe and the United States. She was a teaching assistant at the UCL School of Pharmacy (UK) and an invited teacher at the University Fernando Pessoa (Portugal). Maria has authored and co-authored many scientific publications, including the book Compounding Practices in Europe (ISBN-10:149236925X).

References

1. PCCA Science. (2020). Evaluation of the self-emulsifying properties of PCCA Ellage part 1: Microscopic evaluation [PCCA Document #99838]. http://beta.pccarx.com/pdf_files/PCCA%20Science/Technical%20Reports/99838_TR_Ellage-Self-EmulsProp-Part1.pdf

2. PCCA Science. (2020). Evaluation of the self-emulsifying properties of PCCA Ellage part 2: Fluorescence microscopy [PCCA Document #99839]. http://beta.pccarx.com/pdf_files/PCCA%20Science/Technical%20Reports/99839_TR_Ellage-Self-EmulsProp-Part2.pdf

3. PCCA Science. (2020). The leakage test: Evaluation of the leakage potential of PCCA Ellage [PCCA Document #99816]. http://www.pccarx.com/pdf_files/99816_TR_EllageLeakageTest.pdf

4. PCCA Science. (2020). Evaluation of the mucoadhesive properties of PCCA Ellage part 2: Ex vivo testing on animal vaginal tissues [PCCA Document #99837]. http://beta.pccarx.com/pdf_files/PCCA%20Science/Technical%20Reports/99837_TR_Ellage-MucoadhAnimalTissue-Part-2.pdf

5. PCCA Science. (2020). Evaluation of the mucoadhesive properties of PCCA Ellage part 1: Ex vivo bioadhesion testing using a texture analyzer [PCCA Document #99836]. http://beta.pccarx.com/pdf_files/PCCA%20Science/Technical%20Reports/99836_TR_Ellage-MucoadhTexture-Part-1.pdf

6. PCCA Science. (2020). Effect of Ellage and other PCCA proprietary bases on the pH of vaginal fluid [PCCA Document #99815]. http://www.pccarx.com/pdf_files/99815_TR_Ellage-VaginalpH.pdf

7. PCCA Science. (2020). Evaluation of the irritation potential of PCCA Ellage Anhydrous Vaginal part 1: Hen’s egg test-chorioallantoic membrane assay [PCCA Document #99817]. http://www.pccarx.com/pdf_files/99817_TR_Ellage-Irritation-Part-1.pdf

8. PCCA Science. (2020). Evaluation of the irritation potential of PCCA Ellage Anhydrous Vaginal part 2: Safety and toxicological profile by the MTT assay [PCCA Document #99818]. http://www.pccarx.com/pdf_files/99818_TR_Ellage-MucosalToxic-Part-2.pdf

9. PCCA Science. (2020). In vitro drug release of estriol 0.1% and testosterone 0.1% from VersaBase Cream and PCCA Ellage Anhydrous Vaginal [PCCA Document #99823]. http://beta.pccarx.com/pdf_files/PCCA%20Science/Technical%20Reports/99823_TR_Ellage-DrugRelease-E3-Test.pdf

10. PCCA Science. (2020). In vitro drug release of amitriptyline 2% and baclofen 2% from VersaBase Cream and PCCA Ellage Anhydrous Vaginal [PCCA Document #99824]. http://beta.pccarx.com/pdf_files/PCCA%20Science/Technical%20Reports/99824_TR_Ellage-DrugRelease-AmitrBaclof.pdf

Why Did PCCA Choose FlackTek?

Wed, 02 Dec 2020 13:43:00 GMT

By PCCA

In 2020, PCCA teamed up with FlackTek to become the exclusive distributor of their mixer in the pharmacy industry. This advanced mixing machine offers compounding pharmacies the ability to prepare a variety of different materials efficiently and effortlessly, often with no cleanup required. This means more consistent, reproducible, high-quality compounded creams, gels, suspensions, powders and more in less time, with less effort. And because it uses a closed mixing system, the FlackTek mixer reduces pharmacy compounders’ exposure to chemicals compared with traditional mixing methods. But there’s even more to this incredible machine. Here’s why we chose to offer it to pharmacies along with a breakdown of just how much time you can expect to save when compounding various types of preparations with it.

Why did PCCA choose FlackTek?

The overall technology used by FlackTek is similar to some other mixing machines available to pharmacy compounders: It is a bladeless mixing system that uses a dual, asymmetric centrifuge. It works by spinning a high-speed mixing arm in one direction while the mixing container rotates in the opposite direction. However, PCCA has tested different mixers over the last several years, and the FlackTek mixer stood out from other machines for several reasons:

The mixer is robust; manufactured very well with high-quality materials; and will stand up to heavy, long-term use
FlackTek is known to have very good technical support for their products
The FlackTek mixer is a good size for general pharmacy compounding
It does not need a counterbalance to mix materials like some other compounding mixers, which makes operation much easier and more efficient

These factors are in addition to many other benefits that the FlackTek offers.

How much time can FlackTek save you in the lab?

As mentioned above, the FlackTek mixer can help your pharmacy be more efficient. Our Formulation Development team has been working with it for a while, and they noticed that it can save a lot of time in the compounding lab for a variety of compounded dosage forms. To see just how much, they prepared several different types of compounds and also prepared them using conventional mixing methods. The results were astonishing. You can see them in the infographic below. You can also see the FlackTek mixer in action by visiting our online product catalog.

What does PCCA add to FlackTek?

PCCA’s knowledge and experience with compounded formulations add even more of an advantage to FlackTek’s great product and support. We developed over 30 formulas that use this machine, and PCCA members with Clinical Services support can access them in our formula database . These formulas have all undergone content uniformity testing to ensure reproducible results when using PCCA chemicals and following the specific compounding procedures indicated in the formulas. Additionally, members with Clinical services access can contact us with any formulation questions they may have. This support saves time and lowers the upfront cost of adopting this compounding mixer in your pharmacy.

4 Reasons to Use Ellage™ Anhydrous Vaginal Base in Your Compounding Pharmacy

Wed, 18 Nov 2020 13:47:00 GMT

By PCCA

We debuted our innovative compounding base Ellage Anhydrous Vaginal at the virtual International Seminar 2020. This proprietary PCCA base is the first anhydrous vehicle in the pharmacy compounding industry that was developed specifically for vaginal use. Ellage was designed to be gentle on vaginal tissue, release drugs and keep them in contact with the mucosal surface — all while providing a pleasant experience for patients with various health challenges who need compounded vaginal medication.

Ellage Anhydrous Vaginal is made of pharmaceutical-grade ingredients, all of which are used in FDA-approved drug products, and it has several characteristics that make it a promising new tool that compounding pharmacies can use to meet the needs of patients. Here are our top four reasons why you should try it in your pharmacy:

1. Ellage has significant potential to minimize the leakage of vaginal medication.

A common complaint for vaginal creams and gels is that they are messy and tend to leak. That’s why our Research and Development (R&D) team set out to create a compounding base that would provide customized medications without this drawback. The PCCA Science team, which is part of our R&D department, also assessed this product to see how well it would perform in that regard. In an in vitro leakage test , they applied two Ellage formulations to agar plates tilted at a high angle to see if the preparations would run down the plates — neither one did, even when diluted with synthetic vaginal fluid. This test shows that Ellage Anhydrous Vaginal is likely to adhere to vaginal tissue for a long period of time without leakage or messiness, despite vaginal secretions. Therefore, it may provide a much better medication experience for patients.

2. Ellage is nonirritating and doesn’t affect vaginal pH.

Our R&D team developed Ellage to be very gentle on vaginal tissue, and PCCA Science has conducted two in vitro tests to prove it’s just that. One irritation test assessed how Ellage affected a membrane within a hen’s egg, which is considered more sensitive than human vaginal tissue. Another irritation test evaluated its effect on EpiVaginal^™ tissue, which mimics vaginal mucosal tissue. These tests revealed that Ellage is nonirritating and that it is as mild as two over-the-counter vaginal lubricant products.

The PCCA Science team also assessed how the base affected the pH of a synthetic vaginal fluid. The results of this in vitro test show that Ellage does not affect vaginal pH. However, please note that ingredients incorporated into Ellage may affect the pH.

3. You can use Ellage with a wide variety of active pharmaceutical ingredients (APIs).

PCCA’s R&D team developed Ellage to be versatile so that it could allow compounders to make better customized vaginal medication for each and every woman. That’s why Ellage can accommodate a wide variety of APIs, including hormones, antimicrobials, antifungals, anti-inflammatories, anesthetics and vasodilators. In fact, our Formulation Development team has already created and tested over 50 formulas that use Ellage and a broad range of APIs. PCCA members with Clinical Services support can access this growing list in our formula database .

4. Ellage can save your compounding pharmacy thousands of dollars in stability testing.

Stability-indicating testing methods that are required to extend beyond-use dates (BUDs) can cost tens of thousands of dollars for each formulation, depending on the type and number of APIs involved. But because it is anhydrous — with water activity below 0.6 (Aw <0.6) — Ellage allows pharmacy compounders to assign longer BUDs by default without having to send their formulations to analytical labs for stability testing. Aside from the convenience that these longer BUDs provide for patients (because they don’t have to refill their prescription as often), they also allow compounding pharmacies to increase their operational efficiency when making anticipatory batches of compounded medications.

Taken together, these characteristics and benefits make Ellage ideal in formulations for patients with a wide variety of vaginal conditions, which will help compounding pharmacies to meet their patients’ and prescribers’ needs. For more information about this unique compounding base, including specifications and links to more studies, visit our online product catalog .

These statements are provided for educational purposes only. They have not been evaluated by the Food and Drug Administration, and are not to be interpreted as a promise, guarantee or claim of therapeutic efficacy or safety. The references cited did not necessarily evaluate PCCA products or formulas included in these statements. The information contained herein is not intended to replace or substitute for conventional medical care, or encourage its abandonment.