By Melissa Merrell Rhoads, PharmD, PCCA Director of Formulation Development; Courtaney Davis, BBA, PCCA Senior Formulation Specialist; Suki Pramar, PhD, PCCA Compounding Consultant; and Stacey Lemus, BS, PCCA Senior Formulation Specialist

There are several factors to consider when choosing an appropriate suppository base in pharmacy compounding. For example, is the intended therapeutic effect systemic or local? What is the route of administration — rectal, vaginal or urethral? Is the drug physically and chemically stable in the selected base? In addition to these questions, you must also consider patient comfort to ensure compliance.

Suppositories release drugs in the body either by melting at body temperature, or by dissolving in aqueous body fluids. The melting type of bases are fatty substances and include PCCA MBK^™ (Fatty Acid) and Cocoa Butter NF. The dissolving type contains polyethylene glycol (PEG) and includes PCCA Base A (Polyethylene Glycol 1450 MW, NF) or bases that are combinations of Polyethylene Glycol NF.

To help you decide which base is most appropriate for your suppository formulation, let’s explore some of the properties of various compounding bases as well as factors that you should consider in the selection process.

Suppositories for Systemic Administration

Pharmacists should discuss what is known and unknown about rectal absorption of the prescribed drug with the patient’s health care providers so that they can monitor the patients’ therapeutic results and adjust the medication when required. For systemic effect, we recommend using either PCCA Base A or PCCA MBK. Depending on the therapeutic use, the route of administration may be vaginal or rectal.

The drug release and systemic effect of PEG suppositories, including those made with Base A, vary depending on the amount of fluid present in the rectum or vagina (remember that PEG dissolves in body fluids). Under normal circumstances, there is enough fluid in the body cavity to completely dissolve the PEG base, allowing for complete release of the drug regardless of its affinity for the base. Therefore, you can use a PEG base to compound both hydrophilic and lipophilic drugs. PEG bases dissolve slowly over 30–40 minutes and get absorbed into systemic circulation with little to no drug leakage or loss.

For fatty, melting bases, such as Cocoa Butter NF, the drug must be able to partition out of the base for absorption to occur. For this reason, water-soluble, ionized forms of drugs are usually preferred in fatty bases. Typically, a lipophilic drug added to a fatty base may exhibit poor or erratic release from the base due to the strong physicochemical attraction between the drug and the base. However, PCCA MBK, which is a fatty base, contains a surfactant that helps with drug solubility and the release of lipophilic drugs. MBK suppositories melt quickly in the body cavity, within three to seven minutes, and therefore can result in some leakage and drug loss. Even though they may be used for systemic effect, fatty bases are generally used for local administration due to the rapid melting; the dissolving type of PEG bases may be used for local or systemic action due to the slower dissolution.

Suppositories for Local Administration

When suppositories are needed for a local effect, either PCCA MBK or Base A may be used for the vaginal or rectal route, while only Base A should be used for urethral administration since it retains its rigidity better upon insertion.

Physical and Chemical Stability

As always, you should review reference books, peer-reviewed literature and commercially available product information to provide information on factors that may affect the potency of the compounded formulation.

Patient Comfort & Ease of Use

PEG bases, including PCCA Base A, are hygroscopic, so they tend to absorb moisture from the surrounding tissue upon insertion. This may result in an unpleasant, stinging sensation at the site of administration. You must therefore counsel your patients to moisten the suppository with water prior to insertion. The moistening step lessens the hygroscopicity of the PEG base, making it less irritating. PEG suppository formulations do not require refrigeration (unless required for drug stability).

Fatty bases, such as PCCA MBK, tend to cause no irritation upon insertion. Suppositories made with them may soften at room temperature and are best stored in the refrigerator.

Tips for Compounding Suppositories

When compounding suppositories, be sure to check the melting point of your specific base. This may be found on the certificate of analysis. PCCA formulas will always list the melting range of the specific base in the formula procedure.

When filling suppositories, it is best to keep the preparation mixing in a beaker on a hotplate, while monitoring the temperature with a thermometer, and using a syringe to pull up the preparation and fill the molds. This will help ensure the best uniformity. PCCA members can find a free video on how to prepare suppositories using this method on PCCA Play.

Using PCCA Suppository Bases

PCCA MBK (Fatty Acid) (PCCA #30-1056)

• Melting fatty base
• Is a combination of hydrogenated vegetable oil and PEG-8-distearate (a surfactant)
• MucoLox^™ (PCCA #30-4782) may be added at 10% to help with mucoadhesion

Base A (Polyethylene Glycol 1450 MW, NF) (PCCA #30-1013)

• Dissolving PEG base

Base F (Witepsol H15^™) NF (PCCA #30-4840)

• Melting fatty base
• Composed of hydrogenated coco-glycerides
• When using Base F in a suppository, 5% Base G (Almond Oil NF (Sweet)) (PCCA #30-1027) is added to prevent cracking

PCCA Polypeg™ (PCCA #30-2883)

• Dissolving PEG base
• A blended polyethylene glycol suppository base with polysorbate 80. The polysorbate 80 helps to increase water solubility of poorly soluble drugs

Cocoa Butter NF (PCCA #30-1731)

• Melting fatty base
• If cocoa butter is heated too rapidly and/or cooled too quickly, it forms alpha crystals, which melt close to room temperature. Gentle, controlled warming followed by gradual cooling promotes formation of beta crystals, which melt closer to body temperature
• It is not recommended to use PCCA’s pink or blue molds with cocoa butter due to damage to the suppositories when trying to remove them from the molds

Using PCCA Suppository Molds

Suppository Shell Molds

• Available sizes: small, medium, large and extra large (refer to PCCA general formulas for mold capacities per base)
• Advantages: shells do not require lubrication, may be used as both mold and dispensing device, and are easy for patient to open
• Disadvantages: require backlight to view fill line when filling

Supposistrip Molds

• Available sizes: blue (smaller) and pink (larger) (refer to PCCA general formulas for mold capacities per base)
• Advantages: latex free, molds may be used as both mold and dispensing device
• Disadvantages: molds require lubrication, sometimes more challenging for patient to twist and remove suppositories

Rectal Rocket Mold (PCCA #35-2348)

• Uses a specific suppository mold to treat internal and external rectal conditions
• It is recommended to use bases or combinations that melt or dissolve much slower in order to maintain contact for a prolonged time
• Common bases used in the rectal rocket mold:

o PCCA MBK + paraffin wax

• Used in equal parts. If quicker-dissolving rectal rockets are requested, the ratio of the two bases may be changed from 50%/50% to 55%/45% (MBK/wax)
• MucoLox may be added at 10%

o Base A

• When using Base A in a rectal rocket suppository, 5% of PCCA Base C (Polyethylene Glycol 300 MW, NF Liquid) (PCCA #30-1012) should be added to prevent cracking

Lubricating Suppository Molds

Spray the rubber mold cavities with Mineral Oil, Light NF (PCCA #30-1291) or Medium Chain Triglycerides NF (30-4773) and allow excess to drain on a low-lint, disposable towel. The suppository shells do not require lubrication.

The rectal rocket suppository mold may be lubricated with Mineral Oil, Light NF; Medium Chain Triglycerides NF; or Polysorbate 80 NF (PCCA #30-1075) 2%/Glycerin USP (Natural) (PCCA #30-2865) (dissolve polysorbate 80 2% in glycerin) to help facilitate removal of suppository from the mold. Apply with clean, gloved fingers and rub to coat the mold thoroughly. Any of the lubricants listed can be applied or sprayed onto gloved fingers or directly to the mold. Then use gloved fingers to rub a uniform coating onto the mold.

PCCA members with Clinical Services support can see 35 general suppository formulas that use a variety of compounding bases in our formula database. PCCA’s general suppository formulas offer guidance on displacement, concentration of suspending agents and many other useful tips related to the base and preparation. Pharmacies with Clinical Services support also have access to the PCCA Suppository Calculator ^™ , which makes compounding suppositories easier by calculating ingredient quantities for you.

Melissa Merrell Rhoads, PharmD, PCCA Director of Formulation Development, received her pharmacy degree from Mercer University in Atlanta, Georgia, in 1995. She currently is involved with and oversees the development and implementation of new formulas at PCCA. She had more than six years of compounding experience with pharmacies in Georgia and Florida prior to joining the PCCA staff in 2004. Her areas of interest include women’s health, veterinary and pain management compounding.

Courtaney Davis, BBA, is a senior formulations specialist and technical consultant with more than 18 years’ combined experience in the pharmacy compounding industry. She joined PCCA’s Formulation Development department in 2005, where she assists in the creation of new formulas as well as continually updating and revising existing formulas. She works closely with the Quality Control team to ensure that PCCA’s chemicals and devices continue to perform to our highest standards in our formulas. In addition to this, Courtaney takes technical calls from our members regarding such topics as calculations, formula troubleshooting and equipment usage and works closely with our Research and Development team to bring technologically advanced and innovative products to our membership. Prior to joining PCCA’s staff, she worked for a member pharmacy as a certified technician.

Suki Pramar, PhD, is a compounding consultant at PCCA. She earned her PhD in pharmaceutics from the University of Houston in 1991, and she joined PCCA’s staff in 1999. Suki was appointed to the American Pharmacists Association’s Compounding Pharmacy Task Force in 2016.

Stacey Lemus, BS, became a compounding technician in 2000. She worked with a PCCA member pharmacy for more than 10 years before joining the PCCA Formulation Development team in 2012. Her work at PCCA focuses on new formula development as well as updating and testing existing formulations. Her experience with equipment, compounding techniques and calculations makes her a valuable resource for member technical calls. She received her BS in biology and chemistry from Texas A&M University – Kingsville.

References

Allen, L. V., Jr. (2007). Suppositories. Pharmaceutical Press.

Allen, L. V., Jr., & Ansel, H. C. (2014). Ansel’s pharmaceutical dosage forms and drug delivery systems (10th ed.). Lippincott Williams & Wilkins.

Kibbe, A. H. (Ed.). (2000). Handbook of pharmaceutical excipients (3rd ed.). Pharmaceutical Press.

Thompson, J. E., & Davidow, L. W. (2003). A practical guide to contemporary pharmacy practice (2nd ed.). Lippincott Williams & Wilkins.