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

A wetting agent, properly known as a levigating agent, is a liquid used to displace the film of air that exists on the surface of dry powders. Every powder ingredient has a thin layer of air creating a barrier that may hinder the uniform mixing with the base (vehicle) used for a compounded formulation. The wetting agent removes this film of surface air by shear mechanical force and surrounds the powder. A wetting agent therefore facilitates mixing of insoluble powders in liquids and semisolids and may improve drug solubility. This helps facilitate uniform mixing to incorporate the ingredient into the base more evenly, avoid clumping and improve content uniformity of the final preparation.

When mixing a powder with a wetting agent in a mortar and pestle, levigation displaces surface air for insoluble and slightly soluble ingredients. When an ingredient is soluble, the surface air dissipates during dissolution.

The levigating step also reduces particle size due to the friction generated during mixing. Mixing processes such as using an electronic mortar and pestle (EMP) and syringe-to-syringe mixing may also accomplish this due to shear force, although the use of an ointment mill may be required to further reduce particle size.

Choosing the appropriate wetting agent depends on the specific formula, the vehicle involved and the route of administration. The agent selected should be miscible (compatible) with the vehicle used for the formulation. Some examples are discussed further below. The more viscous the wetting agent, the better its ability to displace surface air. Some of the other agents listed below may be preferred even though they have lower viscosity, particularly if the powder ingredient is soluble to slightly soluble.

It is generally recommended to use an amount of wetting agent that is equal to the amount of powder being levigated. However, this may not be possible for high powder concentrations, so most formulas will use up to a maximum of 10% wetting agent. The most common wetting agents used are Propylene Glycol USP (PCCA #30-1055) and Glycerin USP (PCCA #30-2865). Glycerin USP is the preferred wetting agent for vaginal preparations or other formulations where more moisturization is needed.

Also on The PCCA Blog: Choosing an Appropriate Gelling Agent for Your Compounded Preparation

Wetting Agents to Use with Aqueous Topical Vehicles

If the vehicle is aqueous, such as a cream or lotion, Propylene Glycol USP or Glycerin USP would be appropriate as the wetting agent since these liquids are miscible with water. However, as mentioned above, the specific formula and route of administration are also factors you must consider. If, for instance, you are compounding a vaginal preparation, then Glycerin USP would be best because it is one of the least irritating wetting agents and has moisturizing properties.

Other wetting agents used for aqueous topical vehicles include:

• Diethylene Glycol Monoethyl Ether NF (PCCA #30-3680)
• Dimethyl Sulfoxide USP (DMSO) (PCCA #30-1612)
• Purified Water USP
• Ethyl Alcohol, 190 Proof USP (PCCA #50-3161)

· Base C (Polyethylene Glycol 300 MW, NF Liquid) (PCCA #30-1012)

Wetting Agents to Use with Anhydrous Topical Vehicles

Similarly, if the vehicle is anhydrous, the wetting agent must be miscible with it, and you should also consider the specific formulation and the route of administration. For example, if using Petrolatum, White USP (PCCA #30-1024) as a base, the levigating agent of choice would be Mineral Oil, Light NF (PCCA #30-1291). When making a formula, sulfur topical ointment for example, it would replace the film of air on each sulfur particle with a film of mineral oil, which is compatible with petrolatum and would facilitate mixing.

Other wetting agents used for anhydrous topical vehicles include:

• Base G (Almond Oil NF (Sweet)) (PCCA #30-1027)
• Olive Oil NF (PCCA #30-3025)
• Diethylene Glycol Monoethyl Ether NF
• Propylene Glycol USP
• Glycerin USP
• Ethyl Alcohol, Anhydrous, 200 Proof, USP (PCCA #50-2999)

Examples of PCCA Bases and the Most Common Wetting Agents Used for Formulations

Note: There are some exceptions to the most common wetting agents or percentages used depending on the ingredient or combination of ingredients and the properties of the specific base used. PCCA members with Clinical Services support can contact our Clinical Services team with any questions or refer to our PCCA formula database to check for the specific formula they need.

Also on The PCCA Blog: Choosing the Appropriate Antimicrobial Preservative for Compounded Medication

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.

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.

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.

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.

References

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.