Evaluation of the In Vitro Percutaneous Absorption and Stability of Progesterone Topical Compounded Medications

Progesterone plays an important role in early pregnancy by thickening the uterine lining and creating an appropriate environment for implantation of the fertilized egg. Progesterone supplementation is commonly prescribed to women as part of infertility treatments. The exogenous hormone may be delivered through various routes of administration, most commonly oral, topical/transdermal, vaginal and intramuscular. Transdermal compounded medications, using permeation-enhancing topical bases, represent a promising dosage form which is non-invasive, easy to administer and customizable to meet the individual patient’s needs. In this in vitro study, progesterone USP (special micronized) was incorporated in a proprietary anhydrous permeationenhancing gel base (APEB), and also in a proprietary water-containing cream base (VBC) for comparison purposes. The skin percutaneous absorption of the hormone was evaluated using the Franz skin finite dose model and mass spectrometry. Additionally, the stability of the hormone was determined using a validated, stability-indicating Ultra-Performance Liquid Chromatographic (UPLC) method. Progesterone in APEB showed an average optical density of 1699 compared with progesterone in VBC which had an average optical density of 550. Statistical analysis shows a significant difference (p<0.029) in the skin permeation of progesterone compounded in APEB or VBC. These results suggest that anhydrous APEB is potentially a better base to compound progesterone compared with water containing VBC. The better efficacy of APEB may be attributed to its chemical composition. APEB contains phosphatidylcholine and jojoba esters, which may have contributed to its permeation-enhancing property. The anhydrous property of APEB also provides for better solubility of the nonpolar progesterone and unfavorable conditions for growth of microorganisms, without compromising the efficacy of the skin permeation. The stability of progesterone in APEB was tested at room temperature for 180 days and it was concluded that the concentration of progesterone ranged between 96% – 106% relative to its initial concentration, as shown in Figure 2. As such, progesterone in APEB has an extended beyond-use-date of 6 months, which reinforces the benefits and convenience of using this anhydrous formulation. Results from this pre-clinical in vitro evaluation can be used as basis for a warranted clinical trial in using APEB as a base for compounded topical progesterone in hormone replacement therapy.

Disclosure: The authors are employees of PCCA, the manufacturer of the proprietary compounding bases APEB and VBC discussed in this study.