Two Sustained Release Membranes Used in Formulating Low Strength Testosterone Reservoir Transdermal Patches

Abstract

Introduction: Several Testosterone Replacement Therapies exist for hypogonadism, but an in-depth analysis of these products reveals a high dosing frequency and a high drug loading, up to 120 mg for a potent drug like Testosterone. This may lead to patient non-compliance and toxicity problems if used improperly. Androderm^® is the only 24-hour marketed transdermal patch. Testopel pellets are another extended-release product given subcutaneously every 3-6 months. But it requires surgical implantation and is associated with severe adverse effects. For this reason, the development of other extended- release testosterone products is needed. The study aims at using different excipients for the exploration of sustained-release patches.

Methods: Reservoir formulations were prepared using Carbomer 941 and HPMC K100M as the sustained- release polymers plus CoTran™ 9702 and CoTran™ 9712 as the release membranes. The formulated patches were subjected to in vitro dissolution for 24 h. The amount of drug release at each time point was determined using the developed HPLC assay. FDA Similarity Factor, f₂, t-test, and ANOVA were applied to all nine-point collected samples.

Results: CoTran™ 9712 membrane was found to be a better candidate than CoTran™ 9702. The in vitro release profiles of the four formulations were compared (Carbomer vs. HPMC, and CoTran™ 9702 vs. CoTran™ 9712).

Conclusion: CoTran™ 9702 releases testosterone significantly lower. Carbomer and CoTran™ 9712 were the best formulation among all with the highest drug release of 2.16 ± 0.36 mg.

Keywords: CoTran™ membrane film; FDA Similarity Factor f_{2 values; HPLC stability indication study; In vitro paddle over disc dissolution; Testosterone; ethylene vinyl acetate; reservoir transdermal patch..}