Paper 2. Epigallocatechin Gallate and Tannic Acid Based Formulations of Finasteride for Dermal Administration and Chemoembolization.

Abstract

Finasteride is used to treat benign prostatic hyperplasia (BPH) and pattern hair loss (androgenetic alopecia or APA). The local administration of formulations with increased solubility and controlled release of finasteride are proposed using gallate-containing compositions within embolic microparticles or paste. Finasteride solubility in either epigallocatechin gallate (EGCG) or tannic acid (TA) solutions was assessed using HPLC. Poly(dl-lactide-co-glycolide) (PLGA) or poly(methylmethacrylate) (PMMA) microspheres (100-400μm) containing finasteride and EGCG or TA were effectively manufactured. Embolic particles were loaded with finasteride/EGCG/TA. Dermal uptake of TA/EGCG/finasteride topical compositions was measured in pig skin. The solubility of finasteride was dramatically increased using EGCG- or TA-based compositions. Finasteride loaded microspheres released over two months which was increased by EGCG or TA inclusion. Embolic particles soaked up finasteride and EGCG or TA and released the encapsulated drug over two weeks. Dermal uptake of finasteride from EGCG- or TA-based formulations was enhanced between 10 and 50 fold in layers as deep as 500μm when compared to a generic control formulation. Gallate-based formulations of finasteride increase drug solubility and allow for effective release of the drug from embolic formulations. Paste or powder EGCG- or TA-based formulations of finasteride greatly increase dermal penetration of the drug.