Development of a Doxazosin and Finasteride Transdermal System for Combination Therapy of Benign Prostatic Hyperplasia

作者：Pupe Carolina Goncalves; Do Carmo Flavia Almada^*; De Sousa Valeria Pereira; Lopes Marlene; Abrahim Vieira Barbara; Ribeiro Antonio Jose; Veiga Francisco; Rodrigues Carlos Rangel; Padula Cristina; Santi Patrizia; Cabral Lucio Mendes

来源：Journal of Pharmaceutical Sciences, 2013, 102(11): 4057-4064.

DOI：10.1002/jps.23715

• combination therapy
• doxazosin
• finasteride
• transdermal drug delivery
• epithelial delivery
• permeability
• hydrogels
• skin
• permeability
• permeation enhancers

The treatment of benign prostatic hyperplasia can be accomplished by the use of different drugs including, doxazosin, an -1 adrenergic antagonist, and finasteride (FIN), a 5- reductase inhibitor. Traditionally, treatments using these drugs have been administered as either a mono or combination therapy by the oral route. A transdermal delivery system optimized for doxazosin and FIN combination therapy would provide increased patient adherence and facilitate dose adjustment. Doxazosin base (DB) was prepared from doxazosin mesylate and characterized together with FIN, by X-ray powder diffraction (XRD), differential scanning calorimetry (DSC), and nuclear magnetic resonance (NMR). The permeation enhancers, azone and lauric acid, and the gelling agents, hydroxypropyl cellulose (HPC) and Poloxamer 407 (P407), were evaluated to determine their ability to promote in vitro permeation of drugs through the pig ear epidermis. Successful preparation of DB was confirmed by evaluating the XRD, DSC, and NMR patterns and in vitro studies revealed that 3% (w/w) azone was the best permeation enhancer. When P407 gel was compared with HPC gel, it showed reduced lag time and promoted higher permeation of both drugs. This may be because of the interactions of the former with the stratum corneum, which disorganizes the lipid structure and consequently promotes higher drug permeation.

• 出版日期2013-11