title: Development of a doxazosin and finasteride transdermal system for combination therapy of benign prostatic hyperplasia.
abstract: The treatment of benign prostatic hyperplasia can be accomplished by the use of different drugs including, doxazosin, an α-1 adrenergic antagonist, and finasteride (FIN), a 5-α 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.
authors: Department of Pharmaceutics, Faculty of Pharmacy, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21.941-902, Brazil.
authors: Carolina Gonçalves
authors: CG
authors: Pupe
authors: Flávia Almada
authors: FA
authors: Do Carmo
authors: Valéria Pereira
authors: VP
authors: De Sousa
authors: Marlene
authors: M
authors: Lopes
authors: Bárbara
authors: B
authors: Abrahim-Vieira
authors: António José
authors: AJ
authors: Ribeiro
authors: Francisco
authors: F
authors: Veiga
authors: Carlos Rangel
authors: CR
authors: Rodrigues
authors: Cristina
authors: C
authors: Padula
authors: Patrizia
authors: P
authors: Santi
authors: Lucio Mendes
authors: LM
authors: Cabral
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000279:Administration, Cutaneous; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D001381:Azepines / Q000378:metabolism; D017292:Doxazosin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018120:Finasteride / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D007850:Lauric Acids / Q000378:metabolism; D008297:Male; D010539:Permeability; D014677:Pharmaceutical Vehicles / Q000378:metabolism*; D011470:Prostatic Hyperplasia / Q000188:drug therapy; D012869:Skin Absorption; D013552:Swine
chemical_list: D058891:5-alpha Reductase Inhibitors; D058668:Adrenergic alpha-1 Receptor Antagonists; D001381:Azepines; D007850:Lauric Acids; D014677:Pharmaceutical Vehicles; C030358:lauric acid; C035229:laurocapram; D018120:Finasteride; D017292:Doxazosin
keywords: combination therapy; doxazosin; epithelial delivery/permeability; finasteride; hydrogels; permeability; permeation enhancers; skin; transdermal drug delivery