Doxazosin Mesylate

Doxazosin mesylate is a quinazoline-based alpha1-adrenoceptor antagonist that relaxes smooth muscle in the prostate and bladder neck. Beyond its classical alpha-blocking activity, doxazosin modulates fibrosis-related gene expression in the rat ventral prostate. Following 7 and 30 days of doxazosin treatment at 25 mg/kg/day, ultrastructural analysis revealed thickened bundles of collagen fibrils and activated fibroblasts in the prostatic stroma. COL1A1 mRNA expression was significantly increased after 7 days, while COL3A1 expression was reduced after 30 days compared to controls. TGF-beta 1 mRNA and protein levels were elevated after 7 days of treatment, with mRNA levels remaining increased after 30 days. These findings demonstrate that relaxation of smooth muscle cells by alpha-blockade interferes with the mechanical dynamics of prostatic stroma extracellular matrix components, generating a pro-fibrotic effect likely via the TGF-beta 1 signaling pathway.

Fig. 1 Ultrastructure of the ventral prostate from control rats and from rats treated with Doxazosin. (Delella F K.; et al. 2012)

Doxazosin mesylate matrix patches were developed using solvent casting method with various ratios of HPMC K100 and PVP K30 polymers. The optimized formulation PF4 (HPMC K100:PVP K30 at 70:30 ratio with 2% DMSO) exhibited uniform thickness, good folding endurance of 128, drug content of 98.1 percent, and moisture content of 5.6 percent. In vitro drug release studies showed that PF4 achieved 94.3 percent release over 12 hours following first-order kinetics with a diffusion-controlled mechanism. FTIR studies confirmed no significant drug-polymer interactions.