Characterization of a female controlled drug delivery system for microbicides.
In this study, the feasibility of a carbopol 934P-HPMC-based gel formulation as a vaginal drug delivery system was evaluated. A vaginal fluid simulant (VFS) was utilized to simulate human vaginal mucus. The viscosity of the carbopol-HPMC gel system and VFS was examined using a cone and plate viscometer. The surface tension of VFS was measured using a capillary rising method. Differential scanning calorimetry (DSC) was employed to investigate the effect of carbopol gel on the conformational changes of rat vaginal membrane. The viscosity of carbopol gel increased as the pH of the system increased from 4.0 to 6.0. The viscosity of HPMC gel remained the same irrespective of pH of the system. The viscosity of the carbopol gel significantly increased, when HPMC (0.5-1.5%) was added to the system. The optimal viscosity value (1.5-2.0 poises) was achieved at 1.0-1.5% carbopol (pH 4.0) with the presence of 1.0-1.5% HPMC. There were mucin concentration dependent changes in viscosity and surface tension of VFS. The results of DSC analysis of rat vaginal membrane showed that the profiles of thermal stability for both carbopol-treated and the untreated control at the temperature ranging from 40 to 90 degrees C were almost identical. The thermal denaturation temperatures (Td) of the carbopol-treated membrane and the untreated control were not significantly different from each other. The combination of carbopol and HPMC seems to be an ideal formulation as a vaginal delivery system. Mucin played an important role in the regulation of viscosity and surface tension of VFS. DSC study demonstrated that carbopol gel showed good biocompatibility and did not cause any conformational changes in rat vaginal membrane.
Wang
Yicheng
Y
Department of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 64110, USA.
Lee
Chi H
CH
D000179:Acrylates; D000282:Administration, Intravaginal; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage*; D001672:Biocompatible Materials; D002582:Cervix Mucus / Q000502:physiology; D016503:Drug Delivery Systems; D005260:Female; D005782:Gels; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007785:Lactose / Q000031:analogs & derivatives*; D008747:Methylcellulose / Q000031:analogs & derivatives*; D009077:Mucins / Q000494:pharmacology; D010078:Oxazines; D051381:Rats; D012996:Solutions; D013500:Surface Tension; D014783:Viscosity
D000179:Acrylates; D000890:Anti-Infective Agents; D001672:Biocompatible Materials; D005782:Gels; D009077:Mucins; D010078:Oxazines; D012996:Solutions; D008747:Methylcellulose; C071191:MK 458; D007785:Lactose; C453622:carbopol 934P