Influence of micro-environmental pH on the gel layer behavior and release of a basic drug from various hydrophilic matrices.
The purpose of this investigation is to understand the influence of gastrointestinal (GI) pH on the gel layer formation and its dynamics for various hydrophilic/swellable matrices, in the process of developing a pH-independent controlled release system for a basic drug, oxybutynin hydrochloride (OXB). Cylindrical matrices (8-mm diameter) without and with fumaric acid, were readily prepared by direct compression. Formulations were evaluated for in vitro drug release, and gel layer dynamics was studied by viscosity measurements and texture profiling analysis. In the in vitro drug release study, OXB, which shows pH-dependent solubility, showed faster release from all the matrices in pH 1.2 medium. Release rates enhanced to a lesser extent with change of medium from pH 6.8 to pH 1.2, for HPMC polymer matrices. Anionic polymer matrices showed drastic differences in the release rates when medium was changed from pH 6.8 to pH 1.2. Addition of fumaric acid to matrices demonstrated pH-independent drug release, which was attributed to the micro-environmental pH manipulation within the hydrated gel layer. Viscosity and texture profiling studies revealed that saturation solubility of drug at swelling front play a major role in the pH-dependent drug release from HPMC matrices, while both saturation solubility and the altered gel consistency as a function of pH are involved with anionic polymer matrices. Presence of fumaric acid in HPMC matrices showed efficient retardation and pH-independent drug release. In conclusion, understanding the influence of GI physiological pH on the gel layer dynamics and manipulating the micro-environmental pH provides efficient and predictable in vivo performance from these swellable cylindrical matrices.
Varma
Manthena V S
MV
National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, SAS Nagar, Punjab 160 062, India.
Kaushal
Aditya M
AM
Garg
Sanjay
S
D004337:Drug Carriers / Q000737:chemistry*; D005650:Fumarates / Q000737:chemistry; D005782:Gels; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008333:Mandelic Acids / Q000737:chemistry*; D008956:Models, Chemical; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D013608:Tablets, Enteric-Coated; D014783:Viscosity
D004337:Drug Carriers; D005650:Fumarates; D005782:Gels; D008333:Mandelic Acids; D011108:Polymers; D013608:Tablets, Enteric-Coated; C032005:fumaric acid; C005419:oxybutynin