ABSTRACT:
Proposed research work was carried out with an objective to utilize chitosan as a release controlling polymer in developing a once daily formulation of a freely water soluble drug Venlafaxine hydrochloride (VNH) and demonstrate its potential in oral controlled release systems. Triple layered tablets containing VNH equivalent to 150 mg of Venlafaxine were prepared in which middle drug layer containing Hydrogenated vegetable oil (HVO), in order to conceal maximum surface area available for drug release was covered from upper and lower side with polymeric barrier layers consisting of hydrophilic and lipophilic excipients, which together with chitosan gave flexibility as well as strength to the formulation. Limited available surface area from the middle layer produced controlled diffusion of drug as the rigid lipid core virtually submerged in the swollen backing layers producing a pH independent dissolution rate. Formulation was optimized with 3 level factorial designs to obtain a desired 20 hrs release profile in distilled water. Amounts of chitosan (X1) and hydrogenated vegetable oil (X2) were selected as independent variables and times required for 20% (T20), 50% (T50) and 90% (T90) drug release were selected as dependent variables. A mathematical model was generated for each response parameter and release profile of optimized composition was fitted for different controlled release models concluding that the lipophilic middle layer and hydrophilic chitosan layers were required to obtain desired drug release pattern fitting to peppas model and the formulation also shown stability on storage at room temperature and accelerated conditions of temperature and humidity.