Development and Optimization of Controlled Drug Release Formulation of Diclofenac Sodium Based on Osmotic Technology.

The aim of this study is to develop and optimize an osmotically controlled drug delivery system of Diclofenac sodium. Osmotically controlled oral drug delivery systems utilize osmotic pressure for controlled delivery of active drugs. Drug delivery from these systems, to a large extent, is independent of the physiological factors of the gastrointestinal tract. Differential scanning calorimeter (DSC) was used to evaluate the drug-excipient compatibility, based on the results of DSC, excipients defined in the formula were found to be compatible with Diclofenac sodium. Formulation variables like type of osmotic agent (Sodium chloride, Mannitol, Lactose), level of pore former and plasticizer, percent weight gain were found to affect the drug release from the developed formulations. The release performance of Diclofenac sodium from the optimized formulations was studied over a period of 12 h. Drug release was inversely proportional to the membrane weight but directly related to the initial level of pore former in the membrane. On the basis of release results, a three-level three-factorial Box-Behnken experimental design was used to characterize and optimize three formulation parameters, i.e. level of osmotic agent, pore former and plasticizer. The chosen dependent variables (responses) were a cumulative percentage of dissolved diclofenac sodium over a period of 12 h.. The release from the developed formulations was independent of pH and agitationalintensity, but dependent on the osmotic pressure of the release media. From dissolution models it was observed that drug release from optimized formulation exhibited zero order release kinetics. The formulations were found to be stable after 3 months of accelerated stability studies (40 degrees C and 75% RH). Prediction of steady-state levels using the superposition method showed the plasma concentrations of Diclofenac sodium to be within the desired range.