Development and optimization of osmotically controlled oral drug delivery systems for highly and poorly water soluble drugs

Abstract

In this research work, once daily push pull osmotic tablets of two highly soluble drugs (Ropinirole HCl and Ivabradine Hcl) and two poorly soluble drugs (Nisoldipine and Carvedilol phosphate) were developed, optimized and different factors affecting the release profile were extensively studied. The concept of QbD was applied and the design space was successfully obtained with the help of design expert software. Different statistical tools like ANOVA, regression analysis were used for the study. Analytical method was developed in pH 6.8 phosphate buffer for all the selected drugs. The drugs exhibited greater linearity at the selected ranges. Regression equations and R2 were created and studied for all the drugs in both the solvents. Pre formulation studies of the selected drugs like, organoleptic properties, solubility, flow property, particle size determination and drug excipients interaction study were performed and reported. The amount of the drug to incorporated in to the push pull osmotic tablets of the selected drugs were calculated with the help of the available labeled claim of the XR products and Robinson eriksen equation. Stability studies on the optimized push pull OT formulations of all the selected drugs were performed to assess their stability over time. The ICH guidelines were strictly followed during the stability study. None of the formulations showed any significant changes in any of the parameters evaluated. An In vivo animal study of the optimized formulations of all the selected drugs was performed to assess the in vivo performance of the dosage form. Pharmacokinetic parameters like tmax, Cmax, AUC0-t, AUC 0-and#8734;, Kel, t½ were determined and compared with the available marketed products of the selected drugs. So it can be concluded that in this research work, stable optimized formulations of push pull OTs of highly and poorly soluble drugs were successfully formulated and extensively studied the significant factors affecting the release pattern of the drug from the system with the help of design of experiments.