Development and in vivo evaluation of novel monolithic controlled release compositions of galantamine hydrobromide as...

The objective of this study is to develop and in vivo evaluation of novel monolithic matrix mini tablets approach to control the release of galantamine hydrobromide (GAH) in comparison with desired release profile to the Innovator formulation Razadyne(®) ER capsules. The direct compression method was employed for preparation of matrix mini tablets as against reservoir multiparticulate pellets of innovator formulation. The matrix swellings, dissolution similarity, mean dissolution time and dissolution efficiency of formulations were evaluated. It was found that increase in the concentration of high viscosity hydroxypropylcellulose (HPC) results reduction in release rate. The drug release was shown to be pH dependent with faster rate at lower pH. The release of GAH followed first order shifting to dissolution dependent by increase of HPC content. The formulation showed stability of drug release. In vivo prediction was done by Wagner-Nelson method. Prediction errors were estimated for Cmax and area under curve (AUC) and found to be not exceeding 15%. In vivo study in human volunteers confirmed the similarity between test and innovator formulations and pharmacokinetic values were comparable between actual and predicted. These results suggest that novel monolithic matrix approach could be suitable technique to formulate controlled release GAH.