DEVELOPMENT OF EXTENDED-RELEASE FORMULATION BASED ON THE QUALITY BY DESIGN APPROACH

Important theoretical and practical task was solved - the scientific rationale for the methodological approaches to the development of extended-release tablets. For the first time, it was proposed the algorithm for pharmaceutical development of extended-release tablets uses a quality by design approach with nimesulide as a model active pharmaceutical ingredient. The target profile of the drug product was described and critical quality attributes were indicated. The risks of formulation variability were assessed. Taking into account the results of the development study, the risk of all variables was reduced to low. To obtain nimesulide extended-release tablets 27 excipients from 5 functional groups were studied, among which the release-controlling properties of 9 polymers were shown. The variance analysis method was used for statistical processing of experimental results, ranked series of advantages for 11 quality parameters were created. The preferred excipients were selected using the desirability function. The quantities of preferable excipients (7 quantitative factors) at 3 levels were identified by the random balance method. The optimal composition of nimesulide, prolonged-release tablets of 200 mg was established. In vitro drug release of nimesulide not less than 85% for an extended period of 24 hours was experimentally confirmed.