Implementation of Quality by design in formulation and development

Abstract

Quality by Design (QbD) concept for formulation development has been recently newlineimplemented by USFDA and it is being brought into practice worldwide gradually. newlineThe elements of QbD are still not very well understood and are going through scrutiny newlineby all major researchers, research institutes and industry. However, there is no dispute newlineon the fact that the QbD approach, if planned judiciously and followed appropriately newlineshall result in a robust product. In the current work, we have attempted to use the newlinebasic principles of QbD for the development of new formulations. newlineWe decided to develop various novel formulations of Clopidogrel bisulfate (CLB). newlineCLB is a potent antiplatelet agent that reduces the risk for thrombotic events in newlinepatients with atherothrombotic diseases. The anti-thrombotic activity of this drug newlinemakes it a potential candidate for being developed as a delayed release formulation. newlineSo that effective plasma concentrations of the drug can be achieved and maintained at newlineall times, including the early morning hours, when there are highest chances of heart newlineattack. Following is the summary of the current work newline8.1.1. Pre-formulation Studies newlinePre-formulation studies were carried out for CLB as well as all potential excipients, to newlineget an idea about their physical and chemical properties. Various analytical techniques newlinewere used for characterization and they included DSC, FTIR, HPLC and so on. CLB newlineexhibited good flow properties and good solubility in 0.1 N HCl, so this medium was newlinechosen for dissolution studies. All potential excipients were checked for their newlinecompatibility with CLB and it was found compatible. The risk assessment was carried newlineout to assess impact of CLB and excipients over formulation development.The pre-formulation studies revealed that CLB is stable in acidic pH, poorly soluble newlinein alkaline pH and has a narrow absorption window. Based on these findings, it was newlinespeculated that, CLB could be designed to remain in the stomach for more time and newlinethus be formulated into gastroretentive systems. newline newline