Paroxetine Hydrochloride Push-pull Osmotic Pump Tablets: Designing an Innovative, Scalable Push-pull Osmotic Drug Delivery System Using QbD Approach

摘要

Background: Paroxetine hydrochloride hemihydrate (PHH) is a serotonin reuptake inhibitoruseful for the treatment of diverse psychiatric problems. Existing marketed formulations with frequentadministration lead to gastrointestinal (GI) reactions and abrupt fluctuations in plasma level with poorpatient compliance. These prerequisites are sufficed by controlled release push-pull osmotic pump tablets(PPOP).Objective: Objective of the present study was to develop robust and reliable PPOP formulation viaQuality by design (QbD) approach to achieve desired release kinetics.Methods: PPOP was formulated using wet granulation method followed by osmotic coating. QbDstrategy for defining the risk assessment of influential variables such as swelling polymers andosmogen on in vitro release kinetics of designed PPOP.Results: Presence of Polyox in push and pull layer along with osmogen controlled the drug releasepattern from formulated PPOP system as depicted in 33 factorial design. These formulated optimizedPPOP systems demonstrated 2 hrs lag time with zero-order kinetics, a peculiar feature of PPOPs.Conclusion: Scalable, stable PPOP tablets were fabricated by applying systematic QbD approach. Thedeveloped PPOP systems with improved concentration-independent behavior helped to address thechallenges of existing marketed formulations. Risk mitigation and control strategy assured quality ofthe system during scalability. Application of QbD strategy in establishing the PPOP formulation wouldhelp in formulating drug candidates having gastric limitations and poor patient compliance. The presentstudy is the detailed account of QbD based PPOP formulation, therefore it can be of potential importancefrom academics as well as industrial perspective.