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

Background: Paroxetine hydrochloride hemihydrate (PHH) is a serotonin reuptake inhibitor useful for the treatment of diverse psychiatric problems. Existing marketed formulations with frequent administration lead to gastrointestinal (GI) reactions and abrupt fluctuations in plasma level with poor patient 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 via Quality by design (QbD) approach to achieve desired release kinetics. Methods: PPOP was formulated using wet granulation method followed by osmotic coating. QbD strategy for defining the risk assessment of influential variables such as swelling polymers and osmogen on in vitro release kinetics of designed PPOP. Results: Presence of Polyox in push and pull layer along with osmogen controlled the drug release pattern from formulated PPOP system as depicted in 33 factorial design. These formulated optimized PPOP 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. The developed PPOP systems with improved concentration-independent behavior helped to address the challenges of existing marketed formulations. Risk mitigation and control strategy assured quality of the system during scalability. Application of QbD strategy in establishing the PPOP formulation would help in formulating drug candidates having gastric limitations and poor patient compliance. The present study is the detailed account of QbD based PPOP formulation, therefore it can be of potential importance from academics as well as industrial perspective.