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
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.