DEVELOPMENT OF NOVEL INJECTABLE FORMULATION OF CLOPIDOGREL BY QbD APPROACH

Clopidogrel, a poorly water-soluble drug, has been the mainstay of platelet management in acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) for over a decade. Since Clopidogrel is a prodrug and requires hepatic metabolism for activation, it exhibits a slower onset of action upon oral administration. This time-lag before the onset on the action is highly undesirable for the treatment of critical conditions such as coronary intervention, which is a medical emergency during which the rapid onset of antiplatelet action is of paramount importance. To achieve rapid onset, intravenous is the preferred route of administration; however, due to poor aqueous solubility, development of the IV formulation of Clopidogrel presents a considerable challenge. In the present investigation, the liposomal formulation of Clopidogrel was developed, which enables IV administration and may potentially provide a rapid onset of action. The formulation was prepared and optimized using 3² full factorial designs with Design Expert 11 software and evaluated for critical quality attributes (% entrapment, particle size, PDI, zeta potential and Morphology, pH/dilution induced stability and short term stability studies. The particle size of optimized formulation was 94.5 ± 2.8 nm, with PDI of 0.126 ± 0.012 and entrapment efficiency (EE) of 89.2 ± 2.1. The developed formulation was stable over a study period of 3 months at 2°-8 °C. This formulation has great potential as rapid-acting IV formulation to fulfill the unmet need in the management of cardiovascular emergency like (ACS) and PCI.