STABLE COMPOSITION AND SIMPLE MANUFACTURING PROCESS OF PREGABALIN CAPSULES

Abstract

Pregabalin is indicated for epilepsy. Pregabalin drug product is available in market as Solution, Capsules and Extended Release tablets. This research aims to formulate a stable composition and process for Pregabalin Capsules that exhibits comparable physico-chemical characteristics to brand product capsules. Before initiating the formulation work, API and Brand product was completely characterized. Excipients were selected based on the brand product characterization and Drug-Excipient compatibility study. Based on the API characterization, brand product characterization and Drug-Excipient compatibility study, preliminary formulation work was initiated. A direct blending process was followed for final blend preparation. The final blend was filled into capsule shells using ACG-Pam MF-30 capsule filling machine. During stability evaluation of different prototypes at accelerated storage condition of 40°C / 75% RH, the formulation containing Colloidal Silicon Dioxide showed higher level of impurity, Pregabalin Related Compound-C (4-Isobutylpyrrolidin-2-one) or Pregabalin Lactam Impurity. The observation of incompatibility of Pregabalin with Colloidal Silicon Dioxide was doubly confirmed by Drug-Excipient compatibility studies. When the incompatibility reaction was investigated at molecular level, it was observed that one mole of water gets released when Pregabalin reacts with Colloidal Silicon Dioxide. This was further confirmed by mass balancing the molecular weights of reactants, Pregabalin and Colloidal Silicon Dioxide with the product, Pregabalin Related Compound-C. Thus the final formulation was made without Colloidal Silicon Dioxide and has Lactose Anhydrous as diluent; Pregelatinized Starch as Binder and Disintegrant; and Talc as glidant and lubricant. The drug product showed comparable physico-chemical characteristics with brand and also found to be stable.