Reverse engineering and development of generic Orlistat formulation

Abstract

Orlistat a weight loss drug is off patented in US in 2009, it has the annual sales of around $100 million of the innovator’s product and has a high commercial potential in generic market. The marketed capsule formulation was decoded by differential solubility technique using methanol, methylene chloride and water as solvents and anti solvents. The quantity of API and excipients such as  Polyvinyl pyrrolidone, microcrystalline cellulose, Sodium lauryl sulphate, sodium starch glycollate and talc obtained after decoding is 118.60, 7.85, 84.95, 6.80 , 10.85 and 3.00 mg respectively. DSC thermogram of separated Orlistat gave a sharp endothermic peak at 46.5ºC.  PXRD values of the separated API obtained at 2θ are 11.2, 12.2, 14.0, 15.4, 16.9, 18.3, 19.2, 22.5, 25.0. Based on the quantities of the API and excipients obtained after decoding, generic form of the Orlistat capsule was prepared, which consists of pellets in capsules. The prepared generic form was characterized for weight variation of ± 3%, angle of repose 28.5˚ and drug content of 95.35%. Generic dosage form had similar dissolution profile with that of marketed products and showed first order drug release mechanism with R² of 0.9591. Greater similarity factor for dissolution was established with a value of 70.13.