Optimization of a formulation of ketorolac tromethamine using DoE

Abstract

The oral sustained release drug delivery system is often considered as one of the most convenient forms of drug administration over conventional dosage forms due to its ability to maintain an effective therapeutic efficacy and contribution to rational drug therapy. As the sustained release dosage form allows slow release of the drug and maintains the constant therapeutic blood or tissue drug level for an extended period of time, it is one of the most widely used drug delivery systems. The main purpose of using the sustained release dosage form is to decrease frequency of drug intake, thus reducing adverse effects associated with the drug and also to ensure better patient compliance. The aim of the present study was to formulate an optimum formulation of the sustained release oral tablet dosage form of Ketorolac Tromethamine. Since Ketorolac Tromethamine has a short biological half-life, it can be considered to formulate as a sustained release dosage form in order to reduce the dosing regimen and subside the gastrointestinal adverse effects that is likely to occur from its frequent consumption. For the purpose of formulation design, nine formulations have been designed for 200 mg and 250 mg matrix tablets each. The different polymer ratio employed to formulate the tablet shows the impact on drug release from the dosage form. The excipients for the formulations have been selected based on the FT-IR and DSC study that justifies the compatibility of excipients with the API. The dissolution study has been done for all designed formulations in order to get the drug release profile at different time interval and these release profiles have been placed into different mathematical release kinetic models in order to get the best fitted model for release rate. Finally, the optimum formulation for the two different doses was determined using Design Expert Software which was F5 for 200 mg of Ketorolac Tromethamine matrix tablets.