Formulation and stability evaluation of ketoprofen sustained-release tablets prepared by fluid bed granulation with Carbopol 971P solution.

摘要

The objectives of the present study were: (1) to investigate the possibility of using a Carbopol polymeric solution as granulating agent by the fluid bed granulating process; (2) to select a suitable method of tabletting for sustaining the release of ketoprofen for 12 hr; (3) to perform stability studies according to International Committee on Harmonization (ICH) guidelines and photostability on ketoprofen SR tablets; (4) to study the influence of the storage conditions on release kinetics and melting endotherm of ketoprofen; and (5) to predict the shelf-life of the ketoprofen SR tablets. Tabletting ingredients were ketoprofen, anhydrous dicalcium phosphate, Carbopol 971P, talc, and magnesium stearate. Carbopol 971P solution (0.8% w/v) was used as a granulating solution in the fluid bed granulator. For comparative evaluation, tablets were also prepared by direct compression and wet granulation, and subjected to dissolution. Tablets prepared by fluid bed granulation technique were stored in incubators maintained at 37, 40, 50, and 60 degrees C, 40 degrees C/75% RH, 30 degrees C/60% RH, and 25 degrees C/60% RH, and in a light chamber with light intensity of 600 ft candle at 25 degrees C. Melting endotherms were obtained for the drug as well as the tablets during stability studies by differential scanning calorimetry. Tablets prepared by fluid bed granulation technique prolonged the release of ketoprofen better than tablets obtained by direct compression and wet granulation. Further, it complied with the requirements of ICH guidelines for stability testing. Higher temperature and humidity (40 +/- 2 degrees C/75% RH, 40 degrees C, 50 degrees C, and 60 degrees C) adversely affected the rate and extent of the dissolution. Ketoprofen SR tablets stored in amber-colored bottles demonstrated a good photostability for 6 months at 600 ft candle. The shelf-life of the formulation was predicted as 32 months.