Preparation and Evaluation of Freeze Dried Crystals of Ketoprofen using Lyophilization Monophase Solution Technique for Direct Compression Tablets

Ketoprofen, an anti-inflammatory drug, exhibits poor water solubility, dissolution and flow properties. Thus, the aim of the present study was to improve the solubility and dissolution rate of Ketoprofen by preparing crystals by freeze drying technique. Ketoprofen crystals were prepared by freeze drying using Isopropyl alcohol (IPA), chloroform and water as monophasic solvents system to enhance solubility and dissolution rate. The prepared crystals of Ketoprofen were evaluated for IPA and chloroform solvent residual by gas chromatography. The prepared formulations were characterized by scanning electron microscopy, differential scanning calorimeter; X-ray diffraction and Fourier transform infrared spectroscopy. Solubility and Dissolution profile of the freeze dried crystals was compared with its recrystallized sample and pure sample. The samples were stored in stability chamber to investigate their physical stability. Solvent residual of IPA and chloroform were found to be within the toxic level in prepared freeze dried crystals. Freeze dried crystals exhibited decreased crystallinity, the solubility of freeze dried crystals increasing nearly about fivefold than the ketoprofen pure sample. Dissolution of the ketoprofen crystals was significantly improved about three times higher than pure sample of ketoprofen. In stability test, the release profile of the freeze dried crystals was almost unchanged as compared with the freshly prepared freeze dried crystals stored at 40 ⁰C and 75% relative humidity for 90 days. The dissolution profiles of ketoprofen tablets prepared using freeze dried crystals exhibit greater dissolution behavior than tablets prepared by pure ketoprofen sample. Hence this technique can be used for formulation of tablets of ketoprofen by direct compression with directly compressible tablet excipients.