Effect of Different Crystallization Techniques on the Dissolution Behavior of Ketoprofen

Purpose: To enhance the solubility and dissolution characteristics of ketoprofen using various crystallization techniques.
Methods: Ketoprofen crystals were prepared by various crystallization technique including spherical agglomeration (SA), spray drying (SD), freeze drying (FD) and super cooling (SC). The crystallization medium used for all the techniques consisted of water and chloroform. Residual solvents in the crystals were determined and the crystals were characterized by DSC, FT-IR, XRD and SEM. Both solubility and dissolution behavior studies were carried out. The physical stability of the crystals were also evaluated after storage over a period of time.
Results: Residual IPA and chloroform in the crystals ranged from 4.10 - 5.70 and 1.84 - 2.57 ppm, respectively, which are well below their toxic limits. The crystals obtained exhibited lower crystallinity than the original drug. The solubility of FD crystals in water increased almost fivefold to 0.0926 mg/ml compared with that of the drug (0.0172 mg/ml), while the dissolution rates of the developed crystals were than that of the original crystals. For example, FD crystals demonstrated the highest dissolution (99.9 %) compared with original crystals (64.3 %). In the stability test, the dissolution profiles of the developed crystals remained largely unchanged over the period of the stability study.
Conclusion: The re-crystallization techniques used in this study can be applied to obtain modified ketoprofen for formulation of tablets of the drug with improved drug dissolution.