Formulation of a Fast-Dissolving Ketoprofen Tablet Using Freeze-Drying in Blisters Technique

Abstract

ABSTRACTThe aim of this work was to develop a ketoprofen tablet which dissolve-rapidly in the mouth, therefore, needing not be swallowed. The solubility and dissolution rate of poorly water-soluble ketoprofen was improved by preparing a lyophilized tablet (LT) of ketoprofen using freeze-drying technique. The LT was prepared by dispersing the drug in an aqueous solution of highly water-soluble carrier materials consisting of gelatin, glycine, and sorbitol. The mixture was dosed into the pockets of blister packs and then was subjected to freezing and lyophilization. The saturation solubility and dissolution characteristics of ketoprofen from the LT were investigated and compared to the plain drug and the physical mixture (PM). Results obtained showed that the increase in solubility of ketoprofen from LT matrix, nearly three times greater than the solubility of the plain drug, was due to supersaturation generated by amorphous form of the drug. Results obtained from dissolution studies showed that LT of ketoprofen significantly improved the dissolution rate of the drug compared with the PM and the plain drug. More than 95% of ketoprofen in LT dissolved within 5 min compared to only 45% of ketoprofen plain drug dissolved during 60 min. Initial dissolution rate of ketoprofen in LT was almost tenfold higher than that of ketoprofen powder alone. Crystalline state evaluation of ketoprofen in LT was conducted through differential scanning calorimetry (DCS) and x-ray powder diffraction (XRPD) to denote eventual transformation to amorphous state during the process. Scanning electron microscopic (SEM) analysis was performed and results suggest reduction in ketoprofen particle size.