ABSTRACT

Flutamide, an anticancer drug for prostatic carcinoma has poor aqueous solubility and low oral bioavailability. The study aims to enhance the aqueous solubility and dissolution of flutamide by developing a Flutamide freeze dried tablet (FDT). The FDT was prepared by dispersing the drug in an aqueous solution of highly water-soluble carrier materials consisting of gelatin, lysine, and sorbitol. The mixture is poured in to the pockets of blister packs and subjected to freezing and lyophilization. The drug in FDT is characterized by DSC, XRD and SEM and evaluated for saturation solubility at pH 1.2 and 7:2 .Dissolution studies are carried out and compared with physical mixture (PM) and pure drug. The samples are stored in stability chamber to investigate their physical stability. The DSC and X-ray study implies that crystalline state of Flutamide in FDT is transformed to amorphous state during the formation of FDT. The SEM result suggests reduction in flutamide particle size in FDT (1-4um) than pure flutamide (19-37 um). The solubility of Flutamide from the FDT was nine and half times higher (0.0883 mg/mL) than the pure drug (0.0095 mg/mL) in water. The solubility of flutamide from FDT in both pH 1.2 and 7.has increased to twelve and thirteen times higher than the pure drug. The dissolution studies showed that dissolution of drug from FDT (97.76% at 20 min) was significantly improved compared with the pure drug (29.21% at 60 min). The stability test suggests that, the release profile and drug content of the FDT is almost unchanged as compared with the freshly prepared FDT after 90 days storing. Based on these results, it can be concluded that Flutamide can be formulated in to freeze dried tablets with enhanced solubility and dissolution in water.