Formulation and Physical characterization of microcrystals for dissolution rate enhancement of Tolbutamide

Abstract

Tolbutamide (TBM) is a first-generation sulphonylurea, used for treatment of non-insulin dependent diabetes mellitus. Tolbutamide is practically insoluble in water and its dissolution is the rate-limiting step for its absorption, which leads variable bioavailability. The aim of this investigation was to enhance the dissolution rate of Tolbutamide by formation of microcrystals using solvent change method. The in situ micronization process was carried out using solvent change method in the presence of Polyvinylpyrrolidone (PVP) as stabilizing agents that limits the size of the particles generated. TBM was dissolved in methanol and the stabilizing agent in water (as non-solvent). The non-solvent was poured rapidly into the drug solution under stirring by a magnetic stirrer, and the resultant was oven-dried. Microcrystals were characterized by optical microscopy, SEM, FTIR, DSC, XRD and in vitro powder dissolution study. TBM microcrystals showed narrow particle size and change in crystalline shape from rod-shape to. FTIR and DSC results showed no interaction between the drug and the stabilizer. XRD diffractograms of microcrystals showed smaller peak height than untreated TBM indicates that crystal habit modification occurred in the microcrystals without any polymorphic changes. Negative Gibb’s free energy change represented spontaneous solubility of microcrystals. Dissolution efficiency of TBM microcrystals at 15 min. (DE_15%) was increased about 9 times. Microcrystals were found to have good flow property.