Tablet Dosage Form Incorporating Glyburide Nanoparticles: Formula and Process Development

摘要

Sparingly water-soluble drugs such as Glyburideoffer challenges in developing a drug product withadequate bioavailability. The bioavailability of Glyburideis dissolution limited following oral administration. Theobjective of the present study was to develop a tabletdosage form for Glyburide incorporating drugnanoparticles to increase its saturation solubility anddissolution velocity for enhancing bioavailability whilereducing variability in systemic exposure. Glyburidenanoparticles were prepared using a wet bead millingtechnique. The solid-state properties of the drug beforeand after milling indicated no phase transitions based onX-ray powder diffraction (XRPD) and DSC analysis. Thenanosuspensions were converted into solid intermediateor granules by layering on to a water-soluble carrier suchas lactose. The granules showed particle size recoveryfollowing redispersion in water. The granules wereblended with excipients for tablet preparation. Thesaturation solubility of solid intermediate was assessed inphysiologically relevant medias and compared withunmicronized and micronized drug. The results indicatedthat saturation solubility (Css) of Glyburide significantlyimproved for nanoparticles as compared to unmilled andjet milled drug substance. The results from dissolutionstudies indicated that there was a significant increase inthe rate of drug dissolution for tablets incorporating drugnanoparticles as compared to a commercially availabletablet formulation. The process described herein forproduction of Glyburide nanoparticles using drug layeringtechnique is scalable and viable approach for commercialmanufacture of drug product with improved therapeuticoutcome.