FORMULATION DEVELOPMENT AND PHARMACOKINETIC EVALUATION OF NANO TECHNOLOGY BASED ORAL DOSAGE FORM

摘要

Poorly water-soluble drugs such as Candesartan cilexetil and Camptothecin analog offer challenges in developing a drug product with adequate bioavailability. The bioavailability of these drugs is dissolution limited following oral administration. The objective of the study was to develop a tablet dosage form for these drugs incorporating drug nanoparticles to increase their saturation solubility and dissolution velocity for enhancing oral bioavailability while reducing variability in systemic exposure. Drug nanoparticles were prepared using a wet bead milling technique and converted into solid intermediate for tabletting using a spray granulation process. The solid-state transitions of nanoparticles were evaluated before and after milling using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). The granules were blended with excipients for tabletting and the dissolution characteristics of tablets evaluated in biorelevant media. There was no solid-state transition upon milling however; there was a significant enhancement in dissolution velocity for tablet dosage form incorporating drug nanoparticles as compared to the unmicronized and micronized drug. Systemic exposure studies in Wistar rats indicated a significant increase in the rate and extent of drug absorption