Solid Dispersion of an HIV Protease Inhibitor

Abstract

LB71350 is an HIV protease inhibitor with poor aqueous solubility and extensive first pass effect. The purpose of the present study was to test the feasibility of solid dosage form of LB71350 with improved bioavailability utilizing solid dispersion. Three different compositions with varying ratio of (LB71350: Gelucire 44/14: Tween 20) were studied. Capsule filling of these solid dispersion compositions was tested using a semi-automatic capsule filling system. Oral bioavailability in dog was tested. Chemical and physical stability at 4, 25 and 40˚C was monitored by HPLC assay, dissolution test, powder XRD and microscopy. The capsule filling system yielded uniform products of drug loading up to 10%. Oral bioavailability in dog was improved compared to the aqueous suspension of crystalline LB71350. Capsules were chemically stable for up to 6 months at 40˚C. However, there were temperature and composition dependent physical changes. Decrease in dissolution rates after storage at 40˚C was due to the polymorphic change. In conclusion, manufacturing process, bioavailability, and physico-chemical stability have been considered to propose a solid dispersion capsule formulation for the HIV protease inhibitor with poor physico-chemical properties. A new less soluble crystalline form identified during the physical stability test warrants further study.