Inclusion Complexation of Anti-HIV Drug with β-Cyclodextrin

Abstract

The purpose of present investigation was to investigate the effect of complexation of Nelfinavir Mesylate (NM) – an Anti-HIV drug with Beta-cyclodextrin (β-CD) on its dissolution characteristics and subsequent effect on its absorption properties and bioavailability. Phase solubility studies were conducted to find the interaction of NM with β-CD. Physical mixing and milling method were used for complexation. The inclusion complexes were characterized by X-ray diffractometry, FT-IR and NMR studies and further studied by in-vitro dissolution testing. The plain NM and complex was subjected to intestinal absorption studies by using Everted intestinal sac model. Data was treated statistically by Mann–Whitney U test. Pharmacokinetic studies were carried out in rabbits using cross over design and data was treated by Student’s t test. Phase solubility studies confirmed 1:1 complex formation of NM with β-CD with stability constant of 204.84 M−1. In-vitro dissolution studies of inclusion complexes of NM with β-CD prepared by milling method (T90=60.89 min) showed better dissolution rate kinetics in distilled water in comparison with plain NM (T90=374.31). The increased solubility with decreased crystallinity is attributed by inclusion of NM in the cavity of β-CD, which was further confirmed by instrumental studies. Intestinal absorption studies further supports these findings by showing 2.13 times enhancement in the absorption rate of complex as compared to plain NM. The percent relative bioavailability of complex in rabbits was 185.37 as compared to the plain NM.