An Investigation into the Suitability of Amidated Pectin Hydrogel Beads as a Delivery Matrix for Chloroquine

Abstract

The aim of the present study was to delay the release of chloroquine to distal parts of the gastrointestinal tract by using a multiparticulate hydrogel formulation. Amidated pectin chloroquine beads (PC) with varying pectin-to-chloroquine ratios (PC) w/w loadings of 4:1, 2:1, and 1:1 in the dried beads were prepared by the gelation of drug-loaded pectin solutions in the presence of calcium. In vitro release studies of chloroquine from pectin-chloroquine hydrogel beads and chloroquine diphosphate powder were carried out in simulated gastric and intestinal fluids. The total release of the entrapped chloroquine from the hydrogel beads was achieved between 4 and 7 h in simulated intestinal fluid, but total release was not achieved in simulated gastric fluid. However, total release from chloroquine diphosphate powder was achieved by 1.5 and 2 h in gastric and intestinal fluids, respectively. The plasma pharmacokinetics of chloroquine from pectin hydrogel beads and chloroquine diphosphate solution following single or repeated dosing were compared in male Sprague-Dawley rats over a period of 60 h. Oral administration of the hyrogel beads to rats produced maximum plasma concentrations by 7 h, but highest plasma concentrations following chloroquine solution administration were observed by 2 h. The dissolution data and appearance of significant plasma concentrations of chloroquine 2 to 4 h after oral administration suggests release in duodenum, jejunum, or ileum.