Modulating Gliclazide Release and Bioavailability Utilizing Multiparticulate Drug Delivery Systems

Abstract

To formulate multiparticulate controlled-release alginate-gelatin (AL-GL) beads in order to modify gliclazide (GLZ) release rate. AL-GL beads were prepared using different glutaraldehyde concentrations and dried using either air or freeze-drying method. For comparison, calcium alginate beads (AL-beads) were prepared at different temperatures. Drug incorporation efficiency, beads swelling%, drug release rate, and kinetics in gradient conditions (USP Apparatus-4) were studied. Selected AL-GL beads, as a test formulation (T), were in-vivo compared with Diamicron® 80 mg conventional tablet (R). AL-beads curing temperature was inversely proportional to GLZ incorporation efficiency and directly proportional to beads swelling%. GLZ release from AL-beads was slow in 0.1 N HCl and very fast in pH 7.4. In case of AL-GL beads, GLZ incorporation efficiency and swelling% were inversely proportional to glutaraldehyde concentration. AL-GL beads showed zero-order release of GLZ for up to 11 h. Scanning electron microscope (SEM) images of the freeze-dried beads showed a highly porous surface. Differential scanning calorimetry (DSC) and Fourier transform infra-red (FT-IR) studies indicated an interaction between alginate and gelatin due to crosslinking, while FT-IR indicated the absence of chemical interaction with GLZ. The relative bioavailability (T/R) was 97.57, 138.34, and 143.53%, for Cmax, AUC0–72, and AUC0–∞, respectively. Tmax of T was significantly higher than R. AL-GL beads could represent promising delivery systems for modulating GLZ release rate and minimizing the variation in its absorption.