Novel highly-swellable and pH-responsive slow release formulations of clotrimazole with chitosan-g-PEG/starch microparticles

Abstract

Slow drug release from swellable matrices has attracted attention among researchers due to its target-specificity and the economics of slow release strategy. For this purpose, we synthesized chitosan (CS) and modified same by grafting with polyethylene glycol (PEG). The CS-g-PEG was blended with starch (ST), crosslinked with sodium tripolyphosphate (TPP) and loaded with clotrimazole (CTZ) as a model drug. These microparticles (beads) were characterized by FTIR, TGA, and SEM. The swelling rates of the beads in acidic and basic media which decreased as pH increased were better described by second-order kinetics. The amounts of CTZ released from the beads increased as the ST composition increased but generally decreased for the TPP-crosslinked beads. Cumulative CTZ release of 61.72 and 34.31% were obtained for the uncrosslinked and TPP-crosslinked 0.5:0.5 CS-g-PEG:ST beads in 60 min, respectively. Their release rates were best described by zero-order kinetics while the release mechanism followed less-Fickian diffusional release, with release exponents ranging from 0.08 to 0.39. Hitherto, there is no literature on the release of CTZ from uncrosslinked and/or TPP-crosslinked CS-g-PEG:ST beads. Our findings show that these novel CS-g-PEG:ST beads can be utilized for the in vitro slow release of CTZ, with potential for in vivo application.