Optimized ciprofloxacin release from citric acid crosslinked starch-PVA hydrogel film: modelling with mixture design

Abstract

Projecting optimal composition for hydrogel blends, while designing sustained release formulation of hydrophilic drug, is of paramount importance. In present study, composite hydrogel incorporating ciprofloxacin (0.2% w/w) was prepared by sequential addition of polyvinyl alcohol (PVA) (20–95% w/w), starch (0–75% w/w), citric acid (5–80% w/w) as cross-linker in a heat-induced gelatinization process. A constrained simplex mixture design was adopted to rationalize the proportion of ingredients in hydrogel composition while modelling the time required for 50% drug release from the hydrogel under in-vitro conditions. Prepared hydrogels were also characterized for swelling ratio, tensile strength, and antimicrobial disc-diffusion assay. Decreasing proportion of starch relative to PVA results in a transparent hydrogel, with a high degree of equilibrium swelling (up to 104%). Drug release from all hydrogel blend arguably followed Korsmeyer-Peppas release kinetics with quasi-Fickian to non-Fickian release behaviour. The time required for 50% drug release and the hydrogel dissolution was proportional, indicating disintegration-controlled release rate. Reduced cubic-model based on the forward selection offered good agreement with experimental data (R2, 0.98 and adjusted R2 of 0.91). Optimal blend projection by the model with a mass ratio of 0.38:0.21:0.41 for PVA: Starch: citric acid was verified to be reasonably correct.