β-Cyclodextrin mediated controlled release of phenothiazine from pH-responsive pectin and pullulan-based hydrogel optimized through experimental design

Abstract

Drugs with lower permeability and water solubility provide major challenges for producing safe and efficient formulations. The current work aims to prepare ICs of the drug phenothiazine and β-cyclodextrin via physical, microwave, freeze-drying, and kneading methods. Many analytical methods, such as ¹H NMR, ROESY, FT-IR, DSC, SEM, and XRD, were then used to confirm the formation of inclusion complexes. The natural polysaccharide-based hydrogel comprising pectin and pullulan was synthesized in air and optimized through various parameters. In order to maximize the reaction parameters, Response Surface Methodology design was employed for experimental optimization. We use FT-IR, TGA, SEM, EDX, and XRD to investigate hydrogel formation. At 37 °C, an investigation was carried out on the in vitro controlled release of PN at pH 2, 7, and 7.4. The analysis of drug release data revealed that PM and KM exhibited an initial burst release of drugs, with the MW and FD method proving to be the most suitable approach for achieving precise ICs of PN and β-CD for sustained drug release. The kinetics of drug release were evaluated using various kinetic models, with the Riteger-Peppas and Peppas-Sahlin models demonstrating the best fit for drug release in all instances.

Keywords: Central composite design; Pectin; Phenothiazine; Pullulan and response surface methodology; β-Cyclodextrin.