pH-responsive chitosan based hydrogels for the simultaneous delivery of atorvastatin calcium and ezetimibe

The management of cholesterol by using Atorvastatin calcium (ATV) and Ezetimibe (EZE) is often restricted by the fact that they belong to BCS Class II drugs, thus, low aqueous solubility and low systemic bioavailability. The research has created a new pH-responsive hydrogel involving a natural polycationic polysaccharide, chitosan, to increase residence time in the sites of absorption and offer controlled, concurrent delivery of both drugs. The hydrogels were synthesized through a free-radical polymerization process, which entailed dissolving chitosan in aqueous acetic acid, initiation by ammonium persulfate (APS) and addition of acrylic acid (AA) and N,N'-methylene bisacrylamide (MBA) in drops to create a stable 3D cross-linked structure. The numerical optimization was performed with Design Expert software, in which the ratios of components are accurately tuned with the help of the use of the poly equations and 3D response surface plots. This methodology removed hit and trial error leading to a maximized formulation in which the real experimental values, including 87.98% porosity and 98.76% gel fraction, were in good agreement with the software predictions, which confirmed the strength of the design. Findings showed that the internal structure was greatly determined by the formulation parameters; the higher the monomer concentrations, the better the porosity (97.53%) and the gel fraction (97.79%). The system was also very pH-sensitive as it swelled little in acidic environment (pH 1.2) but swelled the most (187.71%) in simulated intestinal fluids (pH 6.8 and 7.2) which allowed the system to dissolve 91.99% of ATV and 90.77% of EZE within 24 h. This mathematically designed platform with dual drug delivery is designed to overcome the drawbacks of a single-drug matrix for cholesterol management and prevent premature leakage from the stomach.