Enhancing gliclazide solubility using solid dispersions with carboxymethyl chitosan and polyvinylpyrrolidone K30 as polymeric carriers

Abstract

Background: Gliclazide (Glz) is a second-generation sulfonylurea antidiabetic drug, used to treat type II diabetes mellitus. Glz is a class II drug according to the biopharmaceutic classification system (BCS), indicating that it has high permeability and poor aqueous solubility. Objective: This study aimed to improve the solubility of Glz via the solid dispersion method. Methods: Solid dispersions of the drug were formulated using carboxymethyl chitosan (CMch) and polyvinyl pyrrolidone K30 (PVP K30) in varying drug to carrier ratios (1:1, 1:3, and 1:5 w/w) using kneading and solvent evaporation methods. The solubility of Glz solid dispersions was compared with the pure Glz and co-grounded mixtures of the drug. Results: Both carriers exhibited a noticeable increment in solubility and dissolution rate compared to the drug alone. Glz: CMch (1:5 w/w ratio) formulation made by the kneading method exhibited an increased solubility by approximately nine folds (337.79 ± 4.22 µg/ml) as compared to Glz alone (38.74 ± 4.69 µg/ml). However, the greatest improvement in drug dissolution rate was observed in the dispersion made with 1:5 w/w drug to PVP K30 using the solvent evaporation method, and the percentage drug release reached 100% after 30 min. Solid dispersions characterization manifested the compatibility between the drug and carriers, with alteration in particle morphology, and reduction in drug crystallinity. Conclusion: Overall, solid dispersion using CMch has shown to be an excellent approach for enhancing the solubility and dissolution of the class II drug Glz.