Formulation, Optimization and Characterization of Chitosan Monodisperse Microparticles for Sustained Delivery of Hydrochlorothiazide HCl

Abstract

Background: Hydrochlorothiazide HCl (HCTZ) is first line medication in the management of hypertension, however its poor solubility and GI irritation warrants long term application. The aim of present study was to prepare hydrochlorothiazide HCl (HCTZ) loaded monodisperse microparticles of chitosan (CS) for sustained delivery. Methods: In the present study chitosan microparticle were prepared using ionic gelation method. The effect of input parameters such as concentration of chitosan and pH of CS solution on the mean particle size (PS), zeta potential (ZP), polydispersity index (PDI) and in-vitro drug release were investigated. In-vitro drug release from the microparticles was studied using Franz diffusion cell. Structural formation and surface morphology was investigated using FTIR and SEM, respectively. Results: PS of CS microparticles ranges from 0.878±0.066 to 1.963±0.011 µm, ZP between 33.43±0.80 mV to 53.6±2.06 mV, PDI values from 0.271±0.063 to 0.842±0.073. The optimized CSMP- 3 (1.5% chitosan, pH 3) showed PS 1.672 ± 0.073 µm, ZP 53.6 ±2.06 mV, PdI 0.481±0.053, %EE 80.8±2.27% and HCTZ release of around 80% in 8 hours. FTIR reveals successful formation of crosslinked structure. SEM shows irregular surface owing preparation procedure. Drug kinetics modeled with Korsemeyer–Peppas equation revealed non-Fickian diffusion mechanism. Conclusion: Drug permeation study showed more than 70% of drug permeated through membrane. In conclusion, the CS microparticles can be used for the sustained delivery of HCTZ which would reduce the dosing frequency and improved patient compliance.

Keywords

• hydrochlorothiazide
• microparticles
• permeation
• chitosan
• sustained release