Enhancement of the dissolution profile of the diuretic hydrochlorothiazide by elaboration of microspheres

Abstract

Hydrochlorothiazide (HCTZ), which was developed and introduced in the late 1950s, is still one of the most frequently employed drugs in anti-hypertensive treatments. Its poor aqueous solubility is one of the reasons for its limited bioavailability after oral administration. The present paper provides details of the preparation of HCTZ-loaded microspheres by the solvent evaporation technique. A total of seven formulations were prepared using ethyl cellulose, poly(ε-caprolactone) (PCL), β-cyclodextrin (β-CD) and synthesized poly-(methyl methacrylate) (PMMA) of different molecular weights in different drug-to-carrier ratios in order to investigate their effect on the encapsulation efficiency and drug release kinetics. The prepared formulations were characterized by Fourier transform-infrared (FTIR) spectroscopy, powder X-ray dif-fractometry, differential scanning calorimetry, yield, drug loading, optical microscopy, surface morphology by scanning electron microscopy (SEM), and in vitro release studies in simulated gastrointestinal tract fluid. The loading efficiency was found in the range from 18±0.34 to 39±0.95 %. The microspheres were spherical, and the mean Sauter diameter (d32) of the obtained microparticles ranged from 26±0.16 to 107±0.58 μm. The presence of the drug and polymer carriers in the microparticles was confirmed by FTIR spectroscopy and XRD analysis. In vitro dissolution studies showed that the release rate was largely affected by the characteristics of the microparticles, namely the particle size and the nature of the matrix. The release data are best fitted to the Higuchi model with high correlation coefficients (r2).