米国先進ドラッグデリバリージャーナル オープンアクセス

抽象的な

Enhancement of Solubility and Bioavailability of Hydrochlorthiazide Using Solid Dispersion Technique

E. Sangeetha, Vinay Umesh Rao, M. Sudhakar and S. Manisha

Objective: The variable aqueous solubility of Hydrochlorthiazide (HCTZ) is the major factor limiting its oral bioavailability. The objective of the study is to enhance of the solubility of HCTZ by using solid dispersion technique.

Methods: The polymers used were PVP K30, PVP S630, HPMC & PEG 6000 and solid dispersions were prepared by solvent evaporation method in different ratios of 1:0.5, 1:1, 1:3, 1:5 respectively. The prepared solid dispersions were characterized by DSC and FTIR. The equilibrium solubility was determined in water to study the effect of polymers on solubility of HCTZ. In vitro dissolution studies were conducted in distilled water from solid dispersions equivalent to 12.5 mg of HCTZ. How the solid dispersions affect the permeation of the drug across membranes was evaluated by measuring the In vitro permeation of Drug PVP and Drug HPMC across cellophane membrane using the vertical Franz diffusion cell.

Results: Successful conversion of the crystalline Hydrochlorthiazide to amorphous solid dispersion was achieved at 1:1, 1:3 & 1:5 levels of drug to HPMC E 15 & drug to PVP and with PVP S630 it was achieved at 1:3 & 1:5 level. Amorphous conversion was not observed in case of PEG 6000 at any level. The solid dispersion prepared with HPMC E 15 & PVP K30 at 1:5 level showed a 98% and 66.3% drug release at 5min respectively. The enhancements in case of 1:5 Plasdone s630 and PEG 6000 were not significant. The results of equilibrium solubility studies indicates that the solvent evaporated solid dispersions of HPMC E 15 & PVP K30 were the best Permeation studies indicate that a 3 to 4 fold increase in the solubility of the drug results in 10 fold increase in permeation. Thus enhancement in solubility also results in enhancement in the permeation across artificial membranes.

Conclusion: The above study shows that solid dispersion of HCTZ offers a simple and attractive solution to increasing the solubility of the poorly water soluble drug and thereby improve its oral bioavailability.