Abstract
Physicochemical properties play a pivotal role in the absorption mechanism of orally administered drugs. Hydrochlorothiazide (HZT), a class IV drug inherently lacks the required solubility and permeability. In addition, the drug tends to degrade rapidly in an aqueous media. In order to eliminate these issues, different excipients were selected including beta-cyclodextrin (beta-CD), sodium lauryl sulfate (SLS), and Tween 20 which were physically mixed with HZT in order to enhance its solubility, stability, and permeability. The equilibrium aqueous solubility for HZT was successfully achieved with the selected method. beta-CD was superior to other surfactants in the extent of equilibrium solubility at 25 degrees C across the selected concentration range of (0.25-2% w/v).beta-CD was also able to increase the degradation half-life (247.5 h for 2.0% w/v beta-CD) about 28 folds compared to 3 folds for Tween 20 (32.7 h for 2.0% w/v Tween 20). Non-everted intestinal sac model showed significantly higher permeation rate for HZT as an inclusion complex (>80.0%) compared to HZT alone (47%). This study suggested that beta-CD was alone able to not only increase the solubility and permeability of HZT, but also prevent the degradation for at least 60 days at ambient temperature. (C) 2017 Elsevier B.V. All rights reserved.