Evaluation of different methods for enhancing solubility and dissolution rate of carvedilol

Abstract

Solubility measurement and dissolution rate of drugs in different solvents are the key elements of their characterizations during drug discovery processes. A number of methodologies can be adapted to improve that, further to improve its bioavailability.

Aims: Determining the solubility ofcarvedilol (CVD), and checking the predictability of some mathematical methods are the most important aims of this research.

Method and materials: In this studythe solubility ofCVD a nonselective beta-blocker in binarymixtures of (ethanol + propylene glycol (PG)) at different temperatureswere reported. The modified versions of the van’t Hoff and Gibbs equations were used to calculate the thermodynamic properties (enthalpy (ΔH°), entropy (ΔS°), and Gibbs energy (ΔG°) standard free energy changes of solutions) for CVD dissolved in (ethanol (1) + PG (2)) mixtures from the solubility data. Result and discussion: The solubility data of CVD in (ethanol (1) + PG (2)) at different temperatures were correlated using different mathematical models, i.e., the Jouyban−Acree model, a combination of the Jouyban−Acree model with the van’t Hoff model, and two modified versions of the Jouyban−Acree model. Solubility data of drug were used to develop a quantitativestructure−property relationship model for predicting solubility in solvent mixtures. In addition, enthalpy−entropy compensation using ΔH° vs ΔG° and ΔH° vs TΔS° which explains the mechanism of cosolvency at different temperatures was discussed. The last part of this thesis has been designed to serve as a quick reference for cardiovascular drugs solubility collected from literature. Conclusion: The solubility of CVD increased in the solvent mixtures in addition increased temperature lead to enhanced solubility. Also the measured data were used to evaluate the prediction capability and checking the previous mathematical methods.