Preparation and physicochemical characterization of binary and ternary ground mixtures of carvedilol with PVP and SLS aimed to improve the drug dissolution

Abstract

The objective of the present study was to enhance the dissolution rate of carvedilol (CA), a poorly water-soluble antihypertensive drug, using a co-grinding method in the presence of polyvinylpyrrolidone (PVP) and sodium lauryl sulfate (SLS). Various ratios of CA:PVP:SLS were ground by a planetary ball mill. They were studied in terms of dissolution, solubility, and particle size. The solid state and morphology of the intact drug and prepared samples were also characterized using differential scanning calorimetry (DSC), infrared spectroscopy (IR), X-ray diffraction (XRD), and scanning electron microscope (SEM). According to the results, co-grinding in the presence of PVP and SLS significantly increased CA dissolution rate. DE₆₀ (dissolution efficiency) obtained for the best ternary ground mixture (89.31%) was 3.4 and 4.5 times higher than that of the related physical mixture (PM) and the intact drug, respectively. Further, the solubility of this formulation was about 10 times higher compared to that of the intact CA. A direct correlation was also observed between the chamber rotation speed of the planetary mill within the range of 100–400 rpm and CA dissolution rate. Finally, DSC, IR, and XRD analysis ruled out any polymorphic changes and chemical interactions during the grinding process.

KEYWORDS:

• Carvedilol
• co-grinding
• dissolution enhancement
• PVP
• SLS

Acknowledgments

This study was a part of Pharm D thesis registered at Shahid Beheshti University of Medical Sciences.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors would like to thank the research deputy of Shahid Beheshti University of Medical Sciences for providing the financial support to conduct this research (No. 1290).