Solubility enhancement of carvedilol using drug–drug cocrystallization with hydrochlorothiazide

Abstract

Background Increasing hydrophilicity of poorly water-soluble drugs is a major challenge in drug discovery and development. Cocrystallization is one of the techniques to enhance the hydrophilicity of such drugs. Carvedilol (CAR), a nonselective beta/alpha1 blocker, used in the treatment of mild to moderate congestive heart failure and hypertension, is classified under BCS class II with poor aqueous solubility and high permeability. Present work is an attempt to improve the solubility of CAR by preparing cocrystals using hydrochlorothiazide (HCT), a diuretic drug, as coformer. CAR-HCT (2:0.5) cocrystals were prepared by slurry conversion method and were characterized by DSC, PXRD, FTIR, Raman, and SEM analysis. The solubility, stability, and dissolution (in vitro) studies were conducted for the cocrystals. Results The formation of CAR-HCT cocrystals was confirmed based on melting point, DSC thermograms, PXRD data, FTIR and Raman spectra, and finally by SEM micrographs. The solubility of the prepared cocrystals was significantly enhanced (7.3 times), and the dissolution (in vitro) was improved by 2.7 times as compared to pure drug CAR. Further, these cocrystals were also found to be stable for 3 months (90 days). Conclusion It may be inferred that the drug–drug (CAR-HCT) cocrystallization enhances the solubility and dissolution rate of carvedilol significantly. Further, by combining HCT as coformer could well be beneficial pharmacologically too.

Solubility Enhancement of Carvedilol by Solid Dispersion Technique Using Sodium Alginate, Guar Gum, Xanthan Gum, and Locust Bean Gum as Polymers

“…The readings of the FTIR spectra on samples of pure CVD, polymer, physical mixture, and CVD solid dispersion were carried out separately using an FTIR spectrophotometer. FTIR spectrum readings are seen in the 4000-400 cm −1 at a resolution of 4 cm −1 [20].…”

“…The diffractogram pattern of pure CVD, physical mixture and solid dispersion of CVD was performed using an X-ray diffractometer with copper Kα radiation (wavelength = 1.54060), a voltage of 40 kV and a current of 20 mA. 100-200 mg samples were scanned in the range of 5-60° (2θ) at a speed of 0.02°/sec [20].…”

Modification of Physicochemical Properties of Active Pharmaceutical Ingredient by Pharmaceutical Co-Crystals

“…Slurry conversion was used to create CAR-HCT (2: 0.5) co-crystals, which were then analysed using DSC, PXRD, FTIR Raman and SEM. The co-crystals were the subject of solubility, stability and dissolution (in vitro) studies [87]. Kang Zheng et al presented study reports on the MNZ-PYR co-crystal, a new co-crystal of the antimicrobial drug metronidazole (MNZ) that uses pyrogallol (PYR) as a co-crystal former.…”

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“…Kept the solution on a magnetic stirrer for 24 hrs. When the equilibrium state was reached, then filtration of the solution takes place; the filtrate was collected, diluted, and observed through UV spectrophotometry at 308 nm 12 . Solubility Studies: Solubility was performed in triplicate according to Higuchi and Connors's method to evaluate the increment in the solubility of ABZ (solid dispersion).…”