Abstract
BackgroundIncreasing 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.ResultsThe 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).ConclusionIt 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.
Highlights
Increasing hydrophilicity of poorly water-soluble drugs is a major challenge in drug discovery and development
Cocrystallization is currently recognized as a successful method to improve the physicochemical properties of solid Active pharmaceutical ingredients (APIs) leading to requisite therapeutic benefit; cocrystals offer an effective optimized physicochemical and mechanical properties of the active drugs but they offer the possibility of combined therapies that come along with intellectual property opportunities [14]
Taking the advantages of drug–drug cocrystals in overcoming the problems associated with single drug therapy, reduction of dosage, CAR-HCT cocrystals were prepared
Summary
Increasing hydrophilicity of poorly water-soluble drugs is a major challenge in drug discovery and development. Present work is an attempt to improve the solubility of CAR by preparing cocrystals using hydrochlorothiazide (HCT), a diuretic drug, as coformer. Many APIs exhibit poor water solubility and dissolution rate which may correlate to their suboptimal bioavailability [1]. More it is important in case of formulating solid dosage forms of drugs by oral route as it is the most preferred and patient-friendly mode of administration. Cocrystals are solid, crystalline materials that are being used increasingly for the development of APIs with improved physicochemical properties [11,12,13,14] such as solubility, stability, and bioavailability [15, 16]. The current popularity of cocrystals need not be overemphasized as some cocrystals entered the market [Suglat® (ipragliflozin L-proline) in Japan and Entresto® (sacubitril and valsartan) in USA] and several more in late stages of development [22, 23]
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