Pharmaceutical cocrystals of nebivolol hydrochloride with enhanced solubility

•Nebivolol hydrochloride is an antihypertensive BCS class II drug.•Cocrystals with 4-hydroxy benzoic acid and nicotinamide were prepared.•Liquid assisted grinding and solvent evaporation method was used.•The problem of low solubility and dissolution can be solved with cocrystals. Nebivolol hydrochlo...

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Veröffentlicht in:Journal of crystal growth 2020-03, Vol.534, p.125488, Article 125488
Hauptverfasser: Nikam, Vilas J., Patil, Sanjay B.
Format: Artikel
Sprache:eng
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Zusammenfassung:•Nebivolol hydrochloride is an antihypertensive BCS class II drug.•Cocrystals with 4-hydroxy benzoic acid and nicotinamide were prepared.•Liquid assisted grinding and solvent evaporation method was used.•The problem of low solubility and dissolution can be solved with cocrystals. Nebivolol hydrochloride is BCS class II drug with low solubility and high permeability prescribed as antihypertensive. Crystal engineering was applied to prepare novel cocrystal forms of nebivolol hydrochloride with general GRAS (Generally regarded as safe) molecules. Pharmaceutical cocrystals of nebivolol hydrochloride were prepared with GRAS molecules, such as 4-hydroxybenzoic acid and nicotinamide (NA), with different ratios like 1:1, 1:2, 1:3. Liquid assisted grinding and solvent evaporation method was used to prepare nebivolol hydrochloride cocrystals. All prepared crystalline forms were characterized by X-ray diffraction, differential scanning calorimetry, and FT-IR to confirm their purity and formation of cocrystals. X-ray crystal data provided details of hydrogen bonding and interactions between drug and co-formers and differential scanning calorimetry provided changes in thermal behaviour and formation of cocrystals. Physicochemical properties such as solubility and dissolution rate were measured and found that all the co-crystals dissolved faster and their equilibrium solubility is higher than the parent drug. Nebivolol hydrochloride - 4-hydroxy benzoic acid cocrystals showed highest solubility among all crystalline forms.
ISSN:0022-0248
1873-5002
DOI:10.1016/j.jcrysgro.2020.125488