Nebivolol Hydrochloride-Amino Acid Zwitterionic Cocrystals with Superior Physicochemical Characteristics

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Cocrystallization of drugs with coformers is a promising method for modifying drug substance solid state qualities such as solubility and dissolution. The current study aimed to create, synthesize, and analyze Nebivolol hydrochloride cocrystals by screening several coformers. The type II biopharmaceutical medication Nebivolol hydrochloride (NBH), used to treat hypertension, has great permeability, limited water solubility, and a slow dissolving rate. This remains a barrier to the creation of innovative formulations. In this paper, we focus on the formation of the first NBH zwitterionic cocrystals while using less hazardous zwitterionic amino acids as coformers, such as L-proline P) and L-glutamine (G). The zwitterionic cocrystals of NBH were synthesized using liquid-aided grinding and slow solvent evaporation procedures by using a molar ratio (1:1) of the drug and zwitterion coformers. The cocrystals revealed a distinctive characteristic in X-ray diffraction studies, FT-IR spectra, SEM images, and DSC thermograms. The infrared study demonstrated the displacement of NBH distinctive bands. The X-Ray Powder Diffraction pattern indicated co-crystallinity and a significant difference in the 2θ value of intense peaks. Differential scanning calorimetry (DSC) spectra of cocrystals revealed changed endotherms correlating to melting point. Dissolution studies revealed that the zwitterionic NBH cocrystals disintegrated faster in vitro by 89.3% and 84.7% respectively.