RC Patel Institute of Pharmaceutical Education and Research, Karvand Naka, Shirpur, Dist. Dhule, Maharashtra, India.
Pharm Dev Technol. 2013 Jul-Aug;18(4):844-51. doi: 10.3109/10837450.2011.591802.
Lactose is used as an excipient in solid dosage forms of nebivolol. Ultraviolet spectroscopy, Fourier-transform infrared spectroscopy and differential scanning calorimetry were used to study the interaction between nebivolol and lactose. The formation of a Maillard product was noted in aqueous mixtures of nebivolol and lactose heated at 60°C at unbuffered and buffered alkaline pH. A similar Maillard adduct formation was evident within 15 days in a dry physical mixture of nebivolol and lactose maintained at 40°C and 75% relative humidity in the dark. High-performance liquid chromatography and liquid chromatography-mass spectrometry analyses of the reaction mixtures confirmed the formation of a nebivolol-lactose adduct. The effects of intravenously administered nebivolol and the nebivolol-lactose adduct on the blood pressure and heart rate of anesthetized normotensive rats were investigated. The bradycardic effect of the adduct was significantly less than that of nebivolol. The present investigation reveals an incompatibility between nebivolol and lactose, leading to the loss of the pharmacological activity of nebivolol. Hence, the use of lactose as an excipient in dosage forms of nebivolol, a secondary amine, needs reconsideration.
乳糖被用作 nebivolol 的固体剂型中的赋形剂。使用紫外光谱法、傅里叶变换红外光谱法和差示扫描量热法研究 nebivolol 与乳糖之间的相互作用。在 60°C 加热的 nebivolol 和乳糖的水混合物中，在未缓冲和缓冲碱性 pH 下注意到美拉德产物的形成。在黑暗中于 40°C 和 75%相对湿度下保持的 nebivolol 和乳糖的干物理混合物中，在 15 天内也可以明显看出类似的美拉德加合物形成。反应混合物的高效液相色谱和液质联用分析证实了 nebivolol-乳糖加合物的形成。研究了静脉给予 nebivolol 和 nebivolol-乳糖加合物对麻醉正常血压大鼠的血压和心率的影响。加合物的降心率作用明显小于 nebivolol。本研究揭示了 nebivolol 与乳糖之间的不兼容性，导致 nebivolol 的药理活性丧失。因此，需要重新考虑乳糖作为 nebivolol 等仲胺类药物剂型中的赋形剂的用途。
