Zhang Man, Xiong Xinnuo, Suo Zili, Hou Quan, Gan Na, Tang Peixiao, Ding Xiaohui, Li Hui
School of Chemical Engineering, Sichuan University Chengdu Sichuan 610065 China
RSC Adv. 2019 Jan 29;9(7):3946-3955. doi: 10.1039/c8ra09710k. eCollection 2019 Jan 25.
The preparation of co-amorphous drug systems by adding a small molecular excipient is a promising formulation in the modern pharmaceutical industry to improve the solubility, dissolution rate, and bioavailability of poorly soluble drugs. In this study, palbociclib co-amorphous systems with organic acids (succinic, tartaric, citric, and malic acid) at molar ratios of 1 : 1 were prepared by co-milling and characterized by differential scanning calorimetry (DSC), fourier transform infrared spectroscopy (FTIR) and solid-state nuclear magnetic resonance (SS-NMR). These solid-state investigations have confirmed the formation of co-amorphous salts between PAL and organic acids. The solubility, dissolution rate and stability of the four co-amorphous drug systems were significantly improved compared with these of crystalline and amorphous palbociclib. The biosafety of the co-amorphous drug systems was the same as that of palbociclib without affecting the efficacy of the drug and eliciting toxic side effects. These comprehensive approaches for the palbociclib-acid co-amorphous drug systems provided a theoretical basis for its clinical applications.
通过添加小分子辅料制备共无定形药物体系是现代制药行业中一种很有前景的制剂方法，可提高难溶性药物的溶解度、溶出速率和生物利用度。在本研究中，通过共研磨制备了帕博西尼与有机酸（琥珀酸、酒石酸、柠檬酸和苹果酸）摩尔比为1∶1的共无定形体系，并采用差示扫描量热法（DSC）、傅里叶变换红外光谱法（FTIR）和固态核磁共振（SS-NMR）对其进行了表征。这些固态研究证实了帕博西尼（PAL）与有机酸之间形成了共无定形盐。与结晶态和无定形态帕博西尼相比，四种共无定形药物体系的溶解度、溶出速率和稳定性均有显著提高。共无定形药物体系的生物安全性与帕博西尼相同，不影响药物疗效，也未引发毒副作用。这些针对帕博西尼-酸共无定形药物体系的综合研究方法为其临床应用提供了理论依据。
