Department of Pharmaceutical Technology, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
Department of Pharmaceutical Technology, School of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
Int J Pharm. 2020 Apr 15;579:119149. doi: 10.1016/j.ijpharm.2020.119149. Epub 2020 Feb 15.
The correlation between glass forming ability (GFA) and several thermophysical or physicochemical properties of APIs with the formation and the physical stability of amorphous solid dispersions (ASDs) was evaluated in the present study. Eight poorly water-soluble APIs belonging in different GFA classes (i.e. a) GFA Class I: Carbamazepine, CBZ, b) GFA Class II: Agomelatine, AGO, Aprepitant, APT, Rivaroxaban, RIV, and c) GFA Class III: Indomethacin, IND, Pioglitazone, PIO, Piroxixam, PIR, and Simvastatin, SIM) were tested, in addition to six commonly used matrix-carriers (namely povidone, PVP, hydroxypropyl cellulose, HPC-SL, copovidone, coPVP, Soluplus®, SOL, and gelatin) in order to prepared ASDs via film casting approach. Results using polarized light microscopy (PLM) showed a similar drug crystallization tendency from ASDs independently of their GFA classification, glass stability or glass fragility. X-ray diffraction analysis verified the formation and the physical stability of ASD (independently of GFA class) when a suitable matrix-carrier was selected (i.e. SOL for AGO, RIV and SIM, PVP for APT, CBZ and IND, coPVP for PIO and gelatin for PIR). Further attempts to correlate some physicochemical properties (i.e. component's binding affinity and miscibility) with the formation and the crystallization tendency of the prepared ASDs showed no apparent correlation in regards to the different drug GFA classes. Finally, the evaluation of molecular interactions via FTIR analysis also failed to adequately distinguish the differences in regards to the formation and the physical stability of the prepared systems.
本研究评估了与 API 的玻璃化转变能力（GFA）和一些热物理或物理化学性质相关的几个因素，以及它们与无定形固体分散体（ASD）的形成和物理稳定性的关系。八种属于不同 GFA 类别的疏水性差的 API（即 a）GFA 类 I：卡马西平，CBZ，b）GFA 类 II：阿戈美拉汀，AGO，阿瑞匹坦，APT，利伐沙班，RIV，和 c）GFA 类 III：吲哚美辛，IND，吡格列酮，PIO，吡罗昔康，PIR，和辛伐他汀，SIM），以及六种常用的基质载体（即聚乙烯吡咯烷酮，PVP，羟丙基纤维素，HPC-SL，共聚维酮，共聚 PVP，Soluplus®，SOL，和明胶），通过薄膜铸造法制备 ASD。使用偏光显微镜（PLM）的结果表明，无论其 GFA 分类、玻璃稳定性或玻璃脆性如何，ASD 中药物结晶的趋势相似。X 射线衍射分析证实，当选择合适的基质载体（即 SOL 用于 AGO、RIV 和 SIM、PVP 用于 APT、CBZ 和 IND、coPVP 用于 PIO 和明胶用于 PIR）时，ASD 的形成和物理稳定性。进一步尝试将一些物理化学性质（即成分的结合亲和力和混溶性）与制备的 ASD 的形成和结晶趋势相关联，结果表明，不同药物 GFA 类之间没有明显的相关性。最后，通过傅里叶变换红外（FTIR）分析评估分子相互作用也未能充分区分制备体系形成和物理稳定性方面的差异。
