Mishra Jaya, Rades Thomas, Löbmann Korbinian, Grohganz Holger
Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
Department of Pharmacy, Faculty of Science and Engineering, Abo Akademi University, 20521 Turku, Finland.
Pharmaceutics. 2018 Apr 12;10(2):47. doi: 10.3390/pharmaceutics10020047.
Ball-milling is usually used to prepare co-amorphous drug-amino acid (AA) mixtures. In this study, co-amorphous drug-AA mixtures were produced using spray-drying, a scalable industrially preferred preparation method. The influence of the solvent type and solvent composition was investigated. Mixtures of indomethacin (IND) and each of the three AAs arginine, histidine, and lysine were ball-milled and spray-dried at a 1:1 molar ratio, respectively. Spray-drying was performed at different solvent ratios in (a) ethanol and water mixtures and (b) acetone and water mixtures. Different ratios of these solvents were chosen to study the effect of solvent mixtures on co-amorphous formulation. Residual crystallinity, thermal properties, salt/partial salt formation, and powder dissolution profiles of the IND-AA mixtures were investigated and compared to pure crystalline and amorphous IND. It was found that using spray-drying as a preparation method, all IND-AA mixtures could be successfully converted into the respective co-amorphous forms, irrespective of the type of solvent used, but depending on the solvent mixture ratios. Both ball-milled and spray-dried co-amorphous samples showed an enhanced dissolution rate and maintained supersaturation compared to the crystalline and amorphous IND itself. The spray-dried samples resulting in co-amorphous samples were stable for at least seven months of storage.
球磨通常用于制备共无定形药物 - 氨基酸（AA）混合物。在本研究中，使用喷雾干燥法制备共无定形药物 - AA混合物，喷雾干燥是一种可扩展的工业上更优选的制备方法。研究了溶剂类型和溶剂组成的影响。分别将吲哚美辛（IND）与精氨酸、组氨酸和赖氨酸这三种氨基酸中的每一种按1:1摩尔比进行球磨和喷雾干燥。在（a）乙醇和水的混合物以及（b）丙酮和水的混合物中以不同的溶剂比例进行喷雾干燥。选择这些溶剂的不同比例来研究溶剂混合物对共无定形制剂的影响。研究了IND - AA混合物的残余结晶度、热性质、盐/部分盐形成以及粉末溶解曲线，并与纯结晶和无定形IND进行比较。结果发现，使用喷雾干燥作为制备方法，所有IND - AA混合物均可成功转化为各自的共无定形形式，这与所使用的溶剂类型无关，但取决于溶剂混合比例。与结晶和无定形IND本身相比，球磨和喷雾干燥的共无定形样品均显示出提高的溶解速率并保持过饱和状态。所得共无定形样品的喷雾干燥样品在储存至少七个月时是稳定的。
