title: Physicochemical Evaluation and Developability Assessment of Co-amorphouses of Low Soluble Drugs and Comparison to the Co-crystals.
abstract: To judge the developability and analyze functional mechanism of co-amorphouses, we investigated the physicochemical properties of co-amorphouses and compare the properties with the co-crystals having the same drug and counters. Co-amorphous compounds are a novel approach to improve the physicochemical properties of drugs. A co-amorphous is in an amorphous solid state allowing non-ionic interactions between drug molecules and counter molecules. The co-amorphous compounds composed of itraconazole (ITZ) with the organic carboxyl acid, fumaric acid (FA) or L-tartaric acid (TA), were prepared by mechanical grinding. Potential interactions within ITZ-FA co-amorphous were assessed by Raman spectroscopy. ITZ-FA co-amorphous was not crystallized as the co-crystal or as a single ITZ crystal, suggesting that the amorphous state, like the amorphous solid dispersion, was physically stable and that ITZ-FA co-amorphous was also chemically stable. In contrast, no clear interactions were observed within ITZ-TA co-amorphous, and the co-amorphous was physically stable but chemically unstable. The solubility of the co-amorphous state was much higher than those of ITZ crystal and the co-crystals and was almost identical to that of amorphous ITZ. A co-amorphous compound like ITZ-FA co-amorphous might be feasible to implement in the development of solid drug products and bring some merits compared to the co-crystals, and the function is governed by the interaction between a drug and a counter. The co-amorphous approach may be an effective strategy for drug development and can contribute to the production of novel drugs with improved functions.
authors.affiliation: Analytical Development, Pharmaceutical Sciences, Takeda Pharmaceutical Company Limited.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Taro
authors.initials: T
authors.lastname: Kojima
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Karashima
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Ikeda
mesh_terms: D002384:Catalysis; D002627:Chemistry, Physical; D003035:Cobalt / Q000737:chemistry*; D003460:Crystallization; D005650:Fumarates / Q000737:chemistry*; D017964:Itraconazole / Q000737:chemistry*; D015394:Molecular Structure; D012995:Solubility; D013644:Tartrates / Q000737:chemistry*
chemical_list: D005650:Fumarates; D013644:Tartrates; D017964:Itraconazole; D003035:Cobalt; C032005:fumaric acid; C029768:tartaric acid