Injection-Molded Coamorphous Tablets: Analysis of Intermolecular Interaction and Crystallization Propensity

• Published in: Journal of pharmaceutical sciences 2021-09, Vol.110 (9), p.3289-3297
• Main Authors: Tanaka, Ryoma, Ishihara, Sae, Sasaki, Tetsuo, Hattori, Yusuke, Otsuka, Makoto
• Format: Article
• Language: English
• Subjects: Amorphous; Coamorphous; Crystallization; Excipient; Formulation; Injection molding; Molecular interaction; Organic acid; Poorly water-soluble drug; Tablet
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1016/j.xphs.2021.05.020

The processing steps involved in converting from a powder to a tablet entail numerous operations in a which the coamorphous system is recrystallized and dissociated easily. This research focused on (i) a single-step preparation of a coamorphous tablet during injection molding (IM) from the bulk powder, and (ii) a mechanistic characterization of the coamorphous formulation. We selected several organic acids [citric acid, succinic acid, tartaric acid, and malic acid] in an effort to compound with basic loratadine (a poorly water-soluble drug). Loratadine–acids coamorphous tablets were produced via an IM process, and the dissolution was more enhanced than in the pure loratadine amorphous. The interaction was analyzed by FT-IR and terahertz spectroscopies. Each tablet was stored at 40 °C/75%RH, and then XRD patterns were acquired at the desired timepoints. In summary, loratadine exhibited ionic interaction with each acid, and the physical stability of the coamorphous tablet was in proportion to the loratadine–acids interaction strength. Terahertz spectra detected the molecular mobility, which plays an important role in the crystallization propensity of a coamorphous system. This understanding offers a framework for robust coamorphous tablet formulation using the IM methodology. [Display omitted]