Evaluation of Maltose-Induced Chemical Degradation at the Interface of Bilayer Tablets
| Autor: | Naoya Matsuzaki, Daisuke Murayama, Shigeru Itai, Yousuke Yamamoto, Yasunori Iwao, Yoshifumi Katakawa, Shin-ichiro Kimura, Hisashi Mimura |
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| Rok vydání: | 2017 |
| Předmět: |
030226 pharmacology & pharmacy
01 natural sciences High-performance liquid chromatography 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Drug Stability Drug Discovery Sugar Maltose Chemical decomposition Active ingredient Chromatography Molecular Structure Hydroxypropyl cellulose Bilayer 010401 analytical chemistry General Chemistry General Medicine Solifenacin Succinate 0104 chemical sciences Thiazoles chemistry Chemical stability Acetanilides Tablets |
| Zdroj: | Chemicalpharmaceutical bulletin. 65(5) |
| ISSN: | 1347-5223 |
| Popis: | Fixed dose combination tablets consisting of mirabegron (MB) and solifenacin succinate (SS) were developed and formulated into bilayer tablets in the current study. The results of a chemical stability study showed that the original formulation for the tablets led to a significant increase of unknown degradants in the SS layer. Two compatibility studies were conducted to simulate the interface between the MB and SS layers, and the results revealed that the degradants only formed in the presence of both active pharmaceutical ingredients (APIs), and that the presence of maltose in the SS layer was critical to inducing degradation. High resolution mass spectroscopy coupled with high performance liquid chromatography was used to determine the chemical structures of the degradants, which were identified to MB derivatives bearing one or two sugar units. These findings therefore suggested that the degradation of the API could be attributed to the addition of sugar units from maltose to MB under the acidic conditions caused by SS. With this in mind, we developed a new formulation by replacing maltose with hydroxypropyl cellulose as a polymer-type binder. The results showed that this formulation suppressed the formation of the degradants. The results of this study have shown that chemical degradation can occur at the interface of bilayer tablets and that an alternative strategy is available to formulate more stable MB/SS bilayer tablets. |
| Databáze: | OpenAIRE |
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