| Project/Area Number |
16K18859
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Physical pharmacy
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| Research Institution | Chiba University |
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Principal Investigator |
Ueda Keisuke 千葉大学, 大学院薬学研究院, 助教 (40755972)
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| Research Collaborator |
Moribe Kunikazu
Higashi Kenjirou
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 混合粉砕 / 非晶質 / ナノ結晶 / 固体NMR / 緩和時間測定 / 難水溶性薬物 / ナノ粒子 / 製剤 / 薬物ナノ結晶 |
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| Outline of Final Research Achievements |
The co-grinding of nifedipine (NIF) with polymers, including hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP), and sodium dodecyl sulfate (SDS) was performed to prepare the NIF nanoparticle formulations. Solid-state NMR measurements revealed that the crystal size of NIF was reduced to several tens of nm with amorphization of NIF by co-grinding with HPMC and SDS for 100 min. Similarly, the size of the NIF crystal was reduced to less than 90 nm in the 40-min ground mixture of NIF/PVP/SDS. Furthermore, 100-min grinding of NIF/PVP/SDS induced amorphization of almost all the NIF crystals followed by nano-sizing. Excess amorphization of the NIF crystals failed to efficiently prepare the NIF nanoparticles. In contrast, the efficient nano-sizing of the NIF crystal in the solid state, revealed by the solid-state NMR relaxation time measurements, enabled the formation of large amounts of NIF nanoparticles in water followed by the polymer dissolution.
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| Academic Significance and Societal Importance of the Research Achievements |
分子レベルでの物性評価に基づく製剤設計により、非晶質化及びナノ結晶化の利点を最大限に引き出した製剤開発が可能となり、これまでトライ＆エラーであった薬物の非晶質化及びナノ結晶化を利用した超難水溶性薬物の特殊製剤設計に新たな指針を示すことが出来る。さらには、本新規製剤開発により、従来の固体分散体製剤及びナノ結晶製剤では十分な薬効が得られない超難水溶性薬物の経口吸収製剤開発の効率化が期待される。現在も技術革新によりNMRの感度は向上しており、将来本研究が指針となり、各種固体NMR応用測定を用いた製剤中の分子レベルでの物性評価に基づく製剤設計が可能となることが期待される。
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