Structural evaluation of drug solution by ATR terahertz, NMR, DSC, and viscometry

• Project/Area Number: 21590038
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Physical pharmacy
• Research Institution: Chiba University
• Principal Investigator: MORIBE Kunikazu 千葉大学, 大学院・薬学研究院, 准教授 (50266350)
• Co-Investigator(Kenkyū-buntansha): YAMAMOTO Keiji 千葉大学, 大学院・薬学研究院, 教授 (50110341) ; HIGASHI Kenjirou 千葉大学, 大学院・薬学研究院, 助教 (40451760)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2009: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
• Keywords: 溶液構造 / 相互作用 / NMR / 原子間力顕微鏡 / テラヘルツ / 溶液 / 分子状態 / ナノ微粒子 / 可溶化 / 構溶液造

Research Abstract

Physicochemical characterization of poorly water-soluble drug nanosuspension and the aqueous solution prepared by the cogrinding with pharmaceutical excipients was demonstrated. Dispersive state of drug nanoparticles as well as molecular state of drug and excipients in aqueous media was well demonstrated. Composition-dependent size changes were observed for drug nanoparticles prepared by cogrinding or solvent evaporation. Combined methods of suspended state NMR combined and liquid state NMR were useful to evaluate molecular states of stable drug nanosuspension. Drug supersaturated solution and drug solubilized solution were investigated by NMR measurements. We conclude that NMR techniques are the promising method to evaluate molecular interaction between drug and excipients as well as the mobility.

Research Products

• [Journal Article] Molecular-level characterization ofprobucol nanocrystal in water by insitu solid-state NMR spectroscopy. (2012)
  • Author(s): J. Zhang, K. Higashi, W. Limwikrant, K. Moribe, K. Yamamoto
  • Journal Title: Int. J. Pharm Volume: 423 Pages: 571-576
• [Journal Article] Structural evaluation of probucol nano particles in water by atomic force microscopy (2012)
  • Author(s): K. Moribe, W. Limwikrant, K. Higashi, K. Yamamoto
  • Journal Title: Int J Pharm Volume: 427 Pages: 365-371
• [Journal Article] Stabilization of a Supersaturated Solution of Mefenamic Acid from a Solid Dispersion with EUDRAGIT(R)EPO (2012)
  • Author(s): Kojima, K. Higashi, T. Suzuki, K. Tomono, K. Moribe, K. Yamamoto
  • Journal Title: Pharm Res
• [Journal Article] Molecular-level characterization of probucol nanocrystal in water by in situ solid-state NMR spectroscopy (2012)
  • Author(s): J.Zhang, K.Higashi, W. Limwikrant, K.Moribe, K.Yamamoto
  • Journal Title: Int J Pharm Volume: 423 Issue: 2 Pages: 571-576
  • DOI: 10.1016/j.ijpharm.2011.11.028
  • Peer Reviewed
• [Journal Article] Structural evaluation of probucol nanoparticles in water by atomic force microscopy (2012)
  • Author(s): K.Moribe, W.Limwikrant, K.Higashi, K.Yamamoto
  • Journal Title: Int J Pharm Volume: 427 Issue: 2 Pages: 365-371
  • DOI: 10.1016/j.ijpharm.2012.02.020
  • Peer Reviewed
• [Journal Article] Stabilization of a Supersaturated Solution of Mefenamic Acid from a Solid Dispersion with EUDRAGIT([○!R]) EPO (2012)
  • Author(s): T.Kojima, K.Higashi, T.Suzuki, K.Tomono, K.Moribe, K. Yamamoto
  • Journal Title: Pharm Res Volume: (印刷中) Issue: 10 Pages: 2777-2791
  • DOI: 10.1007/s11095-011-0655-7
  • Peer Reviewed
• [Journal Article] Structural evaluation of crystalline ternaryγ-cyclodextrin complex (2011)
  • Author(s): K. Higashi, S. Ideura, H. Waraya, K. Moribe, K. Yamamoto
  • Journal Title: J. Pharm.Sci Volume: 100 Pages: 325-333
• [Journal Article] Guest molecular size-dependent inclusion complexation of parabens with cholic acid by cogrinding (2011)
  • Author(s): K. Moribe, M. Masaki, R. Kinoshita, J. Zhang, W. Limwikrant, K. Higashi, Y. Tozuka, T. Oguchi, K. Yamamoto
  • Journal Title: Int. J. Pharm Volume: 420 Pages: 191-197
• [Journal Article] NMR investigation of a novel excipient, α-glucosylhesperidin, as a suitable solubilizing agent for poorly water-soluble drugs (2011)
  • Author(s): J. Zhang, Y. Tozuka, H. Uchiyama, K. Higashi, K. Moribe, H. Takeuchi, K. Yamamoto
  • Journal Title: J. Pharm.Sci Volume: 100 Pages: 4421-4431
• [Journal Article] NMR investigation of a novel excipient, α-glucosylhesperidin, as a suitable solubilizing agent for poorly water-soluble drugs (2011)
  • Author(s): J.Zhang, Y.Tozuka, H.Uchiyama, K.Higashi, K.Moribe, H.Takeuchi, K.Yamamoto
  • Journal Title: J.Pharm.Sci Volume: 100 Issue: 10 Pages: 4421-4431
  • DOI: 10.1002/jps.22606
  • Peer Reviewed
• [Journal Article] Guest molecular size-dependent inclusion complexation of parabens with cholic acid by cogrinding (2011)
  • Author(s): K.Moribe, M.Masaki, R.Kinoshita, J.Zhang, W.Limwikrant, K.Higashi, Y.Tozuka, T.Oguchi, K.Yamamoto
  • Journal Title: Int.J.Pharm Volume: 420 Issue: 2 Pages: 191-197
  • DOI: 10.1016/j.ijpharm.2011.08.027
  • Peer Reviewed
• [Journal Article] Structural evaluation of crystalline ternary γ-cyclodextrin complex. (2011)
  • Author(s): K.Higashi, S.Ideura, H.Waraya, K.Moribe, K.Yamamoto
  • Journal Title: J.Pharm.Sci. Volume: 100 Pages: 325-333
  • Peer Reviewed
• [Journal Article] Ascorbyl dipalmitate/PEG-lipid nanoparticles as a novel carrier for hydrophobic drugs (2010)
  • Author(s): K. Moribe, S. Maruyama, Y. Inoue, T. Suzuki, T. Fukami, K. Tomono, K. Higashi, Y. Tozuka, K. Yamamoto
  • Journal Title: Int. J. Pharm Volume: 387 Pages: 236-243
• [Journal Article] Effect of particle size on skin permeation and retention of piroxicam in aqueous suspension (2010)
  • Author(s): K. Moribe, M. Shibata, T. Furuishi, K. Higashi, K. Tomono, K. Yamamoto
  • Journal Title: Chem. Pharm. Bull Volume: 58 Pages: 1096-1099
  • NAID: 130000299822
• [Journal Article] Simultaneous dissolution of naproxen and flurbiprofen from anovel ternary gamma-cyclodextrin complex (2010)
  • Author(s): K. Higashi, S. Ideura, H. Waraya, W. Limwikrant, K. Moribe, K. Yamamoto
  • Journal Title: Chem. Pharm. Bull Volume: 58 Pages: 769-772
• [Journal Article] alicylicacid/γ-cyclodextrin2:1 and 4:1 complex formation by sealed-heating method (2010)
  • Author(s): K. Higashi, Y. Tozuka, K. Moribe, K. Yamamoto
  • Journal Title: J. Pharm. Sci Volume: 99 Pages: 4192-4200
• [Journal Article] Effect of particle size on skin permeation and retention of piroxicam in aqueous suspension (2010)
  • Author(s): K.Moribe, M.Shihata, T.Furuishi, K.Higashi, K.Tomono, K.Yamamoto
  • Journal Title: Chem.Pharm.Bull. Volume: 58 Pages: 1096-1099
  • NAID: 130000299822
  • Peer Reviewed
• [Journal Article] Simultaneous dissolution of naproxen and flurbiprofen from a novel ternary gamma-cyclodextrin complex. (2010)
  • Author(s): K.Higashi, S.Ideura, H.Waraya, W.Limwikrant, K.Moribe, K.Yamamoto
  • Journal Title: Chem.Pharm.Bull. Volume: 58 Pages: 769-772
  • NAID: 130000255846
  • Peer Reviewed
• [Journal Article] Ascorbyl dipalmitate/PEG-lipid nanoparticles as a novel carrier for hydrophobic drugs (2010)
  • Author(s): K.Moribe, S.Maruyama, Y.Inoue, T.Suzuki, T.Fukami, K.Tomono, K.Higashi, Y.Tozuka, K.Yamamoto
  • Journal Title: Int.J.Pharm. 387 Pages: 236-243
  • Peer Reviewed
• [Journal Article] Nanoparticle formation from probucol/PVP/sodium alkyl sulfate co-ground mixture (2009)
  • Author(s): C. Wanawongthai, A. Pongpeerapat, K. Higashi, Y. Tozuka, K. Moribe, K. Yamamoto
  • Journal Title: Int. J.Pharm Volume: 376 Pages: 169-75
• [Journal Article] Prednisolone multicomponent nanoparticle preparation by aerosol solvent extraction system (2009)
  • Author(s): K. Moribe, M. Fukino, Y. Tozuka, K. Higashi, K. Yamamoto
  • Journal Title: Int. J. Pharm Volume: 380 Pages: 201-205
• [Journal Article] Characterization of ofloxacin-oxalic acid complex byPXRD, NMR, and THz spectroscopy (2009)
  • Author(s): W. Limwikrant, K. Higashi, K. Yamamoto, K. Moribe
  • Journal Title: Int. J. Pharm Volume: 382 Pages: 50-55
• [Journal Article] Nanoparticle formation from probucol/PVP/sodium alkyl sulfate co-ground mixture (2009)
  • Author(s): C.Wanawongthai, A.Pongpeerapat, K.Higashi, Y.Tozuka, K.Moribe, K.Yamamoto
  • Journal Title: Int.J.Pharm. 376 Pages: 169-175
  • Peer Reviewed
• [Journal Article] Prednisolone multicomponent nanoparticle preparation by aerosol solvent extraction system. (2009)
  • Author(s): K.Moribe, M.Fukino, Y.Tozuka, K.Higashi, K.Yamamoto
  • Journal Title: Int.J.Pharm. 380 Pages: 201-205
  • Peer Reviewed
• [Journal Article] Characterization of ofloxacin-oxalic acid complex by PXRD, NMR, and THz spectroscopy (2009)
  • Author(s): W.Limwikrant, K.Higashi, K.Yamamoto, K.Moribe
  • Journal Title: Int.J.Pharm. 382 Pages: 50-55
  • Peer Reviewed
• [Presentation] Structural evaluation of probucol nano suspension by AFM (2011)
  • Author(s): K.Moribe, W.Limwikrant, K.Higashi, K.Yamamoto.
  • Organizer: Asian Federation for Pharmaceutical Sciences Conference 2011
  • Place of Presentation: Kuala Lumpur, Malaysia
  • Year and Date: 2011-12-11
• [Presentation] 溶液中での薬物及び添加剤の物性評価 (2011)
  • Author(s): 森部久仁一
  • Organizer: 日本薬剤学会経口吸収フォーカスグループ第2回合宿討論会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-06
• [Presentation] Physicochemical characterization of drug nanoparticles in solid and suspended states (2011)
  • Author(s): K. Moribe
  • Organizer: Particulate Processes in the Pharmaceutical Industry III
  • Place of Presentation: Goldcoast, Australia
  • Year and Date: 2011-07-27
• [Presentation] Physicochemical characterization of drug nanoparticles in solid and suspended states (2011)
  • Author(s): K.Moribe
  • Organizer: Particulate Processesin the Pharmaceutical Industry III
  • Place of Presentation: Gold Coast, Australia(招待講演)
  • Year and Date: 2011-07-27
• [Presentation] 混合粉砕による薬物のナノ粒子化と製剤応用 (2011)
  • Author(s): 森部久仁一
  • Organizer: 第48回 薬剤学懇談会研究討論会
  • Place of Presentation: かみの山、山形(招待講演)
  • Year and Date: 2011-07-07
• [Presentation] Structural investigation of supersaturated solution from solid dispersion of mefenamic acid and Eudragit EPO (2011)
  • Author(s): K. Moribe, T. Kojima, K. Higashi, T. Suzuki, K. Tomono., K. Yamamoto
  • Organizer: International Symposium on BA/BE of Oral Drug Products. P11
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2011-07-01
• [Presentation] FM測定による製剤のナノ構造評価 (2011)
  • Author(s): 森部久仁一
  • Organizer: 日本薬剤学会第26年会、シンポジウム「界面化学で理解する経口吸収」
  • Place of Presentation: 東京
  • Year and Date: 2011-05-29
• [Presentation] AFM測定による製剤のナノ構造評価 (2011)
  • Author(s): 森部久仁一
  • Organizer: 日本薬剤学会第26年会
  • Place of Presentation: 船堀、東京
  • Year and Date: 2011-05-29
• [Presentation] Structural evaluation of probucol nano suspension by AFM (2011)
  • Author(s): K. Moribe, W. Limwikrant, K. Higashi, K. Yamamoto
  • Organizer: AsianFederation for Pharmaceutical Sciences Conference 2011. BO-005
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2011-05-24
• [Presentation] Preparation and physicochemical characterization of ofloxacin-dicarboxylic acid complex (2011)
  • Author(s): K.Moribe, W.Limwikrant, K.Higashi, K.Yamamoto
  • Organizer: International Congress of Analytical Sciences 2011
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2011-05-24
• [Presentation] くすりの溶解について (2011)
  • Author(s): 森部久仁一
  • Organizer: 日本薬剤学会経口吸収フォーカスグループ第1回合宿討論会
  • Place of Presentation: 沼津
  • Year and Date: 2011-02-15
• [Presentation] EVALUATION OF DRUG NANOPARTICLES IN SOLID AND SDSPENSION BY HIGH RESOLUTION SEM AND LIQUID AFM (2010)
  • Author(s): K.Moribe, C.Wanawongthai, K.Higashi, K.Yamamoto
  • Organizer: AAPS-FIP World Congress 2010
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2010-11-19
• [Presentation] Evaluation of Drug Nanoparticles in Aqueous Solution by AFM Image and Force Curve Analysis (2010)
  • Author(s): K. Moribe, A. Ogino, K. Higashi, K. Yamamoto
  • Organizer: FIP Pharmaceutical Sciences 2010 World Congress, New Orleans, M1329
  • Place of Presentation: LA, USA
  • Year and Date: 2010-11-15
• [Presentation] 薬物/(PEG-v-CD-polypseudorotaxane)複合体の構造変化が薬物の分子状態に及ぼす影響 (2010)
  • Author(s): 藁谷美香, 東顕二郎, 森部久仁一, 山本恵司
  • Organizer: 第27回シクロデキストリンシンポジウム
  • Place of Presentation: 金沢市文化ホール
  • Year and Date: 2010-09-06
• [Presentation] 3成分シクロデキストリセ複合体形成によるflurbiprofenの溶出制御 (2010)
  • Author(s): 東顕二郎, 出浦小織, 森部久仁一, 山本恵司
  • Organizer: 第27回シクロデキストリンシンポジウム
  • Place of Presentation: 金沢市文化ホール
  • Year and Date: 2010-09-06
• [Presentation] アスコルビン酸誘導体/DSPE-PEGナノ微粒子の構造評価及び細胞障害性 (2010)
  • Author(s): 森部久仁一, 壬生総子, 齋藤謙悟, 東顕二郎, 白澤浩, 山本恵司
  • Organizer: 第26回日本DDS学会2-B-23
  • Place of Presentation: 大阪
  • Year and Date: 2010-06-18
• [Presentation] Ascorbyl dipalmitate/DSPE-PEG nanoparticulate system as a novel drug delivery carrier (2009)
  • Author(s): K. Moribe, S. Maruyama, K. Higashi, K. Yamamoto
  • Organizer: 2009 American Association Pharmaceutical Sciences Annual Meeting and Exposition,W4246, Los angles
  • Place of Presentation: California, USA
  • Year and Date: 2009-11-11
• [Presentation] A Novel Complex Formation of salicylic acid and Y-cyclodextrin-polypseudorotaxane (2009)
  • Author(s): K. Higashi, H. Waraya, K. Moribe, K. Yamamoto
  • Organizer: Asian Federation for Pharmaceutical Sciences
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 2009-10-17
• [Presentation] Physicochemical characterization of phenytoin derivative nanoparticles prepared by cogrinding (2009)
  • Author(s): K. Moribe, A. Ogino, K. Higashi, K. Yamamoto
  • Organizer: Pharmaceutical Sciences
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 2009-10-17
• [Presentation] PHYSICOCHEMICAL CHARACTERIZATION OF PHENYTOIN DERIVATIVE NANOPARTICLES PREPARED BY COGRINDING (2009)
  • Author(s): K.Moribe, A.Ogino, K.Higashi, K.Yamamoto
  • Organizer: Asian Federation of Pharmaceutical Science
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 2009-10-17
• [Presentation] Drug-loaded ascorbyl dipalmitate/DSPE-PEG nanoparticulate system (2009)
  • Author(s): S. Maruyama, K. Moribe, T. Suzuki, K. Tomono, K. Higashi, K. Yamamoto
  • Organizer: 11^<th>International Symposium on Microencapsulation
  • Place of Presentation: Naogya,Japan
  • Year and Date: 2009-09-30
• [Presentation] Drug-loaded Ascorbyl dipalmitate/DSPE-PEG nanoparticulate system (2009)
  • Author(s): K.Moribe, S.Maruyama, K.Higashi, Y.Tozuka, K.Yamamoto
  • Organizer: 17^<th> International Symposium of Microencapsulation
  • Place of Presentation: Nagoya, Japan
  • Year and Date: 2009-09-29
• [Remarks]
  • URL: http://www.p.chiba-u.ac.jp/lab/seizai/index.html