title: Encapsulation of poorly water-soluble drugs into organic nanotubes for improving drug dissolution.
abstract: Hydrocortisone (HC), a poorly water-soluble drug, was encapsulated within organic nanotubes (ONTs), which were formed via the self-assembly of N-{12-[(2-α,β-d-glucopyranosyl) carbamoyl]dodecanyl}-glycylglycylglycine acid. The stability of the ONTs was evaluated in ten organic solvents, of differing polarities, by field emission transmission electron microscopy. The ONTs maintained their stable tubular structure in the highly polar solvents, such as ethanol and acetone. Furthermore, solution-state (1)H-NMR spectroscopy confirmed that they were practically insoluble in acetone at 25°C (0.015 mg/mL). HC-loaded ONTs were prepared by solvent evaporation using acetone. A sample with a 3/7 weight ratio of HC/ONT was analyzed by powder X-ray diffraction, which confirmed the presence of a halo pattern and the absence of any crystalline HC peak. HC peak broadening, observed by solid-state (13)C-NMR measurements of the evaporated sample, indicated the absence of HC crystals. These results indicated that HC was successfully encapsulated in ONT as an amorphous state. Improvements of the HC dissolution rate were clearly observed in aqueous media at both pH 1.2 and 6.8, probably due to HC amorphization in the ONTs. Phenytoin, another poorly water-soluble drug, also showed significant dissolution improvement upon ONT encapsulation. Therefore, ONTs can serve as an alternative pharmaceutical excipient to enhance the bioavailability of poorly water-soluble drugs.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan. Electronic address: moribe@faculty.chiba-u.jp.
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Moribe
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Makishima
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Kenjirou
authors.initials: K
authors.lastname: Higashi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Nan
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Manufacturing Pharmacy, Faculty of Pharmacy, Mahidol University, 447 Sri Ayudhya Road, Ratchatewi, Bangkok 10400, Thailand.
authors.forename: Waree
authors.initials: W
authors.lastname: Limwikrant
authors.affiliation: Nanosystem Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba Central 5, Higashi 1-1-1, Tsukuba, Ibaraki 305-8565, Japan.
authors.forename: Wuxiao
authors.initials: W
authors.lastname: Ding
authors.affiliation: Nanosystem Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba Central 5, Higashi 1-1-1, Tsukuba, Ibaraki 305-8565, Japan.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Masuda
authors.affiliation: Nanosystem Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba Central 5, Higashi 1-1-1, Tsukuba, Ibaraki 305-8565, Japan.
authors.forename: Toshimi
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D002626:Chemistry, Pharmaceutical; D018360:Crystallography, X-Ray; D005079:Excipients / Q000737:chemistry*; D006854:Hydrocortisone / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D043942:Nanotubes; D011108:Polymers / Q000737:chemistry*; D033362:Powder Diffraction; D066244:Proton Magnetic Resonance Spectroscopy; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods*; D014867:Water / Q000737:chemistry*
chemical_list: D005079:Excipients; D011108:Polymers; D012997:Solvents; D014867:Water; D006854:Hydrocortisone
keywords: Amorphous; Dissolution rate enhancement; Drug encapsulation; Hydrocortisone; Organic nanotube; Phenytoin