Journal of Thermal Analysis and Calorimetry
Volume/Issue:
Volume 77: Issue 2
Mechanism for the inhibition of the acid degradation of ampicillin by 2-hydroxypropyl- β -cyclodextrin
Authors:
H. Aki Fukuoka University Faculty of Pharmaceutical Sciences 8-19-1 Nanakuma Jonan-ku, Fukuoka 814-0180 Japan 8-19-1 Nanakuma Jonan-ku, Fukuoka 814-0180 Japan

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T. Niiya Fukuoka University Faculty of Pharmaceutical Sciences 8-19-1 Nanakuma Jonan-ku, Fukuoka 814-0180 Japan 8-19-1 Nanakuma Jonan-ku, Fukuoka 814-0180 Japan

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Y. Iwase Fukuoka University Faculty of Pharmaceutical Sciences 8-19-1 Nanakuma Jonan-ku, Fukuoka 814-0180 Japan 8-19-1 Nanakuma Jonan-ku, Fukuoka 814-0180 Japan

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M. Goto Fukuoka University Faculty of Pharmaceutical Sciences 8-19-1 Nanakuma Jonan-ku, Fukuoka 814-0180 Japan 8-19-1 Nanakuma Jonan-ku, Fukuoka 814-0180 Japan

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T. Kimura Kinki University Faculty of Science and Technology Kowakae 3-4-1, Higashi-Osaka 3-4-1 Osaka 577-8502 Japan Kowakae 3-4-1, Higashi-Osaka 3-4-1 Osaka 577-8502 Japan

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Pages:
423–435
Online Publication Date:
14 Jan 2005
Publication Date:
01 Aug 2004
Article Category:
Research Article
DOI:
https://doi.org/10.1023/b:jtan.0000038983.01236.42
Keywords:
microcalorimetry; molecular dynamics simulation; amoxicillin; 2-hydroxypropyl- ? -cyclodextrine; inclusion complex
Restricted access

Abstract  

The formation of inclusion complexes between amoxicillin (AMPC) and 2-hydroxypropyl-β-cyclodextrin (HPCD) was investigated by isothermal microcalorimetry and molecular dynamics simulation to evaluate the inhibitory effects on the degradation of AMPC in aqueous solutions at various pH. The process depended significantly on the ionic species of AMPC in the solution. In a strong acid solution, cationic AMPC and HPCD formed two different types of inclusion complexes with a 1:1 stoichiometry: the first-type had a high association constant K1 of 4.0-8.0103 M-1 and included the penam ring of AMPC in the HPCD cavity (Mode I), while the second-type with a K2 of 1.0103 M-1 contained the phenyl group of AMPC (Mode II). Furthermore, a complex with a 1:2 (AMPC:HPCD) stoichiometry was realized in a two-step reaction and was characterized by a smaller K1:2of 4.0102 M-1 and larger negative enthalpy and entropy changes than the complexes with a 1:1 stoichiometry. Since the β-lactam ring of AMPC could be protected by inclusion with HPCD in the 1:2 complex and Mode I of 1:1 complexes, the degradation of AMPC in the presence of HPCD was approximately four times slower than in its absence at pH 1.2 and 37C. In weak acid and neutral solutions, zwitterionic AMPC and HPCD formed only one type of inclusion complex with a 1:1 stoichiometry, where the phenyl group was included (Mode II). AMPC was very stable in these solutions (t1/2=226 h at pH=6.0) and there is little significant difference in the degradation rate between complexed AMPC and uncomplexed AMPC. Thus, the results indicated that the inclusion complex of AMPC with HPCD, effectively increasing the stability of AMPC in a strong acidic solution like that the stomach, would be useful for eradicating Helicobacter pylori infection and as a drug delivery system.

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Cover Journal of Thermal Analysis and Calorimetry
Journal of Thermal Analysis and Calorimetry
Print ISSN:
1388-6150
Online ISSN:
1572-8943

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Journal of Thermal Analysis and Calorimetry
Language English
Size A4
Year of
Foundation		 1969
Volumes
per Year		 1
Issues
per Year		 24
Founder Akadémiai Kiadó
Founder's
Address		 H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Publisher Akadémiai Kiadó
Springer Nature Switzerland AG
Publisher's
Address		 H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
CH-6330 Cham, Switzerland Gewerbestrasse 11.
Responsible
Publisher		 Chief Executive Officer, Akadémiai Kiadó
ISSN 1388-6150 (Print)
ISSN 1588-2926 (Online)

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