Complexation of Manidipine with Cyclodextrins and their Derivatives |
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Authors: | Katalin Csabai Maria Vikmon József Szejtli Enrico Redenti Gianluigi Poli Paolo Ventura |
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Affiliation: | (1) Cyclolab, Cyclodextrin Research and Development Laboratory Ltd., H-1525 Budapest, P.O. Box 435, Hungary;(2) Chemical and Biopharmaceutical Department, Chiesi Farmaceutici S.p.A., Via Palermo 26A, I-43100 Parma, Italy |
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Abstract: | Manidipine (MDP,(±)-2-[-(diphenylmethyl)-1-piperazinyl]ethylmethyl-1,4-dihydro-2,6-dimethyl-4(m-nitrophenyl)-3,5-pyridinedicarboxylate methyl-ester) is a poorlysoluble (<1 g/mL) long acting antihypertensive drug. Salt formingwith citric or tartaric acid results in a 400 to 600 fold solubilityenhancement, respectively, which can be further increased by an order ofmagnitude with cyclodextrins. Dimethyl-CD alone results in a more than8000 fold solubility enhancement. Besides the strongly enhanced solubility1HNMR spectroscopy also proves the inclusion-type interactionbetween Manidipine and cyclodextrins. From the attained 5-8 mg/mL solubilityof the drug in water an improved bioavailability and pharmacokinetics isexpected. |
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Keywords: | manidipine cyclodextrin multicomponent complex citric acid tartaric acid hydroxy acids |
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