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Complexation of Manidipine with Cyclodextrins and their Derivatives

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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 μg/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-βCD 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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Authors and Affiliations

  1. Cyclolab, Cyclodextrin Research and Development Laboratory Ltd., H-1525, Budapest, P.O. Box 435, Hungary

    Katalin Csabai, Maria Vikmon & József Szejtli

  2. Chemical and Biopharmaceutical Department, Chiesi Farmaceutici S.p.A., Via Palermo 26A, I-43100, Parma, Italy

    Enrico Redenti, Gianluigi Poli & Paolo Ventura

Authors
  1. Katalin Csabai
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  2. Maria Vikmon
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  3. József Szejtli
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  4. Enrico Redenti
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  5. Gianluigi Poli
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  6. Paolo Ventura
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Csabai, K., Vikmon, M., Szejtli, J. et al. Complexation of Manidipine with Cyclodextrins and their Derivatives. Journal of Inclusion Phenomena 31, 169–178 (1998). https://doi.org/10.1023/A:1007959417684

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  • DOI: https://doi.org/10.1023/A:1007959417684

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