Characterization and in vivo evaluation of lacidipine inclusion complexes with β-cyclodextrin and its derivatives

T. Darekar, K. S. Aithal, R. Shirodkar, L. Kumar, Z. Attari, S. Lewis

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The objective of the study was to explore the possible formation of the inclusion complex of lacidipine (LCDP), a class II drug under biopharmaceutics classification system (BCS) with beta-cyclodextrin (β-CD) and modified β-CDs: hydroxy propyl- beta-cyclodextrin (HP-β-CD) and sulfobutyl ether-beta-cyclodextrin (SBE-β-CD) in order to enhance the solubility and the dissolution rate of the drug with an intention to improve its bioavailability. The stability constants found using phase solubility studies showed that SBE-β-CD formed the most stable inclusion complex with the drug (K = 348 ± 4 M-1) compared to the other cyclodextrins (CDs). The thermal analysis confirmed this finding. IR spectral analysis indicated the involvement of the hydroxyl function of CDs with the COOH of the drug. H1 NMR and 13C NMR spectral analysis indicated that the aromatic ring of drug included deeply in the CD cavity leaving the side chain protruding outside the CD cage and hydrogen bonds are formed which stabilizes the complex formation. The dissolution of the drug was improved on complexation with SBE-β-CD more effectively compared to the other CDs. The in vivo pharmacokinetic study of the complexes in Wistar rats showed an increase in AUC value by 1.5-2 times in case of (HP-β-CD) and SBE-β-CD compared to the plain drug and maximum with SBE-β-CD complex (Cmax = 242 ± 150 ng/ml, AUC = 1506.95 ± 0.505 ng/ml h).

Original languageEnglish
Pages (from-to)225-235
Number of pages11
JournalJournal of Inclusion Phenomena and Macrocyclic Chemistry
Volume84
Issue number3-4
DOIs
Publication statusPublished - 01-04-2016

Fingerprint

cyclodextrins
beta-cyclodextrin
Cyclodextrins
drugs
chemical derivatives
inclusions
ethers
evaluation
Pharmaceutical Preparations
Solubility
Area Under Curve
Spectrum analysis
spectrum analysis
Biopharmaceutics
dissolving
Dissolution
spectral analysis
solubility
Nuclear magnetic resonance
bioavailability

All Science Journal Classification (ASJC) codes

  • Food Science
  • Chemistry(all)
  • Condensed Matter Physics

Cite this

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abstract = "The objective of the study was to explore the possible formation of the inclusion complex of lacidipine (LCDP), a class II drug under biopharmaceutics classification system (BCS) with beta-cyclodextrin (β-CD) and modified β-CDs: hydroxy propyl- beta-cyclodextrin (HP-β-CD) and sulfobutyl ether-beta-cyclodextrin (SBE-β-CD) in order to enhance the solubility and the dissolution rate of the drug with an intention to improve its bioavailability. The stability constants found using phase solubility studies showed that SBE-β-CD formed the most stable inclusion complex with the drug (K = 348 ± 4 M-1) compared to the other cyclodextrins (CDs). The thermal analysis confirmed this finding. IR spectral analysis indicated the involvement of the hydroxyl function of CDs with the COOH of the drug. H1 NMR and 13C NMR spectral analysis indicated that the aromatic ring of drug included deeply in the CD cavity leaving the side chain protruding outside the CD cage and hydrogen bonds are formed which stabilizes the complex formation. The dissolution of the drug was improved on complexation with SBE-β-CD more effectively compared to the other CDs. The in vivo pharmacokinetic study of the complexes in Wistar rats showed an increase in AUC value by 1.5-2 times in case of (HP-β-CD) and SBE-β-CD compared to the plain drug and maximum with SBE-β-CD complex (Cmax = 242 ± 150 ng/ml, AUC = 1506.95 ± 0.505 ng/ml h).",
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Characterization and in vivo evaluation of lacidipine inclusion complexes with β-cyclodextrin and its derivatives. / Darekar, T.; Aithal, K. S.; Shirodkar, R.; Kumar, L.; Attari, Z.; Lewis, S.

In: Journal of Inclusion Phenomena and Macrocyclic Chemistry, Vol. 84, No. 3-4, 01.04.2016, p. 225-235.

Research output: Contribution to journalArticle

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T1 - Characterization and in vivo evaluation of lacidipine inclusion complexes with β-cyclodextrin and its derivatives

AU - Darekar, T.

AU - Aithal, K. S.

AU - Shirodkar, R.

AU - Kumar, L.

AU - Attari, Z.

AU - Lewis, S.

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AB - The objective of the study was to explore the possible formation of the inclusion complex of lacidipine (LCDP), a class II drug under biopharmaceutics classification system (BCS) with beta-cyclodextrin (β-CD) and modified β-CDs: hydroxy propyl- beta-cyclodextrin (HP-β-CD) and sulfobutyl ether-beta-cyclodextrin (SBE-β-CD) in order to enhance the solubility and the dissolution rate of the drug with an intention to improve its bioavailability. The stability constants found using phase solubility studies showed that SBE-β-CD formed the most stable inclusion complex with the drug (K = 348 ± 4 M-1) compared to the other cyclodextrins (CDs). The thermal analysis confirmed this finding. IR spectral analysis indicated the involvement of the hydroxyl function of CDs with the COOH of the drug. H1 NMR and 13C NMR spectral analysis indicated that the aromatic ring of drug included deeply in the CD cavity leaving the side chain protruding outside the CD cage and hydrogen bonds are formed which stabilizes the complex formation. The dissolution of the drug was improved on complexation with SBE-β-CD more effectively compared to the other CDs. The in vivo pharmacokinetic study of the complexes in Wistar rats showed an increase in AUC value by 1.5-2 times in case of (HP-β-CD) and SBE-β-CD compared to the plain drug and maximum with SBE-β-CD complex (Cmax = 242 ± 150 ng/ml, AUC = 1506.95 ± 0.505 ng/ml h).

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JO - Journal of Inclusion Phenomena and Macrocyclic Chemistry

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SN - 1388-3127

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