<abstract xmlns="http://www.w3.org/1999/xhtml">Simvastatin is poorly bioavailable because it is practically insoluble in water and shows dissolution rate-limited absorption. Solubilizing effects of several <italic>β</italic>-cyclodextrin (<italic>β</italic>CD) derivatives such as HP<italic>β</italic>CD, SBE<italic>β</italic>CD and DM<italic>β</italic>CD on simvastatin in aqueous solution were investigated using the phase solubility technique. The solubility diagram of simvastatin with each <italic>β</italic>CD derivative could be classified as AL-type, indicating soluble complex formation of 1:1 stoichiometry. Among the above <italic>β</italic>CD derivatives DM<italic>β</italic>CD was found to be the ideal complexing agent for improving drug solubility. The simvastatin complex with DM<italic>β</italic>CD was prepared using the co-evaporation method and was then characterized by differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR) and <italic>in vitro</italic> dissolution. Dissolution and pharmacokinetic studies indicated that the simvastatin/DM<italic>β</italic>CD complex exhibited an increased dissolution rate, rapid absorption, and improved bioavailability in rats compared to free drug. Maximum plasma concentration (<italic>c</italic>max) and the time to reach it (<italic>t</italic>max) were 21.86 μg mL−1 and 1.4 h for the drug complex, 8.25 μg mL−1 and 3.0 h for free drug, respectively. Main pharmacokinetic parameters such as <italic>t</italic>max, <italic>c</italic>max were significantly different (<italic>p &lt;</italic> 0.01) between the simvastatin complex and free drug. Bioavailability of the simvastatin complex relative to free drug was up to 167.0 %.</abstract>

Simvastatin is poorly bioavailable because it is practically insoluble in water and shows dissolution rate-limited absorption. Solubilizing effects of several β-cyclodextrin (βCD) derivatives such as HPβCD, SBEβCD and DMβCD on simvastatin in aqueous solution were investigated using the phase solubility technique. The solubility diagram of simvastatin with each βCD derivative could be classified as AL-type, indicating soluble complex formation of 1:1 stoichiometry. Among the above βCD derivatives DMβCD was found to be the ideal complexing agent for improving drug solubility. The simvastatin complex with DMβCD was prepared using the co-evaporation method and was then characterized by differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR) and in vitro dissolution. Dissolution and pharmacokinetic studies indicated that the simvastatin/DMβCD complex exhibited an increased dissolution rate, rapid absorption, and improved bioavailability in rats compared to free drug. Maximum plasma concentration (cmax) and the time to reach it (tmax) were 21.86 μg mL−1 and 1.4 h for the drug complex, 8.25 μg mL−1 and 3.0 h for free drug, respectively. Main pharmacokinetic parameters such as tmax, cmax were significantly different (p < 0.01) between the simvastatin complex and free drug. Bioavailability of the simvastatin complex relative to free drug was up to 167.0 %.

Preparation and characterization of simvastatin/DM<italic>β</italic>CD complex and its pharmacokinetics in rats

Department of Pharmaceutics, Affiliated Hospital

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Preparation and characterization of simvastatin/DMCD complex and its pharmacokinetics in rats

Simvastatin is poorly bioavailable because it is practically insoluble in water and shows dissolution rate-limited absorption. Solubilizing effects of several...

Preparation and characterization of simvastatin/DMβCD complex and its pharmacokinetics in rats

Publié en ligne: 26 avr. 2018

Pages: 145 - 157

Accepté: 15 janv. 2018

DOI: https://doi.org/10.2478/acph-2018-0016

Mots clés
simvastatin, DMCD, complex, solubility, dissolution rate, pharmacokinetics

© 2018 Fugen Gu et al., published by De Gruyter Open

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Preparation and characterization of simvastatin/DMβCD complex and its pharmacokinetics in rats

Publié en ligne: 26 avr. 2018

Pages: 145 - 157

Accepté: 15 janv. 2018

DOI: https://doi.org/10.2478/acph-2018-0016

Mots cléssimvastatin, DMCD, complex, solubility, dissolution rate, pharmacokinetics

© 2018 Fugen Gu et al., published by De Gruyter Open

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Mots clés
simvastatin, DMCD, complex, solubility, dissolution rate, pharmacokinetics