Preparation and characterization of simvastatin/DMβCD 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 β-cyclodextrin (βCD) derivatives such as HPβCD, SBEβCD and DMβCD on simvastatin in aqueous solution were investigated using the phase solubil...
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| Format: | Article |
| Language: | English |
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Sciendo
2018-06-01
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| Series: | Acta Pharmaceutica |
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| Online Access: | https://doi.org/10.2478/acph-2018-0016 |
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| author | Gu Fugen Ning Jia Fan Huimin Wu Chunzhi Wang Yi |
| author_facet | Gu Fugen Ning Jia Fan Huimin Wu Chunzhi Wang Yi |
| author_sort | Gu Fugen |
| collection | DOAJ |
| description | 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 %. |
| format | Article |
| id | doaj-art-0229584dadca49ecb009f05862d607d5 |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2018-06-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Pharmaceutica |
| spelling | doaj-art-0229584dadca49ecb009f05862d607d52025-02-02T00:31:54ZengSciendoActa Pharmaceutica1846-95582018-06-0168214515710.2478/acph-2018-0016acph-2018-0016Preparation and characterization of simvastatin/DMβCD complex and its pharmacokinetics in ratsGu Fugen0Ning Jia1Fan Huimin2Wu Chunzhi3Wang Yi4Department of Pharmaceutics, Affiliated Hospital, Inner Mongolia Medical University, Hohhot010050ChinaSchool of Pharmacy, Inner Mongolia Medical University, Hohhot010110ChinaSchool of Pharmacy, Inner Mongolia Medical University, Hohhot010110ChinaDepartment of Pharmaceutics, Affiliated Hospital, Inner Mongolia Medical University, Hohhot010050ChinaDepartment of Pharmaceutics, Affiliated Hospital, Inner Mongolia Medical University, Hohhot010050ChinaSimvastatin 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 %.https://doi.org/10.2478/acph-2018-0016simvastatindmβcdcomplexsolubilitydissolution ratepharmacokinetics |
| spellingShingle | Gu Fugen Ning Jia Fan Huimin Wu Chunzhi Wang Yi Preparation and characterization of simvastatin/DMβCD complex and its pharmacokinetics in rats Acta Pharmaceutica simvastatin dmβcd complex solubility dissolution rate pharmacokinetics |
| title | Preparation and characterization of simvastatin/DMβCD complex and its pharmacokinetics in rats |
| title_full | Preparation and characterization of simvastatin/DMβCD complex and its pharmacokinetics in rats |
| title_fullStr | Preparation and characterization of simvastatin/DMβCD complex and its pharmacokinetics in rats |
| title_full_unstemmed | Preparation and characterization of simvastatin/DMβCD complex and its pharmacokinetics in rats |
| title_short | Preparation and characterization of simvastatin/DMβCD complex and its pharmacokinetics in rats |
| title_sort | preparation and characterization of simvastatin dmβcd complex and its pharmacokinetics in rats |
| topic | simvastatin dmβcd complex solubility dissolution rate pharmacokinetics |
| url | https://doi.org/10.2478/acph-2018-0016 |
| work_keys_str_mv | AT gufugen preparationandcharacterizationofsimvastatindmbcdcomplexanditspharmacokineticsinrats AT ningjia preparationandcharacterizationofsimvastatindmbcdcomplexanditspharmacokineticsinrats AT fanhuimin preparationandcharacterizationofsimvastatindmbcdcomplexanditspharmacokineticsinrats AT wuchunzhi preparationandcharacterizationofsimvastatindmbcdcomplexanditspharmacokineticsinrats AT wangyi preparationandcharacterizationofsimvastatindmbcdcomplexanditspharmacokineticsinrats |