Improved oral bioavailability of poorly water-soluble glimepiride by utilizing microemulsion technique
Haiying Li,1 Tingting Pan,1 Ying Cui,1 Xiaxia Li,1 Jiefang Gao,1 Wenzhi Yang,1 Shigang Shen2 1Key Laboratory of Pharmaceutical Quality Control of Hebei Province, College of Pharmacy, 2Key Laboratory of Analytical Science and Technology of Hebei Province, College of Chemistry and Environmental Scien...
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2016-08-01
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doaj-0f3ad52f0f954789819e76f627c57d572020-11-25T00:03:22ZengDove Medical PressInternational Journal of Nanomedicine1178-20132016-08-012016default3777378828279Improved oral bioavailability of poorly water-soluble glimepiride by utilizing microemulsion techniqueLi HYPan TTCui YLi XXGao JFYang WZShen SGHaiying Li,1 Tingting Pan,1 Ying Cui,1 Xiaxia Li,1 Jiefang Gao,1 Wenzhi Yang,1 Shigang Shen2 1Key Laboratory of Pharmaceutical Quality Control of Hebei Province, College of Pharmacy, 2Key Laboratory of Analytical Science and Technology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding, People’s Republic of China Abstract: The objective of this work was to prepare an oil/water glimepiride (GM) microemulsion (ME) for oral administration to improve its solubility and enhance its bioavailability. Based on a solubility study, pseudoternary phase diagrams, and Box–Behnken design, the oil/water GMME formulation was optimized and prepared. GMME was characterized by dynamic laser light scattering, zeta potential, transmission electron microscopy, and viscosity. The in vitro drug release, storage stability, pharmacodynamics, and pharmacokinetics of GMME were investigated. The optimized GMME was composed of Capryol 90 (oil), ­Cremophor RH40 (surfactant), and Transcutol (cosurfactant), and increased GM solubility up to 544.6±4.91 µg/mL. The GMME was spherical in shape. The particle size and its polydispersity index were 38.9±17.46 nm and 0.266±0.057, respectively. Meanwhile, the GMME was physicochemically stable at 4°C for at least 3 months. The short-term efficacy in diabetic mice provided the proof that blood glucose had a consistent and significant reduction at a dose of 375 µg/kg whether via IP injection or IG administration of GMME. Compared with the glimepiride suspensions or glimepiride-meglumine complex solution, the pharmacokinetics of GMME in Wistar rats via IG administration exhibited higher plasma drug concentration, larger area under the curve, and more enhanced oral bioavailability. There was a good correlation of GMME between the in vitro release values and the in vivo oral absorption. ME could be an effective oral drug delivery system to improve bioavailability of GM. Keywords: glimepiride, microemulsion, solubility, pharmacodynamics, pharmacokineticshttps://www.dovepress.com/improved-oral-bioavailability-of-poorly-water-soluble-glimepiride-by-u-peer-reviewed-article-IJNglimepiridemicroemulsionsolubilitypharmacodynamicspharmacokinetics |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Li HY Pan TT Cui Y Li XX Gao JF Yang WZ Shen SG |
spellingShingle |
Li HY Pan TT Cui Y Li XX Gao JF Yang WZ Shen SG Improved oral bioavailability of poorly water-soluble glimepiride by utilizing microemulsion technique International Journal of Nanomedicine glimepiride microemulsion solubility pharmacodynamics pharmacokinetics |
author_facet |
Li HY Pan TT Cui Y Li XX Gao JF Yang WZ Shen SG |
author_sort |
Li HY |
title |
Improved oral bioavailability of poorly water-soluble glimepiride by utilizing microemulsion technique |
title_short |
Improved oral bioavailability of poorly water-soluble glimepiride by utilizing microemulsion technique |
title_full |
Improved oral bioavailability of poorly water-soluble glimepiride by utilizing microemulsion technique |
title_fullStr |
Improved oral bioavailability of poorly water-soluble glimepiride by utilizing microemulsion technique |
title_full_unstemmed |
Improved oral bioavailability of poorly water-soluble glimepiride by utilizing microemulsion technique |
title_sort |
improved oral bioavailability of poorly water-soluble glimepiride by utilizing microemulsion technique |
publisher |
Dove Medical Press |
series |
International Journal of Nanomedicine |
issn |
1178-2013 |
publishDate |
2016-08-01 |
description |
Haiying Li,1 Tingting Pan,1 Ying Cui,1 Xiaxia Li,1 Jiefang Gao,1 Wenzhi Yang,1 Shigang Shen2 1Key Laboratory of Pharmaceutical Quality Control of Hebei Province, College of Pharmacy, 2Key Laboratory of Analytical Science and Technology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding, People’s Republic of China Abstract: The objective of this work was to prepare an oil/water glimepiride (GM) microemulsion (ME) for oral administration to improve its solubility and enhance its bioavailability. Based on a solubility study, pseudoternary phase diagrams, and Box–Behnken design, the oil/water GMME formulation was optimized and prepared. GMME was characterized by dynamic laser light scattering, zeta potential, transmission electron microscopy, and viscosity. The in vitro drug release, storage stability, pharmacodynamics, and pharmacokinetics of GMME were investigated. The optimized GMME was composed of Capryol 90 (oil), ­Cremophor RH40 (surfactant), and Transcutol (cosurfactant), and increased GM solubility up to 544.6±4.91 µg/mL. The GMME was spherical in shape. The particle size and its polydispersity index were 38.9±17.46 nm and 0.266±0.057, respectively. Meanwhile, the GMME was physicochemically stable at 4°C for at least 3 months. The short-term efficacy in diabetic mice provided the proof that blood glucose had a consistent and significant reduction at a dose of 375 µg/kg whether via IP injection or IG administration of GMME. Compared with the glimepiride suspensions or glimepiride-meglumine complex solution, the pharmacokinetics of GMME in Wistar rats via IG administration exhibited higher plasma drug concentration, larger area under the curve, and more enhanced oral bioavailability. There was a good correlation of GMME between the in vitro release values and the in vivo oral absorption. ME could be an effective oral drug delivery system to improve bioavailability of GM. Keywords: glimepiride, microemulsion, solubility, pharmacodynamics, pharmacokinetics |
topic |
glimepiride microemulsion solubility pharmacodynamics pharmacokinetics |
url |
https://www.dovepress.com/improved-oral-bioavailability-of-poorly-water-soluble-glimepiride-by-u-peer-reviewed-article-IJN |
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