Effect of solubilizing strategies on oral absorption of felodipine

LI Qiang; WANG Wendie; JIA Yue; ZHENG Yuzhao; ZHOU Jianping; YIN Tingjie

doi:10.11665/j.issn.1000-5048.20210208

Journal of China Pharmaceutical University > 2021 > 52(2): 195-202. > DOI: 10.11665/j.issn.1000-5048.20210208

LI Qiang, WANG Wendie, JIA Yue, ZHENG Yuzhao, ZHOU Jianping, YIN Tingjie. Effect of solubilizing strategies on oral absorption of felodipine[J]. Journal of China Pharmaceutical University, 2021, 52(2): 195-202. DOI: 10.11665/j.issn.1000-5048.20210208

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Effect of solubilizing strategies on oral absorption of felodipine

Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China

Funds: This study was supported by the National Science and Technology Major Project of China (No. 2017ZX09101001-004-002)

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Received Date: December 03, 2020
Revised Date: March 23, 2021

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Abstract

As a typical BCS Ⅱ drug, felodipine exhibits low solubility and high permeability. We herein investigated the effects of different solubilization strategies on the oral absorption of felodipine. Firstly felodipine tablets based on 200 μm, 150 μm and 25 μm particle size of bulk drug were prepared. Meanwhile, felodipine solid dispersion and felodipine nanosuspension with average particle size of (168.90 ± 6.22) nm, PDI of 0.11 ± 0.06 were prepared. The absorption rate, apparent permeability coefficient (P_app), absorption quality in duodenum, jejunum, ileum and colon of rats and in vivo pharmacokinetics of the above different felodipine preparations were investigated. The results of rat single-pass intestinal perfusion showed that the absorption of felodipine preparations in duodenum, jejunum and ileum was better than in colon. Felodipine had a wide absorption window in the small intestine, with the best absorption site in the small intestine. P_app of different felodipine preparations was greater than 2.0 × 10^-5cm/s. Thus, the low solubility was the main factor limiting the absorption. In vivo pharmacokinetic experiments demonstrated the solubilization strategies significantly improved the bioavailability. The bioavailabilities of felodipine tablets with particle sizes of 150 and 25 μm, as well as nanosuspension, and solid dispersion were 138.75%, 173.01%, 208.65% and 314.53% that of the tablets with particle size of 200 μm, respectively. Solubilization strategies can significantly improve the gastrointestinal absorption rate and absorption quality of felodipine, and thus improve its bioavailability, which provides some reference for the research on the improvement of oral absorption of BCS II drugs.
- felodipine,
- solubilizing,
- promote absorption,
- nanosuspension,
- solid dispersion

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