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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
Citation: 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
shu

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
    Graphical Abstract
    • 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 (Papp), 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. Papp of different felodipine preparations was greater than 2.0 × 10-5 cm/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.
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    • References (14)
  • [1]
    . Drug Eval Res（药物评价研究），2019，42（5）：1014-1019.
    [2]
    Lüscher TF，Cosentino F. The classification of calcium antagonists and their selection in the treatment of hypertension. areappraisal［J］. Drugs，1998，55（4）：509-517.
    [3]
    Zhou Z，Dunn C，Khadra I，et al. Influence of physiological gastrointestinal surfactant ratio on the equilibrium solubility of BCS Class II drugs investigated using a four component mixture design［J］. Mol Pharm，2017，14（12）：4132-4144.
    [4]
    ?těpánková M，Krasulová K，Do?i?áková A，et al. Optical isomers of dihydropyridine calcium channel blockers display enantiospecific effects on the expression and enzyme activities of human xenobiotics-metabolizing cytochromes P450［J］. Toxicol Lett，2016，262：173-186.
    [5]
    Jing BY，Wang ZY，Yang R，et al. Enhanced oral bioavailability of felodipine by novel solid self-microemulsifying tablets［J］. Drug Dev Ind Pharm，2016，42（3）：506-512.
    [6]
    Zhang CG，Yu ZY，Yu CC，et al. Research progress of gastroretentive drug delivery system and its application in traditional Chinese medicine［J］. Chin J Mod Appl Pharm（中国现代应用药学），2020，37（7）：877-885.
    [7]
    Jing BY，Wang ZY，Li Y，et al. Preparation and in vitro evaluation of felodipinesolid dispersions［J］. J Shenyang Pharm Univ（沈阳药科大学学报），2010，27（3）：185-190.
    [8]
    Mori D，Makwana J，Parmar R，et al. Formulation， evaluation and optimization of the felodipine nanosuspension to be used for direct compression to tablet for in vitro dissolution enhancement［J］. Pak J Pharm Sci，2016，29（6）：1927-1936.
    [9]
    Yang H，Zhai B，Fan Y，et al. Intestinal absorption mechanisms of araloside a in situ single-pass intestinal perfusion and in vitro caco-2 cell model［J］. Biomed Pharmacother. 2018，106：1563-1569.
    [10]
    Zawaneh AH，Khalil NN，Ibrahim SA，et al. Micelle-enhanced direct spectrofluorimetric method for the determination of linifanib： application to stability studies［J］. Luminescence，2017，32（7）：1162-1168.
    [11]
    He CH，Zhang ZH，Wang S，et al. Study on intestinal absorption kinetics of apigenin in rats［J］. Chin J Chin Mater Med（中国中药杂志），2013，38（9）：1416-1420.
    [12]
    Luo YF，Ren LX，Li XH，et al. Summary of research methods for drug intestinal absorption［J］. Drug Eval Res（药物评价研究），2017，40（5）：706-710.
    [13]
    Zhou YJ，Qin DP，Wang YD，et al. Amelioration of tripterygium wilfordii polycoride on TNBS/ethanolinduced ulcerative colitis via inhibiting lipid peroxidation and its downstream inflammatory meditors［J］. Chin Herb Med（中草药 英文版），2017，9（4）：344-352.
    [14]
    Over B，Matsson P，Tyrchan C，et al. Structural and conformational determinants of macrocycle cell permeability［J］. Nat Chem Biol，2016，12（12）：1065-1074.
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