Common solubilizers to estimate the Caco-2 transport of poorly water-soluble drugs

Takahashi, Yutaka; Kondo, Hiromu; Tatsuo, Yasuda; Watanabe, Takashi; Kobayashi, Shinichiro; Yokohama, Shigeharu

doi:10.1016/s0378-5173(02)00347-2

Cited by 78 publications

(52 citation statements)

References 17 publications

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“…Furthermore, most buffers used for in vitro drug delivery studies with tissue culture are very hydrophilic and contain counter ions, which undermines the solubility of poorly watersoluble compounds (Dollo et al, 1999). There is a need from the biopharmaceutical standpoint to increase the aqueous solubility of poorly-soluble non-ionizable drugs in order to circumvent low and highly variable absorption generally seen with such compounds (Takahashi et al, 2002). Solubilizers such as polyethylene glycol 400 (PEG 400), N-Dimethylacetamide (DMA), Cremophor (Yamashita et al, 2000;Ginski et al, 2000;Saha & Kou, 2000;Takahashi et al, 2002;Watanabe et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…There is a need from the biopharmaceutical standpoint to increase the aqueous solubility of poorly-soluble non-ionizable drugs in order to circumvent low and highly variable absorption generally seen with such compounds (Takahashi et al, 2002). Solubilizers such as polyethylene glycol 400 (PEG 400), N-Dimethylacetamide (DMA), Cremophor (Yamashita et al, 2000;Ginski et al, 2000;Saha & Kou, 2000;Takahashi et al, 2002;Watanabe et al, 2005). In order to avoid potential detrimental effects of solubilizers on epithelial cells, most researchers use arbitrarily chosen low concentrations (usually less than 1%) for transport and metabolism studies.…”

Section: Introductionmentioning

confidence: 99%

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Water-soluble organic solubilizers for in vitro drug delivery studies with respiratory epithelial cells: Selection based on various toxicity indicators

et al. 2010

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Water-soluble organic solubilizers for in vitro drug delivery studies with respiratory epithelial cells: Selection based on various toxicity indicators

et al. 2010

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“…[23][24][25] Solubility study The solubility of FVS in different vehicles was determined by adding 40 mg of FVS into 1 mL of each vehicle in the centrifugal tube, followed by mixing in a shaker incubator at 37°C for 72 hours. The mixture was then centrifuged at 10,000 rpm for 10 minutes to remove the excess FVS.…”

Section: Optimization Of Blank Microemulsion Prescriptionmentioning

confidence: 99%

Enhanced oral bioavailability of a sterol-loaded microemulsion formulation of Flammulina velutipes, a potential antitumor drug

Yi¹,

Zhong²,

Tong³

et al. 2012

IJN

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Purpose:To investigate the growth inhibition activity of Flammulina velutipes sterol (FVS) against certain human cancer cell lines (gastric SGC and colon LoVo) and to evaluate the optimum microemulsion prescription, as well as the pharmacokinetics of encapsulated FVS. Methods: Molecules present in the FVS isolate were identified by gas chromatography/mass spectrometry analysis. The cell viability of FVS was assessed with methyl thiazolyl tetrazolium (MTT) bioassay. Based on the solubility study, phase diagram and stability tests, the optimum prescription of F. velutipes sterol microemulsions (FVSMs) were determined, followed by FVSMs characterization, and its in vivo pharmacokinetic study in rats. ). The optimal FVSMs prescription consisted of 3.0% medium chain triglycerides, 5.0% ethanol, 21.0% Cremophor EL and 71.0% water (w/w) with associated solubility of FVS being 0.680 mg ⋅ mL −1 as compared to free FVS (0.67 µg ⋅ mL −1 ). The relative oral bioavailability (area-under-the-curve values of ergosterol and 22,23-dihydroergosterol showed a 2.56-fold and 4.50-fold increase, respectively) of FVSMs (mean diameter ∼ 22.9 nm) as against free FVS were greatly enhanced. Our laboratory has been able to screen out lipid soluble sterols with an antitumor effect from F. velutipes by lipidraft chromatography, which was found to be linked to the tyrosine kinase receptor (data not published). In this study, our laboratory was interested in performing a preliminary investigation of the anticancer potential and bioavailability of F. velutipes sterol (FVS) as an in-depth contribution to the research of F. velutipes. FVS is a white powder, which can easily dissolve in ether, chloroform, hot ethanol, and other organic solvents, but barely dissolves in water. As a result, it is necessary to find a method to improve the solubility and oral bioavailability of this sterol. Dovepress 5067 O R I G I N A L R E S E A R C HMicroemulsions are thermodynamically stable nanometer systems with characteristics of easy preparation, small droplet size, low viscosity, and strong solubilization effect. 12It is formed spontaneously by water, oil, surfactant and cosurfactant. 13,14 According to the structure of a microemulsion, it can be divided into water-in-oil (w/o), oil-in-water (o/w) and bicontinuous microemulsion. 15 As a drug carrier, a microemulsion can increase the solubility and oral bioavailability of poorly soluble drugs, ameliorate the localization, improve systemic delivery of the drug, and possess the ability of targeting drug release. [16][17][18] The absolute bioavailability of a poorly soluble drug cyclosporin A which was loaded into a microemulsion system was increased to about 3.3-and 1.25-fold compared with free Sandimmun and Sandimmun Neoral (Novartis, Basel, Switzerland), which were used as commercial cyclosporin A. 19 In addition, it has been confirmed that the microemulsion system containing the poorly soluble drug docetaxel could improve the solubilization property and oral bioavailability of the drug. 20 Presently, there a...

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“…Propranolol was introduced as a marker to determine the transepithelial ability of the established model (Takahashi et al, 2002). Samples were collected from BL side of cell monolayer at 15, 30, 45, 60, 90 and 120 min respectively and analyzed for the propranolol content by high performance liquid chromatography (HPLC) under literature condition (Ma, 2005).…”

Section: The Establishment and Evaluation Of Cell Modelmentioning

confidence: 99%

The Bioavaliability of Hepatoprotective Flavoniods in Hypericum Japonicum Extract

Wang¹,

Peng²

2009

JBABM

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Purpose: To study the absorption of main flavonoids in Hypericum japonicum extract (HJE) with liver protective property; Method: HPLC-ESI-MS was introduced to identify and evaluate the flavonoids in HJE; Caco-2 cell monolayer model was established and validated, and the compounds in HJE, including quercetin (Q), quercetin-3-Orhamnoside (Q-3-R), quercetin-7-O-rhamnoside (Q-7-R) and quercetin-3-O-glucoside (Q-3-G) were administrated in individual, paired or mixed form of the compounds to the monolayer to evaluate their apparent permeability coefficients (P app value). The transport of HJE was also investigated, mixture of pure components and HJE Inhibitor was added to investigate the transport mechanism of the compound mixture. The absorption of the four main ingredients in HJE was then investigated in vivo. Result: transportation of Q, Q-3-R Q-3-G but not Q-7-R trhough Caco-2 monolayer was observed when they were administrated individually. Increase of the transport of Q-3-G and Q-7-R and decrease in Q were observed when the four compounds were given in paired form; when the four flavonoids were given as a whole (either in mixture of pure compounds or in HJE), mass permeability of Q-3-R, Q-7-R and Q-3-G was found. In vivo study identified the in vitro investigation that the major active components of HJE could be absorbed after orally administrated to mice. Conclusion:The increased transport of mixed active components in HJE gives rise to the enhanced hepatoprotetive effect of HJE, and therefore supports the use of botanical drugs.

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Common solubilizers to estimate the Caco-2 transport of poorly water-soluble drugs

Cited by 78 publications

References 17 publications

Water-soluble organic solubilizers for in vitro drug delivery studies with respiratory epithelial cells: Selection based on various toxicity indicators

Water-soluble organic solubilizers for in vitro drug delivery studies with respiratory epithelial cells: Selection based on various toxicity indicators

Enhanced oral bioavailability of a sterol-loaded microemulsion formulation of Flammulina velutipes, a potential antitumor drug

The Bioavaliability of Hepatoprotective Flavoniods in Hypericum Japonicum Extract

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