Prediction of the permeability of drugs through study on quantitative structure–permeability relationship

Jung, Seo Jeong; Choi, Sun Ok; Um, So Young; Kim, Joo Il; Choo, Hae Young Park; Choi, Sang Hyoun; Chung, Soo Youn

doi:10.1016/j.jpba.2005.12.020

Cited by 46 publications

(23 citation statements)

References 10 publications

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“…Reduction in Papp for treatments 1 and 4 were significant compared to IND control (p<0.05, ANOVA/Tukey's), whilst differences in Papp between the two treatments were insignificant (p>0.05, ANOVA/Tukey's). Papp values indicated medium to high permeability of IND and were intermediate of those previously reported for IND using Caco-2 models (ElShaer et al, 2014;Jin et al, 2014;Jung et al, 2006). Also, these results are in agreement with a previous report for famotidine loaded MPs and dexamethasone loaded NPs coated MPs transport across Caco-2 cell monolayers (Beck et al, 2007;Degim et al, 2005).…”

Section: Permeability and Transport Studysupporting

confidence: 90%

Colonic delivery of indometacin loaded PGA-co-PDL microparticles coated with Eudragit L100-55 from fast disintegrating tablets

Tawfeek

Abdellatif

Dennison

et al. 2017

International Journal of Pharmaceutics

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The aim of this work was to investigate the efficient targeting and delivery of indometacin (IND), as a model anti-inflammatory drug to the colon for treatment of inflammatory bowel disease. We prepared fast disintegrating tablets (FDT) containing IND encapsulated within poly(glycerol-adipate-co-ɷ-pentadecalactone), PGA-co-PDL, microparticles and coated with Eudragit L100-55 at different ratios (1:1.5, 1:1, 1:0.5). Microparticles encapsulated with IND were prepared using an o/w single emulsion solvent evaporation technique and coated with Eudragit L-100-55 via spray drying. The produced coated microparticles (PGA-co-PDL-IND/Eudragit) were formulated into optimised FTD using a single station press. The loading, in vitro release, permeability and transport of IND from PGA-co-PDL-IND/Eudragit microparticles was studied in Caco-2 cell lines. IND was efficiently encapsulated (570.15±4.2μg/mg) within the PGA-co-PDL microparticles. In vitro release of PGA-co-PDL-IND/Eudragit microparticles (1:1.5) showed significantly (p<0.05, ANOVA/Tukey) lower release of IND 13.70±1.6 and 56.46±3.8% compared with 1:1 (89.61±2.5, 80.13±2.6%) and 1:0.5 (39.46±0.9 & 43.38±3.12) after 3 and 43h at pH 5.5 and 6.8, respectively. The permeability and transport studies indicated IND released from PGA-co-PDL-IND/Eudragit microparticles had a lower permeability coefficient of 13.95±0.68×10cm/s compared to free IND 23.06±3.56×10cm/s. These results indicate the possibility of targeting anti-inflammatory drugs to the colon using FDTs containing microparticles coated with Eudragit.

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Section: Permeability and Transport Studysupporting

confidence: 90%

Colonic delivery of indometacin loaded PGA-co-PDL microparticles coated with Eudragit L100-55 from fast disintegrating tablets

Tawfeek

Abdellatif

Dennison

et al. 2017

International Journal of Pharmaceutics

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“…These markedly lower levels of olopatadine in the aqueous humor compared to the conjunctiva/cornea in both the treatment groups could be due to low permeation across the cornea consistent with the low logP'oct value of 0.3 in the BrittonRobinson buffer (pH 7.4). 7,8 This observation further suggests that olopatadine is able to penetrate the outer mucous layer, but primarily resides in the epithelium-tethered mucins (glycocalyx) thereby acting as an ocular surface agent.…”

Section: Discussionmentioning

confidence: 94%

Ocular Pharmacokinetics Comparison Between 0.2% Olopatadine and 0.77% Olopatadine Hydrochloride Ophthalmic Solutions Administered to Male New Zealand White Rabbits

Iyer

Cason

Womble

et al. 2015

Journal of Ocular Pharmacology and Therapeutics

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“…1. Effect of inclusion of amino acid and peptide transporter substrates on the in vitro-in vivo correlations of Caco-2 and human intestinal permeability measurements for eight studies (29)(30)(31)(32)(33)(34)(35)(36), where Caco-2 permeability measurements were available for at least 6 drugs, including metoprolol, of the 30 drugs with available human intestinal permeability measurements. The total number of compounds in each correlation range from 6 to 22, with the average being 11 correlations (Fig.…”

Section: Identifying Compounds For Which Caco-2 May Poorly Predict Humentioning

confidence: 99%

“…To help understand the impact of selecting Caco-2 permeability data from multiple sources to develop an in silico model, Fig. 2 illustrates the degree of variability in Caco-2 permeability measurements for 20 out of 30 drugs, that is those drugs for which both human intestinal permeability rate measurements are available (4) and multiple sources report their Caco-2 permeability measurements (8,20,(29)(30)(31)(32)(33)(34)(35)(36)79). Permeability values for each compound were included if metoprolol had also been studied in the Caco-2 evaluation to determine if the observed interlaboratory variability could be mitigated when the measurements were normalized to a reference standard.…”

Section: The Need For Larger Single-source Caco-2 Permeability Datasetsmentioning

confidence: 99%

Drug Discovery and Regulatory Considerations for Improving In Silico and In Vitro Predictions that Use Caco-2 as a Surrogate for Human Intestinal Permeability Measurements

Larregieu

Benet

2013

AAPS J

131

119

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ABSTRACT. There is a growing need for highly accurate in silico and in vitro predictive models to facilitate drug discovery and development. Results from in vitro permeation studies across the Caco-2 cell monolayer are commonly used for drug permeability screening in industry and are also accepted as a surrogate for human intestinal permeability measurements by the US FDA to support new drug applications. Countless studies carried out in this cell line with published permeability measurements have enabled the development of many in silico prediction models. We identify several common cases that illustrate how using Caco-2 permeability measurements in these in silico and in vitro predictive models will not correlate with human intestinal permeability and will further lead to inaccuracies in these models. We provide guidelines and recommendations for improving these models to more accurately predict clinically relevant information, thereby enhancing the drug discovery, development, and regulatory approval processes.

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Prediction of the permeability of drugs through study on quantitative structure–permeability relationship

Cited by 46 publications

References 10 publications

Colonic delivery of indometacin loaded PGA-co-PDL microparticles coated with Eudragit L100-55 from fast disintegrating tablets

Colonic delivery of indometacin loaded PGA-co-PDL microparticles coated with Eudragit L100-55 from fast disintegrating tablets

Ocular Pharmacokinetics Comparison Between 0.2% Olopatadine and 0.77% Olopatadine Hydrochloride Ophthalmic Solutions Administered to Male New Zealand White Rabbits

Drug Discovery and Regulatory Considerations for Improving In Silico and In Vitro Predictions that Use Caco-2 as a Surrogate for Human Intestinal Permeability Measurements

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