Untitled

Wiedmann, Timothy S.; Liang, Wei; Kamel, Lamya

doi:10.1023/a:1019858428449

Cited by 55 publications

(20 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several studies have demonstrated a correlation between drug lipophilicity and improved compound solubility in biorelevant media relative to the corresponding intrinsic water solubility (15)(16)(17)(18). Addition of FA and MG, which are formed during digestion of triglycerides, can simulate the fed state.…”

Section: Introductionmentioning

confidence: 99%

Colloidal Structures in Media Simulating Intestinal Fed State Conditions with and Without Lipolysis Products

et al. 2008

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

Colloidal Structures in Media Simulating Intestinal Fed State Conditions with and Without Lipolysis Products

et al. 2008

View full text Add to dashboard Cite

show abstract

“…The CMC of the mixed micellar system was deemed to be 0.0046 M based on the average value of the CMCs of the bile salts included in the mixture in 0.15 M NaCl [NaTC CMC = 0.004 M (Natalini et al, 2014), NaDC CMC = 0.0024 M (Natalini et al, 2014), NaTDC CMC = 0.0024 M (Natalini et al, 2014), NaC CMC = 0.0075 M (Reis et al, 2004), NaGC CMC = 0.009 M (Natalini et al, 2014) and NaGDC CMC = 0.0022 M (Natalini et al, 2014)]. The bile salt–lecithin mixed micellar solution was used over a concentration range 0.005–0.017 M. The mixed micellar system was prepared in molar ratios similar to that present physiologically (Wiedmann et al, 2002). …”

Section: Resultsmentioning

confidence: 99%

“…The resultant solution was sonicated for 30 min then stored for 12 h before use. Dilution was carried out in this way as the 2 mM mixture is considered to be the monomer bile salt concentration that is required to be kept constant in each solution in order to keep the size of the micelle constant while its concentration is being changed (Wiedmann et al, 2002). …”

Section: Methodsmentioning

confidence: 99%

“…The novelty of the work presented in this study lies in the use of a very unique mobile phase mimicking the in vivo intestinal environment of humans. The composition of this mobile phase was closely related to that of the intestinal fluid through a combination of lecithin and bile salts which are normally found in the human intestine, used in ratios matching those found physiologically (Wiedmann, Liang, & Kamel, 2002). …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Incorporating physiologically relevant mobile phases in micellar liquid chromatography for the prediction of human intestinal absorption

Shokry

Waters

Parkes

et al. 2018

Biomedical Chromatography

View full text Add to dashboard Cite

Micellar liquid chromatography is a popular method used in the determination of a compound's lipophilicity. This study describes the use of the obtained micelle–water partition coefficient (log P mw) by such a method in the prediction of human intestinal absorption (HIA). As a result of the close resemblance of the novel composition of the micellar mobile phase to that of physiological intestinal fluid, prediction was deemed to be highly successful. The unique micellar mobile phase consisted of a mixed micellar mixture of lecithin and six bile salts, i.e. a composition matching that found in the human intestinal environment, prepared in ratios resembling those in the intestine. This is considered to be the first method to use a physiological mixture of biosurfactants in the prediction of HIA. As a result, a mathematical model with high predictive ability (R 2 PRED = 81%) was obtained using multiple linear regression. The micelle–water partition coefficient (log P mw) obtained from micellar liquid chromatography was found to be a successful tool for prediction where the final optimum model included log P mw and polar surface area as key descriptors with high statistical significance for the prediction of HIA. This can be attributed to the nature of the mobile phase used in this study which contains the lecithin–bile salt complex, thus forming a bilayer system and therefore mimicking absorption across the intestinal membrane.

show abstract

“…However, over 50% of the drugs considered to be potential candidates in the full development pipeline are poorly soluble in aqueous solutions, and more than 30% are rejected because of unfavourable pharmacokinetic properties [37,38]. Numerous methods have been developed to improve solubility and bioavailability of drugs [39][40][41][42][43][44].…”

Section: Introductionmentioning

confidence: 99%

Characterization of pharmaceutical drugs by a modified nonaqueous capillary electrophoresis – mass spectrometry method

et al. 2003

View full text Add to dashboard Cite

A simple method for the separation and characterization of a group of nine basic compounds, comprising seven tricyclic antidepressant and two bronchodilator drugs, by nonaqueous capillary electrophoresis (NACE) employing ultraviolet and mass spectrometry detection is described. After optimization of the electrophoresis separation conditions, including the compositions of the electrolyte and the organic solvent, a reliable separation of all nine basic analytes was achieved in 80 mM ammonium formate dissolved in a methanol-acetonitrite (80:20 v/v) mixture, having an apparent pH of 8.7. The volatile nonaqueous electrolyte system used with a normal electroosmotic flow polarity also provided an optimal separation condition for the characterization of the analytes by mass spectrometry. When results were compared with reversed-phase gradient and isocratic high-performance liquid chromatography (HPLC) methods, the NACE method provided greater efficiency, achieving baseline resolution for all nine basic compounds in less than 30 min. The NACE method is suitable for use as a routine procedure for the rapid separation and characterization of basic compounds and is a viable alternative to HPLC for the separation of a wide range of pharmaceutical drugs.

show abstract

Untitled

Abstract: With such data, a refined, predictive relationship between the in vitro and the in vivo solubilization with additional information concerning the bile salt/lipid concentration in the human intestine appears possible.

Cited by 55 publications

References 13 publications

Colloidal Structures in Media Simulating Intestinal Fed State Conditions with and Without Lipolysis Products

Colloidal Structures in Media Simulating Intestinal Fed State Conditions with and Without Lipolysis Products

Incorporating physiologically relevant mobile phases in micellar liquid chromatography for the prediction of human intestinal absorption

Characterization of pharmaceutical drugs by a modified nonaqueous capillary electrophoresis – mass spectrometry method

Contact Info

Product

Resources

About