An In Vitro Methodology for Forecasting Luminal Concentrations and Precipitation of Highly Permeable Lipophilic Weak Bases in the Fasted Upper Small Intestine

Psachoulias, Dimitrios; Vertzoni, Maria; Butler, James; Busby, David J.; Symillides, Moira; Dressman, Jennifer B.; Reppas, Christos

doi:10.1007/s11095-012-0844-z

Cited by 86 publications

(77 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most of the smTKIs are weak bases (pK a -values in Table 2) which are protonated, and as such most soluble, in acidic environments [74]. The increase in pH-values encountered in the intestines dramatically decreases their solubility [75]. The result of this is a relative high solubility in the stomach, but a significantly lower one in the intestinal lumen.…”

Section: Solubilitymentioning

confidence: 99%

Variability in bioavailability of small molecular tyrosine kinase inhibitors

Herbrink

Nuijen

Schellens

et al. 2015

Cancer Treatment Reviews

111

104

View full text Add to dashboard Cite

Section: Solubilitymentioning

confidence: 99%

Variability in bioavailability of small molecular tyrosine kinase inhibitors

Herbrink

Nuijen

Schellens

et al. 2015

Cancer Treatment Reviews

111

104

View full text Add to dashboard Cite

“…Recently, FaSSIF-V2Plus was proposed for predicting the precipitation of weak bases in the upper small doi: 10.5599/admet.2.2.40 73 intestine [4]. In the present investigation, all these media were prepared by using crude bile material (ox bile salt extract) and used for measuring the solubility of the four model APIs ( Table 1).…”

Section: Methodsmentioning

confidence: 99%

“…To date, the importance of certain luminal components which may have an impact on luminal solubility of lipophilic APIs in the fasted state, such as fatty acids, cholesterol and 72 proteins, has not been considered. Such components have been recently shown to have a role in luminal precipitation of lipophilic weak bases [4].…”

Section: Introductionmentioning

confidence: 99%

Increasing the biorelevance of simulated intestinal fluids for better predictions of drug equilibrium solubility in the fasted upper small intestine

Koumandrakis¹,

Vertzoni²,

Reppas³

2014

ADMET DMPK

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the second apparatus, however, pH, volume and the composition of the duodenal fluid were all left without intervention [65,148]. Psachoulias et al [149] presented an improved method, where although a gastric and a duodenal compartment were used, the dilution of the duodenal fluid which was the FaSSIF V2 plus was compensated by an inflow of a concentrated medium from a third vessel.…”

Section: Dissolution Apparatusesmentioning

confidence: 99%

Drug release from matrix tablets: physiological parameters and the effect of food

Nokhodchi

Asare-Addo

2014

Expert Opinion on Drug Delivery

View full text Add to dashboard Cite

Introduction: As dissolution plays an important and vital role in the drug-delivery process of oral solid dosage forms, it is, therefore, essential to critically evaluate the parameters that can affect this process. Areas covered:The consumption of food as well as the physiological environment and properties of the gastrointestinal tract, such as its volume and composition of fluid, the fluid hydrodynamics, properties of the intestinal membrane, drug dose and solubility, pK a , diffusion coefficient, permeability and particle size, all affect drug dissolution and absorption rate. There are several dissolution approaches that have been developed to address the conditions as experienced in the in vivo environment, as the traditional dissolution being a quality control method is not biorelevant and as such do not always produce meaningful data. This review also describes the development of a systematic way that differentiates between robust and non-robust formulations by varying the effects of agitation and ionic strength through the use of the automated United States Pharmacopeia type III Bio-Dis apparatus. Expert opinion:With the improved understanding of the physiological parameters that can affect the oral bioperformance of dosage forms, strides have, therefore, been made in making dissolution testing methods more bio-logically based with the view of obtaining more in vitro--in vivo correlations.Keywords: agitation rate, biodissolution, drug release, effect of food, hydrophilic matrices, ionic strength Highlights -Understanding all the physiological parameters can serve as a basis for designing dissolution testing methods and systems that can more fully represent the gastrointestinal (GI) tract in humans and allow more in vitro-in vivo (IVIVC) correlations to be obtained thereby improving the oral bioperformance of dosage forms.-Simulation of GI conditions is essential to adequately predict the in vivo behaviour of drug formulations.-The choice of appropriate media for in vitro tests is crucial to their ability to correctly forecast the food effect in pharmacokinetic studies.-Several methods of dissolution testing have been conducted and are still ongoing that seek to further understand and develop media and dissolution methods to better represent the in vivo conditions and to aid in the better prediction of in vivo drug release.-Systematic change of agitation method and ionic strength evaluation may be used as additional tools in allowing for the identification of potential fed and fasted effects on drug release from hydrophilic matrices in the drive for developing dissolution methodologies that are more relevant in helping to achieve more IVIVC.

show abstract

An In Vitro Methodology for Forecasting Luminal Concentrations and Precipitation of Highly Permeable Lipophilic Weak Bases in the Fasted Upper Small Intestine

Cited by 86 publications

References 23 publications

Variability in bioavailability of small molecular tyrosine kinase inhibitors

Variability in bioavailability of small molecular tyrosine kinase inhibitors

Increasing the biorelevance of simulated intestinal fluids for better predictions of drug equilibrium solubility in the fasted upper small intestine

Drug release from matrix tablets: physiological parameters and the effect of food

Contact Info

Product

Resources

About