Permeability assessment of poorly water‐soluble compounds under solubilizing conditions: The reciprocal permeability approach

Katneni, Kasiram; Charman, Susan A.; Porter, Christopher John

doi:10.1002/jps.20687

Cited by 54 publications

(68 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the micellar solubilization which gives rise to this important apparent solubility enhancement also results in decreased free fraction of drug. Similar to the case of cyclodextrins, this incorporation of drug in micelles significantly decreases the amount of free drug available for permeation through the intestinal membrane (31,32,34,35,(40)(41)(42).…”

Section: S-p Interplay From Surfactant-based Systemsmentioning

confidence: 93%

“…Previous studies have shown that the use of surfactants may lead to increased, decreased, or unchanged membrane permeability (31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42). It is important to note that surfactants may increase intestinal membrane permeability for drugs with inherently low-permeability and high aqueous solubility (i.e., BCS class III compounds), e.g., through the disruption of membrane integrity to increase paracellular transport (e.g., tight junction opening, which may induce potentially toxic effects) and/or the inhibition of efflux transporters (36,39,(42)(43)(44)(45).…”

Section: S-p Interplay From Surfactant-based Systemsmentioning

confidence: 99%

See 1 more Smart Citation

The Solubility–Permeability Interplay and Its Implications in Formulation Design and Development for Poorly Soluble Drugs

Dahan

Miller

2012

AAPS J

225

130

View full text Add to dashboard Cite

Abstract. While each of the two key parameters of oral drug absorption, the solubility and the permeability, has been comprehensively studied separately, the relationship and interplay between the two have been largely ignored. For instance, when formulating a low-solubility drug using various solubilization techniques: what are we doing to the apparent permeability when we increase the solubility? Permeability is equal to the drug's diffusion coefficient through the membrane times the membrane/aqueous partition coefficient divided by the membrane thickness. The direct correlation between the intestinal permeability and the membrane/aqueous partitioning, which in turn is dependent on the drug's apparent solubility in the GI milieu, suggests that the solubility and the permeability are closely associated, exhibiting a certain interplay between them, and the current view of treating the one irrespectively of the other may not be sufficient. In this paper, we describe the research that has been done thus far, and present new data, to shed light on this solubility-permeability interplay. It has been shown that decreased apparent permeability accompanies the solubility increase when using different solubilization methods. Overall, the weight of the evidence indicates that the solubility-permeability interplay cannot be ignored when using solubility-enabling formulations; looking solely at the solubility enhancement that the formulation enables may be misleading with regards to predicting the resulting absorption, and hence, the solubility-permeability interplay must be taken into account to strike the optimal solubility-permeability balance, in order to maximize the overall absorption.

show abstract

Section: S-p Interplay From Surfactant-based Systemsmentioning

confidence: 93%

Section: S-p Interplay From Surfactant-based Systemsmentioning

confidence: 99%

The Solubility–Permeability Interplay and Its Implications in Formulation Design and Development for Poorly Soluble Drugs

Dahan

Miller

2012

AAPS J

225

130

View full text Add to dashboard Cite

show abstract

“…In this context, it is rec-906 ognized that only free drug molecules provide the driving force for ab-907 sorption, and that solubilization by micelles will lead to a decrease in 908 the absorption kinetics [84]. Consequently, it has been pointed out 909 that erroneous estimates of drug permeability will result if micelles 910 are present, and calculations are performed using total instead of free 911 drug concentration [85]. ity.…”

mentioning

confidence: 99%

“…1) of a 854 compound represents the upper limit of achievable supersaturation. 855 Therefore, knowledge of the amorphous-to-crystalline solubility ratio 877 Micellar solubilization has been described in detail previously [19], 878 and only those aspects pertinent to this review will be briefly discussed the micelle relative to its affinity for the aqueous phase and is given by: given concentration of micellar surfactant can then described by [19]: the context of permeability assessment [84,85]. In this context, it is rec-906 ognized that only free drug molecules provide the driving force for ab-907 sorption, and that solubilization by micelles will lead to a decrease in 908 the absorption kinetics [84].…”

mentioning

confidence: 99%

Physical chemistry of supersaturated solutions and implications for oral absorption

Taylor

Zhang

2016

Advanced Drug Delivery Reviews

293

298

View full text Add to dashboard Cite

“…-The effect of micelles on effective permeability was previously investigated by in vitro [29] [30], ex-vivo [31], and in vivo experiments [32]. Micelle partitioning has a significant effect on permeability, due to 1) a decrease in the diffusion of a drug across the mUWL, and 2) a decrease in the free monomer fraction at the epithelial membrane surface (Fig.…”

Section: Effective Intestinal Membranementioning

confidence: 99%

Computational Oral Absorption Simulation for Low‐Solubility Compounds

Sugano

2009

Chemistry & Biodiversity

View full text Add to dashboard Cite

Bile micelles play an important role in oral absorption of low-solubility compounds. Bile micelles can affect solubility, dissolution rate, and permeability. For the pH-solubility profile in bile micelles, the Henderson-Hasselbalch equation should be modified to take bile-micelle partition into account. For the dissolution rate, in the Nernst-Brunner equation, the effective diffusion coefficient in bile-micelle media should be used instead of the monomer diffusion coefficient. The diffusion coefficient of bile micelles is 8- to 18-fold smaller than that of monomer molecules. For permeability, the effective diffusion coefficient in the unstirred water layer adjacent to the epithelial membrane, and the free fraction at the epithelial membrane surface should be taken into account. The importance of these aspects is demonstrated here using several in vivo and clinical oral-absorption data of low-solubility model compounds. Using the theoretical equations, the food effect on oral absorption is further discussed.

show abstract

Permeability assessment of poorly water‐soluble compounds under solubilizing conditions: The reciprocal permeability approach

Cited by 54 publications

References 40 publications

The Solubility–Permeability Interplay and Its Implications in Formulation Design and Development for Poorly Soluble Drugs

The Solubility–Permeability Interplay and Its Implications in Formulation Design and Development for Poorly Soluble Drugs

Physical chemistry of supersaturated solutions and implications for oral absorption

Computational Oral Absorption Simulation for Low‐Solubility Compounds

Contact Info

Product

Resources

About