Displacement of Drugs From Cyclodextrin Complexes by Bile Salts

A Suggestion of an Intestinal Drug-Solubilizing Capacity From an In Vitro Model

Niels Erik Olesen, Peter Westh, Rene Holm

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

The dosing of drugs in an aqueous cyclodextrin formulation requires sufficient amount of cyclodextrins to fully solubilize the drug, as described by Stella's cyclodextrin utility number (UCD). However, this framework does not take biopharmaceutical elements into account, such as the displacement of drug from the cyclodextrin cavity by bile salts present in the small intestine. As bile salts in the intestine are present at concentrations above the critical micelle concentration, an understanding of the interaction between cyclodextrins and bile salts at such supramicellar concentrations (SMC) is required for a better biopharmaceutical understanding of the release mechanism from orally dosed cyclodextrin complexes. To address this, experiments were conducted by isothermal titration calorimetry to determine how various b-cyclodextrins and bile salt interacts at SMC. Combined analysis of the current results and earlier data demonstrated that direct interactions between bile salt micelles and cyclodextrin were negligible. From this knowledge, an extended form of the UCD was suggested to describe the concentration of cyclodextrins to achieve full drug solubilization in the intestine where bile salts are present. Dosing cyclodextrins above this limit will diminish the free drug concentration, potentially decreasing the amount of drug absorbed.
OriginalsprogEngelsk
TidsskriftJournal of Pharmaceutical Sciences
Vol/bind105
Udgave nummer9
Sider (fra-til)2640-2647
ISSN0022-3549
DOI
StatusUdgivet - 2016

Emneord

  • mathematical model
  • solubilization
  • bile salts
  • cyclodextrin
  • calorimetry (ITC)
  • complexation
  • micelle
  • intestinal absorption

Citer dette

@article{ec3605656c434cc2a51af44862b41f32,
title = "Displacement of Drugs From Cyclodextrin Complexes by Bile Salts: A Suggestion of an Intestinal Drug-Solubilizing Capacity From an In Vitro Model",
abstract = "The dosing of drugs in an aqueous cyclodextrin formulation requires sufficient amount of cyclodextrins to fully solubilize the drug, as described by Stella's cyclodextrin utility number (UCD). However, this framework does not take biopharmaceutical elements into account, such as the displacement of drug from the cyclodextrin cavity by bile salts present in the small intestine. As bile salts in the intestine are present at concentrations above the critical micelle concentration, an understanding of the interaction between cyclodextrins and bile salts at such supramicellar concentrations (SMC) is required for a better biopharmaceutical understanding of the release mechanism from orally dosed cyclodextrin complexes. To address this, experiments were conducted by isothermal titration calorimetry to determine how various b-cyclodextrins and bile salt interacts at SMC. Combined analysis of the current results and earlier data demonstrated that direct interactions between bile salt micelles and cyclodextrin were negligible. From this knowledge, an extended form of the UCD was suggested to describe the concentration of cyclodextrins to achieve full drug solubilization in the intestine where bile salts are present. Dosing cyclodextrins above this limit will diminish the free drug concentration, potentially decreasing the amount of drug absorbed.",
keywords = "mathematical model, solubilization, bile salts, cyclodextrin, calorimetry (ITC), complexation, micelle, intestinal absorption, mathematical model, solubilization, bile salts, cyclodextrin, calorimetry (ITC), complexation, micelle, intestinal absorption",
author = "Olesen, {Niels Erik} and Peter Westh and Rene Holm",
year = "2016",
doi = "10.1002/jps.24678",
language = "English",
volume = "105",
pages = "2640--2647",
journal = "Journal of Pharmaceutical Sciences",
issn = "0022-3549",
publisher = "Elsevier Inc.",
number = "9",

}

Displacement of Drugs From Cyclodextrin Complexes by Bile Salts : A Suggestion of an Intestinal Drug-Solubilizing Capacity From an In Vitro Model . / Olesen, Niels Erik; Westh, Peter; Holm, Rene.

I: Journal of Pharmaceutical Sciences, Bind 105, Nr. 9, 2016, s. 2640-2647 .

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Displacement of Drugs From Cyclodextrin Complexes by Bile Salts

T2 - A Suggestion of an Intestinal Drug-Solubilizing Capacity From an In Vitro Model

AU - Olesen, Niels Erik

AU - Westh, Peter

AU - Holm, Rene

PY - 2016

Y1 - 2016

N2 - The dosing of drugs in an aqueous cyclodextrin formulation requires sufficient amount of cyclodextrins to fully solubilize the drug, as described by Stella's cyclodextrin utility number (UCD). However, this framework does not take biopharmaceutical elements into account, such as the displacement of drug from the cyclodextrin cavity by bile salts present in the small intestine. As bile salts in the intestine are present at concentrations above the critical micelle concentration, an understanding of the interaction between cyclodextrins and bile salts at such supramicellar concentrations (SMC) is required for a better biopharmaceutical understanding of the release mechanism from orally dosed cyclodextrin complexes. To address this, experiments were conducted by isothermal titration calorimetry to determine how various b-cyclodextrins and bile salt interacts at SMC. Combined analysis of the current results and earlier data demonstrated that direct interactions between bile salt micelles and cyclodextrin were negligible. From this knowledge, an extended form of the UCD was suggested to describe the concentration of cyclodextrins to achieve full drug solubilization in the intestine where bile salts are present. Dosing cyclodextrins above this limit will diminish the free drug concentration, potentially decreasing the amount of drug absorbed.

AB - The dosing of drugs in an aqueous cyclodextrin formulation requires sufficient amount of cyclodextrins to fully solubilize the drug, as described by Stella's cyclodextrin utility number (UCD). However, this framework does not take biopharmaceutical elements into account, such as the displacement of drug from the cyclodextrin cavity by bile salts present in the small intestine. As bile salts in the intestine are present at concentrations above the critical micelle concentration, an understanding of the interaction between cyclodextrins and bile salts at such supramicellar concentrations (SMC) is required for a better biopharmaceutical understanding of the release mechanism from orally dosed cyclodextrin complexes. To address this, experiments were conducted by isothermal titration calorimetry to determine how various b-cyclodextrins and bile salt interacts at SMC. Combined analysis of the current results and earlier data demonstrated that direct interactions between bile salt micelles and cyclodextrin were negligible. From this knowledge, an extended form of the UCD was suggested to describe the concentration of cyclodextrins to achieve full drug solubilization in the intestine where bile salts are present. Dosing cyclodextrins above this limit will diminish the free drug concentration, potentially decreasing the amount of drug absorbed.

KW - mathematical model

KW - solubilization

KW - bile salts

KW - cyclodextrin

KW - calorimetry (ITC)

KW - complexation

KW - micelle

KW - intestinal absorption

KW - mathematical model

KW - solubilization

KW - bile salts

KW - cyclodextrin

KW - calorimetry (ITC)

KW - complexation

KW - micelle

KW - intestinal absorption

U2 - 10.1002/jps.24678

DO - 10.1002/jps.24678

M3 - Journal article

VL - 105

SP - 2640

EP - 2647

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

IS - 9

ER -