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, René

doi:10.1002/jps.24678

Cited by 22 publications

(13 citation statements)

References 52 publications

(70 reference statements)

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“…The complexation efficiency (36) of Lu 35-138 with HP-β-CD, i.e., the product of the association constant (k as ) with the solubility of Lu 35-138 in the medium could provide an idea on whether changes in total drug concentrations directly reflect changes in free drug concentrations. (37). In line with BioGIT data, mean AUC 0-1h and AUC 0-2h values estimated from plasma data increased with the dose (Table III) and the impact of dose was significant (p < 0.001).…”

Section: Lu 35-138c Hp-β-cd Solutionssupporting

confidence: 80%

“…Based on the association constant of itraconazole with HP-betacyclodextrin (approximately 2000 M −1 at pH 7 (38) and the solubility in Level II FaSSIF (0.45 μg/mL) (Fig. 2), complexation efficiency (estimated as described above for Lu 35-138) is very low (0.0013) and changes in total drug concentrations should directly reflect changes in free drug concentrations (37). Therefore, the lack of significant differences between the two Fig.…”

Section: Itraconazole Productsmentioning

confidence: 99%

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The BioGIT System: a Valuable In Vitro Tool to Assess the Impact of Dose and Formulation on Early Exposure to Low Solubility Drugs After Oral Administration

Kourentas

Vertzoni

Barmpatsalou

et al. 2018

AAPS J

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The purpose of this study was to evaluate the usefulness of the in vitro biorelevant gastrointestinal transfer (BioGIT) system in assessing the impact of dose and formulation on early exposure by comparing in vitro data with previously collected human plasma data of low solubility active pharmaceutical ingredients. Eight model active pharmaceutical ingredients were tested; Lu 35-138C (salt of weak base in a HP-beta-CD solution, three doses), fenofibrate (solid dispersion, tablet, two doses), AZD2207 EQ (salt of weak base, capsule, three doses), posaconazole (Noxafil® suspension, two doses), SB705498 (weak base, tablets vs. capsules), cyclosporine A (Sandimmun® vs. Sandimmun® Neoral), nifedipine (Adalat® capsule vs. Macorel® tablet), and itraconazole (Sporanox® capsule vs. Sporanox® solution). AUC values were calculated from the apparent concentration versus time data in the duodenal compartment of the BioGIT system. Differences in AUC values were evaluated versus differences in AUC and in AUC values calculated from previously collected plasma data in healthy adults. Ratios of mean AUC, mean AUC, and mean AUC values were estimated using the lowest dose or the formulation with the lower AUC value as denominator. The BioGIT system qualitatively identified the impact of dose and of formulation on early exposure in all cases. Log-transformed mean BioGIT AUC ratios correlated significantly with log-transformed mean plasma AUC ratios. Based on this correlation, BioGIT AUC ratios between 0.3 and 10 directly reflect corresponding plasma AUC ratios. BioGIT system is a valuable tool for the assessment of the impact of dose and formulation on early exposure to low solubility drugs.

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Section: Lu 35-138c Hp-β-cd Solutionssupporting

confidence: 80%

Section: Itraconazole Productsmentioning

confidence: 99%

The BioGIT System: a Valuable In Vitro Tool to Assess the Impact of Dose and Formulation on Early Exposure to Low Solubility Drugs After Oral Administration

Kourentas

Vertzoni

Barmpatsalou

et al. 2018

AAPS J

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“…Analysis of the results showed that the direct interactions between the bile salt micelles and CDs were insignificant. From this knowledge, an extended form of Stella’s CDs utility number (UCD), was suggested to achieve total drug solubilization in the intestine where bile salts are present [60]. In another study, the pharmacokinetics of two complexed substances, danazol—which has high affinity for HP-β-CD and cinnarizine—which has low to medium affinity, were measured in vivo.…”

Section: In Vivo Cyclodextrin Studiesmentioning

confidence: 99%

Cyclodextrin–Drug Inclusion Complexes: In Vivo and In Vitro Approaches

Carneiro

Duarte

Heimfarth

et al. 2019

IJMS

264

168

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This review aims to provide a critical review of the biological performance of natural and synthetic substances complexed with cyclodextrins, highlighting: (i) inclusion complexes with cyclodextrins and their biological studies in vitro and in vivo; (ii) Evaluation and comparison of the bioactive efficacy of complexed and non-complexed substances; (iii) Chemical and biological performance tests of inclusion complexes, aimed at the development of new pharmaceutical products. Based on the evidence presented in the review, it is clear that cyclodextrins play a vital role in the development of inclusion complexes which promote improvements in the chemical and biological properties of the complexed active principles, as well as providing improved solubility and aqueous stability. Although the literature shows the importance of their ability to help produce innovative biotechnological substances, we still need more studies to develop and expand their therapeutic properties. It is, therefore, very important to gather together evidence of the effectiveness of inclusion complexes with cyclodextrins in order to facilitate a better understanding of research on this topic and encourage further studies.

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“…Depending on the exact reaction conditions, three main types of CDs are obtained, α-, β-, and γ-CD, each comprises six to eight dextrose units respectively. 17 CDs are ring molecules which lack free rotation at the level of bonds between glucopyranose units, they are not cylindrical rather they are toroidal or cone shaped. CDs consists of hollow tapered cavity consist of 0.79 nm in depth in which the active molecule is incorporated.…”

Section: Structure Of Cdsmentioning

confidence: 99%

“…Due to this characteristics nature, CDs have attained a great interest as a solubilising candidate and has overcome the biopharmaceutical deficiencies of various drugs in the recent years. 14,[17][18][19] CDs are widely soluble in some polar, aprotic solvents, but insoluble in most organic solvents. 20 Although, CDs exhibit higher solubility in some of the organic solvents than in water, inclusion complexes do not take place in non-aqueous solvents because of the increased affinity of guest molecule for the solvent compared to its affinity for water.…”

Section: Structure Of Cdsmentioning

confidence: 99%

Cyclodextrin: A Promising Candidate in Enhancing Oral Bioavailability of poorly Water Soluble Drugs

Maheriya¹

2017

MOJBB

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Most of the drugs administered through oral route have poor aqueous solubility and dissolution rate. Cyclodextrin and its derivates represent as pharmaceutical adjuvants to overcome this challenges and helps in development of stable formulation with enhanced bioavailability. Cyclodextrins are unique structure with versatile physicochemical properties which aids the pharmaceutical scientists to overcome drug delivery challenges for poorly aqueous soluble drugs. Cyclodextrin and its derivates are widely useful as solubilizers, assisting in preparation of various dosage forms such as liquid oral, solid, and parenteral preparations. Cyclodextrins interacts with appropriately sized guest molecules to form inclusion complex and enhance the aqueous solubility, physical chemical stability, and bioavailability of drugs. Through the various reported literatures, the review highlights the concept of cyclodextrin and its derivatives in enhancing solubility and bioavailability of poorly aqueous soluble drugs.

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Displacement of Drugs From Cyclodextrin Complexes by Bile Salts: A Suggestion of an Intestinal Drug-Solubilizing Capacity From an In Vitro Model

Cited by 22 publications

References 52 publications

The BioGIT System: a Valuable In Vitro Tool to Assess the Impact of Dose and Formulation on Early Exposure to Low Solubility Drugs After Oral Administration

The BioGIT System: a Valuable In Vitro Tool to Assess the Impact of Dose and Formulation on Early Exposure to Low Solubility Drugs After Oral Administration

Cyclodextrin–Drug Inclusion Complexes: In Vivo and In Vitro Approaches

Cyclodextrin: A Promising Candidate in Enhancing Oral Bioavailability of poorly Water Soluble Drugs

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