Drug Solubilization by Mixtures of Cyclodextrins

Additive and Synergistic Effects

Jens Christian Sidney Schönbeck, Karina Gaardahl, Bryan Houston

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Cyclodextrins are popular drug solubilizers, but the use of the natural cyclodextrins is hampered by their tendency to coprecipitate with the drug. To understand and overcome such problems, we have studied the solubility of dexamethasone in the presence of natural β-cyclodextrin and γ-cyclodextrin, individually and in various combinations. Equilibrium models of the phase-solubility diagrams with individual cyclodextrins revealed that dexamethasone was solubilized as 1:1 complexes, but formation of insoluble higher-order complexes set an upper limit to the concentration of solubilized dexamethasone. This limit could be raised from 8 to 17 mM by using combinations of the two cyclodextrins, as their solubilizing properties were additive in some regions of the phase-solubility diagram and synergistic in other regions. The additive effects arise from the additivity of solubilities-the same phenomenon contributes to the good solubilizing properties of many modified cyclodextrins. The synergistic effects, however, could not be explained. The results open up for an increased use of the natural cyclodextrins as an improved alternative to modified cyclodextrins.
Original languageEnglish
JournalMolecular Pharmaceutics
Volume16
Issue number2
Pages (from-to)648-654
Number of pages7
ISSN1543-8384
DOIs
Publication statusPublished - 2019

Cite this

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title = "Drug Solubilization by Mixtures of Cyclodextrins: Additive and Synergistic Effects",
abstract = "Cyclodextrins are popular drug solubilizers, but the use of the natural cyclodextrins is hampered by their tendency to coprecipitate with the drug. To understand and overcome such problems, we have studied the solubility of dexamethasone in the presence of natural β-cyclodextrin and γ-cyclodextrin, individually and in various combinations. Equilibrium models of the phase-solubility diagrams with individual cyclodextrins revealed that dexamethasone was solubilized as 1:1 complexes, but formation of insoluble higher-order complexes set an upper limit to the concentration of solubilized dexamethasone. This limit could be raised from 8 to 17 mM by using combinations of the two cyclodextrins, as their solubilizing properties were additive in some regions of the phase-solubility diagram and synergistic in other regions. The additive effects arise from the additivity of solubilities-the same phenomenon contributes to the good solubilizing properties of many modified cyclodextrins. The synergistic effects, however, could not be explained. The results open up for an increased use of the natural cyclodextrins as an improved alternative to modified cyclodextrins.",
author = "Sch{\"o}nbeck, {Jens Christian Sidney} and Karina Gaardahl and Bryan Houston",
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doi = "10.1021/acs.molpharmaceut.8b00953",
language = "English",
volume = "16",
pages = "648--654",
journal = "Molecular Pharmaceutics",
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Drug Solubilization by Mixtures of Cyclodextrins : Additive and Synergistic Effects. / Schönbeck, Jens Christian Sidney; Gaardahl, Karina; Houston, Bryan.

In: Molecular Pharmaceutics, Vol. 16, No. 2, 2019, p. 648-654.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Drug Solubilization by Mixtures of Cyclodextrins

T2 - Additive and Synergistic Effects

AU - Schönbeck, Jens Christian Sidney

AU - Gaardahl, Karina

AU - Houston, Bryan

PY - 2019

Y1 - 2019

N2 - Cyclodextrins are popular drug solubilizers, but the use of the natural cyclodextrins is hampered by their tendency to coprecipitate with the drug. To understand and overcome such problems, we have studied the solubility of dexamethasone in the presence of natural β-cyclodextrin and γ-cyclodextrin, individually and in various combinations. Equilibrium models of the phase-solubility diagrams with individual cyclodextrins revealed that dexamethasone was solubilized as 1:1 complexes, but formation of insoluble higher-order complexes set an upper limit to the concentration of solubilized dexamethasone. This limit could be raised from 8 to 17 mM by using combinations of the two cyclodextrins, as their solubilizing properties were additive in some regions of the phase-solubility diagram and synergistic in other regions. The additive effects arise from the additivity of solubilities-the same phenomenon contributes to the good solubilizing properties of many modified cyclodextrins. The synergistic effects, however, could not be explained. The results open up for an increased use of the natural cyclodextrins as an improved alternative to modified cyclodextrins.

AB - Cyclodextrins are popular drug solubilizers, but the use of the natural cyclodextrins is hampered by their tendency to coprecipitate with the drug. To understand and overcome such problems, we have studied the solubility of dexamethasone in the presence of natural β-cyclodextrin and γ-cyclodextrin, individually and in various combinations. Equilibrium models of the phase-solubility diagrams with individual cyclodextrins revealed that dexamethasone was solubilized as 1:1 complexes, but formation of insoluble higher-order complexes set an upper limit to the concentration of solubilized dexamethasone. This limit could be raised from 8 to 17 mM by using combinations of the two cyclodextrins, as their solubilizing properties were additive in some regions of the phase-solubility diagram and synergistic in other regions. The additive effects arise from the additivity of solubilities-the same phenomenon contributes to the good solubilizing properties of many modified cyclodextrins. The synergistic effects, however, could not be explained. The results open up for an increased use of the natural cyclodextrins as an improved alternative to modified cyclodextrins.

U2 - 10.1021/acs.molpharmaceut.8b00953

DO - 10.1021/acs.molpharmaceut.8b00953

M3 - Journal article

VL - 16

SP - 648

EP - 654

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

SN - 1543-8384

IS - 2

ER -