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Drug Release from ß-Cyclodextrin Complexes and Drug Transfer into Model Membranes Studied by Affinity Capillary Electrophoresis

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Abstract

Purpose

Is to characterize the drug release from the ß-cyclodextrin (ß-CD) cavity and the drug transfer into model membranes by affinity capillary electrophoresis. Phospholipid liposomes with and without cholesterol were used to mimic the natural biological membrane.

Methods

The interaction of cationic and anionic drugs with ß-CD and the interaction of the drugs with liposomes were detected separately by measuring the drug mobility in ß-CD containing buffer and liposome containing buffer; respectively. Moreover, the kinetics of drug release from ß-CD and its transfer into liposomes with or without cholesterol was studied by investigation of changes in the migration behaviours of the drugs in samples, contained drug, ß-CD and liposome, at 1:1:1 molar ratio at different time intervals; zero time, 30 min, 1, 2, 4, 6, 8, 10 and 24 h. Lipophilic drugs such as propranolol and ibuprofen were chosen for this study, because they form complexes with ß-CD.

Results

The mobility of the both drug liposome mixtures changed with time to a final state. For samples of liposomal membranes with cholesterol the final state was faster reached than without cholesterol.

Conclusions

The study confirmed that the drug release from the CD cavity and its transfer into the model membrane was more enhanced by the competitive displacement of the drug from the ß-CD cavity by cholesterol, the membrane component. The ACE method here developed can be used to optimize the drug release from CD complexes and the drug transfer into model membranes.

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Abbreviations

ACE:

Affinity capillary electrophoresis

CD:

Cyclodextrin

IBU:

Ibuprofen

LD :

The distance from the capillary inlet to the detector

LT :

The total length of the capillary

PC:

Phosphatidylcholine

Pro:

Propranolol

PS:

Phosphatidylserine

tEOF :

The migration time of electroosmotic flow peak

tm :

The migration time of drug peak

U:

The applied voltage

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Authors and Affiliations

  1. Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120, Halle (Saale), Germany

    Kinda A. Darwish, Hans-Hermann Rüttinger & Reinhard H. H. Neubert

  2. Institute of Applied Dermatopharmacy, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany

    Yahya Mrestani & Reinhard H. H. Neubert

Authors
  1. Kinda A. Darwish
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  2. Yahya Mrestani
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  3. Hans-Hermann Rüttinger
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  4. Reinhard H. H. Neubert
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Correspondence to Kinda A. Darwish.

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Darwish, K.A., Mrestani, Y., Rüttinger, HH. et al. Drug Release from ß-Cyclodextrin Complexes and Drug Transfer into Model Membranes Studied by Affinity Capillary Electrophoresis. Pharm Res 33, 1175–1181 (2016). https://doi.org/10.1007/s11095-016-1862-z

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  • DOI: https://doi.org/10.1007/s11095-016-1862-z

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