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Interaction of Surface Active Drug Promethazine Hydrochloride with Surfactants: Drug Release from Microemulsions

Wechselwirkung des oberflächenaktiven Wirkstoffs Promethazinhydrochlorid mit Tensiden: Wirkstofffreisetzung aus Mikroemulsionen
  • Manoni Kurtanidze

    Dr. Manoni Kurtanidze received her Ph. D. degree in 2019 from Tbilisi State University. Her research interest is physicochemical behavior of micellar solutions, study of the properties of water aggregates directly at the polar heads without an interface.

    , Tinatin Butkhuzi

    Dr.Tinatin Butkhuzi was awarded her PhD degree in Chemistry in 2015 from Tbilisi State University. Her research interests covers investigation of structural changes of water nanodroplets confined in reverse micelles and microemusion drug delivery.

    , Irma Tikanadze

    Irma Tikanadze is PhD student in colloid chemistry since 2016 and works on her doctoral thesis about the conductivity of reverse microemulsions.

    , Rusudan Chaladze

    Rusudan Chaladze is currently a PhD student and works on her doctoral thesis about of mixed microemulsions and their application in liquid chromatography.

    , Manuchar Gvaramia

    Dr. Manuchar Gvaramia was awarded his PhD degree in Chemistry in 2018 from Ivane Javakhishvili Tbilisi State University. He is now postdoctoral scientist at the University of Geneva, Laboratory of colloid and surface chemistry. His interests focuses on fundamental physical and analytical chemistry of colloids and surfaces.

    , Ketevan Nanobashvili

    Ketevan Nanobashvili graduated from Ivane Javakhishvili Tbilisi State University in 2020 with master degree in physical chemistry. Since 2020 she is PhD student in colloid chemistry and works on her doctoral thesis about thermodynamics of micellization processes.

    , Maka Alexishvili

    Dr. Maka Alexishvili received her PhD degree at Moscow Institute of Chemistry Synthesis in1975. She was working as Docent at the Department of Physical Chemistry of Tbilisi State University during 1977-2006. Since 2017 she is invited lecturer at Tbilisi State Medical University. Her research interests are thermodynamics, chemical kinetics and pharmacokinetics of surface active drugs.

    , Polina Toidze

    Polina Toidze defended her PhD at Georgian Technical University in 2019. Theme of her Doctoral Thesis was “The influence of the Chemical Composition and Structure of Nanocomposites on the Properties of a Hybrid Catalyst”. She is working as researcher at Georgian Technical University, Department of Chemical and Biological Engineering from 2002 to the present. Since 2017 to the present she is specialist at Research Institute of Green and Sustainable Chemistry.

    and Marina Rukhadze

    Prof. Marina Rukhadze received her PhD and Doctor of Science degrees in 1989 and 1999 respectively from Tbilisi State University. Her major research interests include the microemulsions, structure of the confined water, reverse micelles, cloud-point extraction, surface active drugs, biosurfactants, periodic reactions in gels, etc.

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Abstract

The interaction of surface-active drugs with surfactants, used in the simulation of artificial membranes by direct and reversed micelles, mainly determines the transport of drugs in the body and the complex process of the binding to receptors. Besides, the delivery of drugs into the body via microemulsions has been successfully used to reduce the first-pass metabolism. The structure of mixed reverse microemulsions based on the ionic surfactant sodium bis(2-ethylhexyl)sulfosuccinate (AOT) and the cationic surface active drug promethazine hydrochloride (PMT) was studied spectroscopically in the infrared and UV-visible regions, as well as using electrical conductivity and dynamic light scattering. The release profile of PMT from AOT-based microemulsions was studied using cellulose dialysis bags. The introduction of PMT additive into the water pockets of reverse AOT micelles leads to: a) an increase in free water fraction and a decrease in bound water fraction; b) changing the chromatographic retention factors of the model compounds; c) insignificant influence on the values of the binding constant of optical probe o-nitroaniline with the head groups of AOT; d) quenching of water-induced percolation in electrical conductance of reverse AOT microemulsions; e) a slight decrease in the size of water droplets at the same values of the molar ratio of water/surfactant. The release of PMT from the aqueous system obeys Fick’s law of diffusion (n = 0.4852), and the release of PMT from microemulsions is based on non-Fickian or anomalous diffusion.

Zusammenfassung

Die Wechselwirkung von oberflächenaktiven Arzneimitteln mit Tensiden, die bei der Simulation künstlicher Membranen durch direkte und umgekehrte Mizellen verwendet wurden, bestimmt hauptsächlich den Transport von Arzneimitteln im Körper und den komplexen Prozess ihrer Bindung an Rezeptoren. Außerdem wurde die Abgabe von Arzneimitteln in den Körper durch Mikroemulsionen erfolgreich für die Reduzierung des First-Pass-Metabolismus verwendet. Die Struktur von gemischten Umkehrmikroemulsionen auf der Basis des ionischen Tensids Natrium-bis-(2-ethylhexyl)-sulfosuccinat (AOT) und des kationischen oberflächenaktiven Arzneimittels Promethazinhydrochlorid (PMT) wurde spektroskopisch im infraroten und UV-sichtbaren Bereich sowie mit Methoden der elektrische Leitfähigkeit und dynamische Lichtstreuung untersucht. Das Freisetzungsprofil von PMT aus AOT-basierten Mikroemulsionen wurde unter Verwendung von Cellulosedialysebeuteln untersucht. Die Einführung von PMT-Additiven in die Wassertaschen von AOT-Umkehrmizellen führt zu: a) einer Zunahme der freien Wasserfraktion und einer Abnahme der gebundenen Wasserfraktion; b) einer Änderung der chromatographischen Retentionsfaktoren der Modellverbindungen; c) einen unbedeutenden Einfluss auf die Werte der Bindungskonstante der optischen Sonde o-Nitroanilin mit den Kopfgruppen von AOT; d) dem Löschen der wasserinduzierten Perkolation in der elektrischen Leitfähigkeit von umgekehrten AOT-Mikroemulsionen; e) einer leichten Abnahme der Größe der Wassertröpfchen bei den gleichen Werten des Molverhältnisses von Wasser/Tensid. Die Freisetzung von PMT aus dem wässrigen System folgt dem Fick‘schen Diffusionsgesetz (n = 0,4852), und die Freisetzung von PMT aus Mikroemulsionen basiert auf einer nicht-Fick‘schen oder anomalen Diffusion.


Prof. Marina Rukhadze 3, I.Chavchavadze ave Tbilisi, 0179 Georgia Tel.: +995 599 19 75 25

About the authors

Dr. Manoni Kurtanidze

Dr. Manoni Kurtanidze received her Ph. D. degree in 2019 from Tbilisi State University. Her research interest is physicochemical behavior of micellar solutions, study of the properties of water aggregates directly at the polar heads without an interface.

Dr. Tinatin Butkhuzi

Dr.Tinatin Butkhuzi was awarded her PhD degree in Chemistry in 2015 from Tbilisi State University. Her research interests covers investigation of structural changes of water nanodroplets confined in reverse micelles and microemusion drug delivery.

Irma Tikanadze

Irma Tikanadze is PhD student in colloid chemistry since 2016 and works on her doctoral thesis about the conductivity of reverse microemulsions.

Rusudan Chaladze

Rusudan Chaladze is currently a PhD student and works on her doctoral thesis about of mixed microemulsions and their application in liquid chromatography.

Dr. Manuchar Gvaramia

Dr. Manuchar Gvaramia was awarded his PhD degree in Chemistry in 2018 from Ivane Javakhishvili Tbilisi State University. He is now postdoctoral scientist at the University of Geneva, Laboratory of colloid and surface chemistry. His interests focuses on fundamental physical and analytical chemistry of colloids and surfaces.

Ketevan Nanobashvili

Ketevan Nanobashvili graduated from Ivane Javakhishvili Tbilisi State University in 2020 with master degree in physical chemistry. Since 2020 she is PhD student in colloid chemistry and works on her doctoral thesis about thermodynamics of micellization processes.

Dr. Maka Alexishvili

Dr. Maka Alexishvili received her PhD degree at Moscow Institute of Chemistry Synthesis in1975. She was working as Docent at the Department of Physical Chemistry of Tbilisi State University during 1977-2006. Since 2017 she is invited lecturer at Tbilisi State Medical University. Her research interests are thermodynamics, chemical kinetics and pharmacokinetics of surface active drugs.

Polina Toidze

Polina Toidze defended her PhD at Georgian Technical University in 2019. Theme of her Doctoral Thesis was “The influence of the Chemical Composition and Structure of Nanocomposites on the Properties of a Hybrid Catalyst”. She is working as researcher at Georgian Technical University, Department of Chemical and Biological Engineering from 2002 to the present. Since 2017 to the present she is specialist at Research Institute of Green and Sustainable Chemistry.

Prof. Marina Rukhadze

Prof. Marina Rukhadze received her PhD and Doctor of Science degrees in 1989 and 1999 respectively from Tbilisi State University. Her major research interests include the microemulsions, structure of the confined water, reverse micelles, cloud-point extraction, surface active drugs, biosurfactants, periodic reactions in gels, etc.

Acknowledgements

This work was supported by Shota Rustaveli National Science Foundation of Georgia (SRNSFG) [YS-18-1940].

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Received: 2021-01-31
Accepted: 2021-06-18
Published Online: 2021-09-25
Published in Print: 2021-09-30

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