A study of microemulsions as prolonged-release injectables through in-situ phase transition

Wu, Zimei, Alany, Raid G., Tawfeek, Noor, Falconer, James, Zhang, Wenli, Hassan, Ibrahim M., Rutland, Michael and Svirskis, Darren (2014) A study of microemulsions as prolonged-release injectables through in-situ phase transition. Journal of Controlled Release, 174 1: 188-194. doi:10.1016/j.jconrel.2013.11.022


Author Wu, Zimei
Alany, Raid G.
Tawfeek, Noor
Falconer, James
Zhang, Wenli
Hassan, Ibrahim M.
Rutland, Michael
Svirskis, Darren
Title A study of microemulsions as prolonged-release injectables through in-situ phase transition
Journal name Journal of Controlled Release   Check publisher's open access policy
ISSN 0168-3659
1873-4995
Publication date 2014-01-28
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.jconrel.2013.11.022
Open Access Status Not Open Access
Volume 174
Issue 1
Start page 188
End page 194
Total pages 7
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Language eng
Subject 3003 Pharmaceutical Science
Abstract Microemulsions (MEs) have been studied extensively as colloidal carriers for the delivery of both water-soluble and lipid-soluble drugs. Our previous study showed that addition of water to ME formulations resulted in phase transition to either liquid crystal (LC) or coarse emulsion (CE). The aim of this study was to investigate whether these MEs could be used as drug delivery vehicles for prolonged release through in-situ phase transition following extravascular injection. Three ME formulations from the same pseudo-ternary phase diagram were investigated with respect to their phase transition behavior, and in-vivo drug release; a coarse emulsion-forming ME (CE-ME), an oil rich LC-forming ME (LC-ME1), and an oil poor LC-forming ME (LC-ME2). CE-ME was a W/O ME and both LC-MEs were O/W type. The release profiles of 99mTc labeled MEs following subcutaneous (SC) injection in rabbits were investigated with gamma-scintigraphy. The CE-ME dispersed readily in water, forming a CE, whereas the LC-forming MEs formed 'depots' in water. Polarized microscopy revealed a LC boundary spontaneously formed at the water/ME interface for the LC-MEs with the LC-ME2 forming a substantially thicker LC layer. The CE resulting from the water-induced transition of the CE-forming ME had a higher viscosity than the MEs, but lower than the LCs resulted from LC-MEs. Compared to LC-ME1, LC-ME2 underwent more rapid phase transition and the resultant LC had significant higher viscosity. The LCs formed from both ME formulations exhibited pseudoplastic properties; increasing the shear rate decreased the apparent viscosity exponentially. Following SC injection into the animal thigh, the LC-MEs had more prolonged release of 99mTc in a first-order manner, than CE-ME. The oil poor LC-ME2 had the slowest release with a t1/2 of 77 min, 2.3 times longer than the oil rich LC-ME1; consistent with the thickness of LC layer formation observed in-vitro and their relative viscosities. In conclusion, the present in-vivo study has demonstrated the application of MEs as extravascular injectable drug delivery systems for sustained release. The retention of the vehicles at the injection site and the release rate were determined predominantly by their phase transition rather than ME type or oil content.
Keyword Gamma-scintigraphy
Liquid crystal
Microemulsion
Phase transition
Prolonged drug release
Subcutaneous injection
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID NZPERF00211
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Pharmacy Publications
 
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