PMID- 24316265
OWN - NLM
STAT- MEDLINE
DCOM- 20140912
LR  - 20140121
IS  - 1873-4995 (Electronic)
IS  - 0168-3659 (Linking)
VI  - 174
DP  - 2014 Jan 28
TI  - A study of microemulsions as prolonged-release injectables through in-situ phase 
      transition.
PG  - 188-94
LID - S0168-3659(13)00923-1 [pii]
LID - 10.1016/j.jconrel.2013.11.022 [doi]
AB  - 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 (99m)Tc 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 (99m)Tc in a first-order manner, than CE-ME. The oil poor LC-ME2 had 
      the slowest release with a t1/2 of 77min, 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.
CI  - Copyright (c) 2013 Elsevier B.V. All rights reserved.
FAU - Wu, Zimei
AU  - Wu Z
AD  - School of Pharmacy, The University of Auckland, Auckland, New Zealand. Electronic 
      address: z.wu@auckland.ac.nz.
FAU - Alany, Raid G
AU  - Alany RG
AD  - School of Pharmacy, The University of Auckland, Auckland, New Zealand; School of 
      Pharmacy and Chemistry, Kingston University, London, UK.
FAU - Tawfeek, Noor
AU  - Tawfeek N
AD  - School of Pharmacy, The University of Auckland, Auckland, New Zealand.
FAU - Falconer, James
AU  - Falconer J
AD  - School of Pharmacy, The University of Auckland, Auckland, New Zealand.
FAU - Zhang, Wenli
AU  - Zhang W
AD  - School of Pharmacy, The University of Auckland, Auckland, New Zealand.
FAU - Hassan, Ibrahim M
AU  - Hassan IM
AD  - Auckland Hospital, Auckland, New Zealand.
FAU - Rutland, Michael
AU  - Rutland M
AD  - Auckland Hospital, Auckland, New Zealand.
FAU - Svirskis, Darren
AU  - Svirskis D
AD  - School of Pharmacy, The University of Auckland, Auckland, New Zealand.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131205
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Emulsions)
RN  - 059QF0KO0R (Water)
RN  - 7440-26-8 (Technetium)
SB  - IM
MH  - Animals
MH  - Delayed-Action Preparations
MH  - Drug Delivery Systems
MH  - Emulsions/*administration & dosage/pharmacokinetics
MH  - Injections, Subcutaneous
MH  - Liquid Crystals/chemistry
MH  - Phase Transition
MH  - Rabbits
MH  - Technetium
MH  - Water/chemistry
OTO - NOTNLM
OT  - Gamma-scintigraphy
OT  - Liquid crystal
OT  - Macrogol (15)-hydroxystearate (CID 71311956)
OT  - Microemulsion
OT  - Molybdenum (CID 23932)
OT  - Nile Red (CID 65182)
OT  - Phase transition
OT  - Prolonged drug release
OT  - Sodium pertechnetate ((99m)Tc) (CID 23689036)
OT  - Sorbitan monooleate (CID 9920342)
OT  - Subcutaneous injection
EDAT- 2013/12/10 06:00
MHDA- 2014/09/13 06:00
CRDT- 2013/12/10 06:00
PHST- 2013/10/11 00:00 [received]
PHST- 2013/11/19 00:00 [revised]
PHST- 2013/11/27 00:00 [accepted]
PHST- 2013/12/10 06:00 [entrez]
PHST- 2013/12/10 06:00 [pubmed]
PHST- 2014/09/13 06:00 [medline]
AID - S0168-3659(13)00923-1 [pii]
AID - 10.1016/j.jconrel.2013.11.022 [doi]
PST - ppublish
SO  - J Control Release. 2014 Jan 28;174:188-94. doi: 10.1016/j.jconrel.2013.11.022. 
      Epub 2013 Dec 5.