Master of Science (Research)
School of Biological Sciences
Zhang, Fanyu, Development and Evaluation of Novel Biocompatible Microemulsion Formulations for Transdermal Drug Delivery, Master of Science (Research) thesis, School of Biological Sciences, University of Wollongong, 2016. http://ro.uow.edu.au/theses/4962
Transdermal drug delivery is a noninvasive delivery method which can have numerous advantages for patients. It bypasses first-pass metabolism and can produce a constant and sustained delivery flux when compared to other drug delivery pathways (i.e. oral and injection). To effectively achieve those requirements, microemulsion (ME) formulations have been used as the drug delivery vehicles because they can form spontaneously, are thermodynamically stable and possess high solubilization capacity for drug compounds. This project optimized the composition of topical biocompatible ME formulations and evaluated their transdermal permeation capacity.
In this study, medium chain monoglycerides (MCM) was found can act as the transdermal permeation enhancer in ME formulations. The transdermal permeation rate of sodium fluorescein (NaFlu) produced by both MCM alone and MCM incorporate with surfactant mixture (Tw/Sp) were significantly higher (over 30 and 25-fold, respectively) than that produced by phosphate buffered saline (PBS). Additionally, increasing concentration of MCM leads to an increasing monophasic region (AT) from 15.2% to 33.2% of pseudo-ternary phase diagrams. When incorporated with MCM, it is observed that ethanol (EtOH) largely expanded the AT of pseudo-ternary phase diagrams to 52.3% and effectively improved the transdermal delivery rate of ME formulations. The transdermal delivery rate of different surfactants composed with MCM and EtOH based ME formulations was tested in vitro through hairless mice skin. Both ME formulation contained surfactant BRIJ O10 and Tween 80 presented great permeation performance (over 33 and 29-fold, respectively) when comparing with PBS in delivery of NaFlu. Besides, either surfactant BRIJ O10, Tween 80 or Kolliphor EL showed great results of gentamicin permeation performance (over 10, 13 and 14-fold, respectively) than in PBS when composed with MCM and EtOH based ME formulations. Therefore, ME formulation contains Tween 80 (ME_T8) was selected to assess the bio-distribution of gentamicin in vivo. Results showed that the gentamicin can’t go through mouse skin when dissolved in the PBS treatment. It is found that formulation ME_T8 did facilitate the transdermal delivery of gentamicin through mouse skin to produce detectable systemic drug levels. Furthermore, it is observed that the cumulative amounts of gentamicin in the kidney increasing 2.3-fold when double dose gentamicin was applied in comparison with the single dose ME treatment. These findings indicate monoglyceride-based MEs can act as transdermal drug delivery vehicles with tunable skin permeation characteristics.