The skin, by weight, is the largest organ of the body. Human skin serves to provide
several important functions that may be classified. in a general context, as protective,
maintaining homeostasis and sensing. The outermost layer of the skin, the stratum
corneum, has an essential role as a barrier against the transport of water and of chemical
and biological agents.
In this study acyclovir (ACV), an antiviral used for treating the varicella zoster virus, was
used. It is sensible to say that a hydrophilic drug like acyclovir needs a delivery vehicle
or penetration enhancer to permeate the skin with more ease.
In an attempt to enhance the permeation of acyclovir, it was formulated in a delivery
vehicle with the same formulation as for a micro-emulsion. Increasing percentages of the
surfactant, Brij 97, were incorporated in the formulation to determine which of the four
formulations is indeed a micro-emulsion. A gelating agent. carrageenan, was used to
make the emulsion transdermally more applicable; the influence of this component on the
transdermal delivery of acyclovir was also determined.
Therefore the aim of this study was to determine:
-The effect of a drug delivery vehicle on the transdermal delivery of acyclovir;
-The specific formulation of a micro-emulsion and
-The influence of a gelating agent on the transdermal delivery of acyclovir.
Diffusion studies were performed in vertically mounted glass Franz diffusion cells. The
epidermis of female abdominal skin, obtained after abdomeoplasty, was heat separated
from the dermis. One millilitre of emulsion (0.1%: 1mg/ml ACV) was added to the skin
sample in the donor side of the diffusion cell. The control solution had an equivalent
amount of active in water and was added to the donor compartment in a separate
experiment. The receptor phase was PBS (phosphate buffered solution). The entire
receptor phase of the cells was removed every second hour and was replaced with fresh
receptor phase at 37°C. The amount of acyclovir in the receptor phase was determined
by HPLC analysis.
The cumulative amounts of the active that permeated the skin over the 24 hour period
were plotted with the slope of the graphs representing the flux in ng/cm²/h. The average
flux values of the experimental cells and control cells were compared.
Results of the diffusion studies without carrageenan showed that increasing the
concentration of the surfactant increased the diffusion of acyclovir. Permeation studies
with carrageenan had a totally different outcome. The enhancement ratio of the
experimental cells was much lower than that of the control cells. However the
experimental cells showed a small increase as the concentration of the surfactant
increased.
From VanKel dissolution studies it could be seen that release of acyclovir from the
emulsion was not a problem and that the active was available for absorption.
Confocal studies were done to determine whether there were any vesicles in the
emulsions. Vesicles were expected in the 25% Brij 97 emulsion because it was the same
formulation as a micro-emulsion, but vesicles could only be found in the 4% and 8% Brij
97 emulsion.
A previous study with acyclovir and three different delivery vehicles gave enhancement
ratios between 0.32 to 2.92. Values obtained in this study of the 4% and 8% Brij 97
emulsion without carrageenan were more or less the same but the 15% and 25% Brij 97
emulsion had a much higher enhancement ratio. For the emulsions with carrageenan not
one exceeded an enhancement ratio of 0.57.
More studies still have to be done on micro-emulsions to determine which specific
concentration of surfactant forms a micro-emulsion. The active itself and its
physicochemical properties also play an important role in the diffusion studies with the
specific delivery vehicle and further research has to be done with different model drugs. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2006.
| Identifer | oai:union.ndltd.org:NWUBOLOKA1/oai:dspace.nwu.ac.za:10394/956 |
| Date | January 2006 |
| Creators | Roestorf, Maderi |
| Publisher | North-West University |
| Source Sets | North-West University |
| Detected Language | English |
| Type | Thesis |
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