The distinctive architecture of the stratum corneum with its unique nature of an
interstitial lipoidal environment plays the major role in regulating the barrier function of
the skin.
The major problem with the transdermal delivery of 5-fluorouracil or idoxuridine is the
permeation of sufficient amounts to the deeper layers of the skin and into the systemic
circulation.
In an attempt to enhance the transdermal permeability of 5-fluorouracil and idoxuridine,
the aim of this study was to evaluate two lamellar gel phase systems (Physiogel
dermaquadrille® and Physiogel NT®) and Emzaloids® as transdermal delivery vehicles
for the two actives. Lamellar gel phase systems (LGPS) and Emzaloids® are both novel
drug delivery systems.
The epidermis of female abdominal skin was used in vertically mounted Franz diffusion
cell experiments. An average amount of 250 mg of the 1% m/m LGPS was applied to
cover the entire diffusion area of 1,075 cm2 of the skin, which contained 2,5 mg of the
active. Samples of the actives in Emzaloids® were prepared and applied in the same way.
The control solutions of the actives in water were prepared so that 1 ml of the applied
solution contained the same amount of drug that was applied to the experimental cells.
The entire receptor phase of the cells was removed at 2,4,6, 8, 10, 12 and 24 hours and
was replaced with fresh 37°C receptor phase. The amount of active in the receptor phase
was determined by HPLC analysis. Graphs of the cumulative amount of the active that
permeated the skin over the 24 hour period were drawn and the slope of the graphs
represented the flux in µg/ml/h. The average flux values of six experimental cells and six
control cells were compared. Entrapment of the actives in the Emzaloid® vesicles was
confirmed with the use of confocal laser scanning microscopy.
Results for the LGPS indicate an enhancement ratio in the order of 4,2 for 5-fluorouracil
and 1,7 for idoxuridine when compared to the control cells. There were no viscosity
changes in the LGPS samples containing 1% m/m of the active when compared with the
blank LGPS samples, suggesting that no change in the internal structure of the LGPS
occurred after the addition of the actives to it. There were also no significant changes in
the pH of the samples.
Entrapment of the actives in the Emzaloid® vesicles occurred readily. The Emzaloid®
vehicle showed a lower rate of release for idoxuridine than the LGPS did during the
VanKel dissolution experiments. This suggests that higher flux values would be obtained
with the LGPS for idoxuridine than with the Emzaloid® formulation, since more drug was
available for permeation through the skin.
This was, however, not the case. The Emzaloid® formulation showed much higher flux
values, showing that even with a smaller amount of active available to permeate the skin
higher flux values were obtained.
Enhancement ratios of 20,33 and 3,50 were achieved with the Emzaloid® formulation for
5-fluorouracil and idoxuridine respectively.
The internal LGPS structure which mimics the skins lipid components remained
unchanged after the addition of the actives. Greater success might be achieved with the
LGPS for different model drugs, since the drugs' physicochemical properties play an
important part in its permeation through the skin.
The Emzaloid® formulation, which is closely related to liposomes and transfersomes,
showed great potential for commercially marketable formulations for the drugs tested but
further research on the formulation has to be done. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2005.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:nwu/oai:dspace.nwu.ac.za:10394/602 |
| Date | January 2004 |
| Creators | Kilian, Dewald |
| Publisher | North-West University |
| Source Sets | South African National ETD Portal |
| Detected Language | English |
| Type | Thesis |
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