| Summary: | The skin is the largest and most easily accessible organ of the human body thus making it the ideal
route for systemic drug delivery. The transdermal route of drug delivery offers several advantages
compared to the traditional routes including elimination of first pass metabolism and higher patient
compliance. However, many drugs are topically and systemically ineffective when applied onto the
skin, due to their almost complete failure to penetrate the skin. The main limitation lies in the
stratum corneum, the barrier of the skin, which prevent the drug from reaching the deeper skin strata.
5-Fluorouracil is a polar hydrophilic drug and is therefore not a good penetrant through skin. A
popular technique to increase transdermal permeation is to use a penetration enhancer, which
reversibly reduce the permeability barrier of the stratum corneum. The primary aim of this study
was to determine the effect of Brij 97 in the presence and absence of carrageenan on the transdermal
delivery of 5-fluorouracil.
The formulations were identified by means of confocal laser scanning microscopy and measurement
of the particle size. The zeta-potential was measured to determine whether the formulations were
stable and the pH was measured to determine if the internal structures of the formulations were
affected by the drug. The drug released from the formulations was measured with a VanKel
dissolution apparatus. In vitro transdermal diffusion studies were performed using vertical Franz
diffusion cells with human epidermal skin. Histopathological studies were carried out on human
epidermis skin to determine if the surfactant, Brij 97, had any effect on the skin.
Through confocal laser scanning microscopy and particle size measurements, the 4 and 8% Brij 97
formulations without carrageenan could be identified as emulsions while the 15 and 25% Brij 97
formulations without carrageenan could be identified as microemulsions. The 4, 8, 15 and 25% Brij
97 formulations containing carrageenan could be identified as gels.
The results obtained from the zeta-potential analysis indicated that the 4 and 8% Brij 97 formulations
without carrageenan and 4% Brij 97 formulation with carrageenan are the most electronegative and
thus the most stable. The pH measurements confirmed that the internal structure of the formulations
was not influenced by the drug.
5-Fluorouracil was released from the formulations. The 4 and 8% Brij 97 formulations without
carrageenan had an enhancing effect on the penetration of 5-fluorouracil while the 4, 8, 15 and 25%
Brij 97 formulations with carrageenan and the 15 and 25% Brij 97 formulations without carrageenan
had an hindering effect on the penetration of 5-fluorouracil. Although carrageenan led to good
adhesiveness of the formulation on the skin, it did not lead to the enhancement of the penetration of
5-fluorouracil through the skin.
When histopathological studies were carried out on female human abdominal skin, Brij 97, the
surfactant, was found to have no damaging effect on the skin structure. === Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2006.
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