Non–melanoma skin cancer (NMSC) is the most common human malignancy and it is estimated
that over 1.3 million cases are diagnosed each year in the United States (Neville et al.,
2007:462). There are three main types of NMSC, which include basal–cell carcinoma (BCC),
squamous–cell carcinoma (SCC) and cutaneous malignant melanoma (CMM). Exposure to
ultra–violet (UV) radiation plays a major role in the aetiology of these three skin cancer types
(Franceschi et al., 1996:24).
5–Fluorouracil is an antineoplastic pyrimidine analogue that functions as an anti–metabolite. It
interferes with DNA (deoxyribonucleic acid), and to a lesser extent, with RNA (ribonucleic acid)
synthesis by blocking the methylation of deoxyuridylic acid into thymidylic acid. It is used in
topical preparations for the treatment of actinic keratosis (AK) and NMSC. The cure rate with
topical 5–fluorouracil is partly reflected by the degree of erythema, erosions, and eventual
crusting which develop at the sites of treatment. This reaction often attains the best clinical
response, but in turn, frustrates patients, which may lead to patient incompliance (McGillis &
Fein, 2004:175). Due to the hydrophilic nature of 5–fluorouracil, the transdermal permeation
through the lipophilic stratum corneum is very low and trivial (Singh et al., 2005:99).
Transdermal drug delivery is the delivery of a chemical substance across the skin to reach the
systemic circulation (Prausnitz et al., 2004:115). This unique drug transport mechanism
suggests many advantages that include safety, patient compliance, user–friendliness, efficiency
and non–invasiveness (Fang et al., 2004:241). The stratum corneum is a specialised structure
that forms part of several anatomically distinct layers of the skin. Seeing that it is the outermost
layer, it provides protection to the skin. It is known as the main barrier to percutaneous
absorption of compounds, as well as water loss, through the skin (Bouwstra et al., 2003:4).
This study focussed on the formulation of six different types of semisolid formulations,
containing 0.5% 5–fluorouracil. The formulations included: a cream, Pheroid cream, emulgel,
Pheroid emulgel, lotion and Pheroid lotion. Pheroid refers to a delivery system which
was incorporated in the formulations in an attempt to enhance the penetration of 5–fluorouracil
into the skin. This drug delivery system consists of unique and stable lipid–based submicronand
micron–sized structures, formulated in an emulsion. The dispersed Pheroid structures
largely comprise of natural essential fatty acids, which have an affinity for the cell membranes of
the human body (Grobler et al., 2008:284–285).
These formulations were manufactured in large quantities and stored at three different temperatures, each with their respective relative humidity (RH): 25 °C/60% RH, 30 °C/60% RH
and 40 °C/70% RH, for a period of six months. Stability tests were conducted on each of these
formulations on the day of manufacture (month 0), and then after 1, 2, 3 and 6 months. The
tests included: determination of concentration of the analytes (assay) by means of high
performance liquid chromatography (HPLC); determination of zeta–potential and droplet size; pH
measurement; viscosity; mass loss determination; physical appearance; and particle size
distribution.
Franz cell skin diffusion tests were performed with these six 5–fluorouracil containing semisolid
formulations (0.5%), as well as with a 0.5% Pheroid solution, 0.5% non–Pheroid solution. A
5.0% Pheroid solution and a 5.0% non–Pheroid solution were also prepared in order to
compare the skin diffusion test results to a 5.0% commercially available ointment. The data of
the 0.5% formulations and solutions, as well as the 5.0% solutions and commercial ointment,
were statistically compared and those formulations (and solutions) that yielded the best results,
with regard to % diffused, epidermis and dermis concentrations, were identified. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2011.
| Identifer | oai:union.ndltd.org:NWUBOLOKA1/oai:dspace.nwu.ac.za:10394/6977 |
| Date | January 2010 |
| Creators | Vermaas, Monique |
| Publisher | North-West University |
| Source Sets | North-West University |
| Detected Language | English |
| Type | Thesis |
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