Treatment of non melanoma skin cancer and its precancerous skin lesions is associated with severe
topical and systemic toxicity. So, it has become necessary to develop an efficient novel delivery system with less
side effects and better patient compliance. Topical w/o microemulsion of 5-FU were prepared using sorbitan monooleate
(Span 80), sorbitan trioleate (Span 85), polysorbate 80 (Tween 80), isopropyl alcohol (IPA) with different oils
such as oleic acid, triacetin and isopropyl myristate (IPM). Evaluation tests of microemulsions like determination
of thermodynamic stability, droplet size, viscosity, pH, conductivity and ex vivo release studies were performed.
Spherical shape and Droplet size of microemulsion, which was around 100nm, was supported by Transmission
electron microscopy. The lesser flux across skin for all microemulsion batches and higher skin retention of 5-FU
loaded in microemulsion in comparison to topical 5-FU marketed cream resulted in better control over the drug
release. Skin irritation studies on rats were performed to evaluate chronic toxicity of optimized microemulsion
formulation on skin for 21 days and were compared with control group. Formalin (0.8%) was taken as standard irritant. Rat skin was
observed for erythema and edema and the formulation was found safe for chronic use (p˃0.01). Histopathology studies showed the
epidermal and dermal layers to be normal, showing the 5-FU microemulsion formulation to be safe for topical use. Better control of the
drug release through skin can curtail topical and systemic toxicity which is supported by the skin irritation and histopathology studies.