Abstract
Purpose: Fluoxetine hydrochloride is a selective serotonin reuptake inhibitor, used as an antidepressant. It produces adverse effects on the gastrointestinal tract when administered orally. The objective of this work was to formulate fluoxetine hydrochloride as a microemul-
sion (ME) form for transdermal delivery. Methods: MEs containing fluoxetine hydrochloride were formulated for transdermal drug delivery. The components of these MEs and their concentration ranges were investigated using pseudo-ternary phase diagrams. Characteri-
zation of selected MEs was achieved by pH determination, centrifugation, particle size and viscosity measurements, determination of refractive index and morphology studies using transmission electron microscopy. ME formulations were evaluated in cellulose membrane drug permeation experiments. Selected ME3 was tested for its ability to penetrate through rat skin. Results: ME1 incorporating Tween 80/
n-butanol as surfactant/co-surfactant in the ratio (km) 3:1 was superior to ME2 containing Cremophor RH40/n-butanol surfactant/cosurfac
tant, km=3:1, with regard to drug permeation across a cellulose membrane. Selected ME3 consisting of 5.6% oleic acid, 50% Tween 80/n-butanol (km=3:1), 44.4% water and 4% fluoxetine hydrochloride was stable and exhibited pH, viscosity and particle size properties suitable for successful transdermal drug delivery. This ME exhibited a maximum permeation rate across a cellulose membrane compared with ME4 and ME5 containing 50% Tween 80/n-butanol (km= 3:1) and a higher oil content. Fluoxetine hydrochloride ME3 could permeate through rat skin with an appropriate flux value. Conclusion: ME3 exhibited an optimum composition with regard to stability, pH value, viscosity, droplet size and permeation rate for effective in-vitro delivery across an artificial cellulose membrane, it also exhibited a good penetration ability through rat skin confirming its feasibility as a transdermal delivery system for fluoxetine hydrochloride.
Keywords:
Microemulsions
Fluoxetine hydrochloride
Transdermal delivery
Cellulose membrane permeatio
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