Investigating effect of microemulsion components: In vitro permeation of ketoconazole

Abstract

The purpose of this study was to evaluate the effect of oil, surfactant/co-surfactant mixing ratios and water on the in vitro permeation of ketoconazole (KTZ) applied in O/W microemulsion vehicle through intact rat skin. Lauryl Alcohol (LA) was screened as the oil phase of microemulsions, due to a good solubilizing capacity of the microemulsion system. The pseudo-ternary phase diagrams for microemulsion regions were constructed using LA as the oil, Labrasol (Lab) as the surfactant (S) and ethanol (EtOH) as the cosurfactant (CoS). The formulation which showed a highest permeation rate of 54.65 ± 1.72 µg/cm(2)/h(1) and appropriate physico-chemical properties was optimized as containing 2% KTZ, 10% LA, 20% Lab/EtOH (1:1) and 68% double distilled water (w/w). The efficiency of microemulsion formulation in the topical delivery of KTZ was dependent upon the contents of water and LA as well as Lab/EtOH mixing ratio. It was concluded that the percutaneous absorption of KTZ from microemulsions was enhanced with increasing the LA and water contents, and with decreasing the Lab/EtOH ratio in the formulation. Candida albicans was used as a model fungus to evaluate the antifungal activity of the best formula achieved, which showed the widest zone of inhibition as compared to KTZ reference. The studied microemulsion formulation showed a good stability for a period of three months. Histopathological investigation of rat skin revealed the safety of microemulsion formulations for topical use. These results indicate that the studied microemulsion formulation might be a promising vehicle for topical delivery of KTZ.

Novel isotretinoin microemulsion-based gel for targeted topical therapy of acne: formulation consideration, skin retention and skin irritation studies

“…The electric conductivity of ME was measured using a conductivity meter (EquipTronics, EQ-664, Mumbai, India) equipped with an inbuilt magnetic stirrer. The viscosity of ME was measured using a Brookfield Viscometer LVDV-IIIU (Brookfield Engineering LABS, Stoughton, USA) with spindle SC 18 at 100 rpm using an interval of 30 s. A rheological study of the MBG was performed using a viscometer with Helipath stand (Patel et al 2009(Patel et al , 2011b(Patel et al , 2013a.…”

“…Spontaneous formation of ME was evaluated by the addition of a known amount of water at once to a known amount of oil, emulsifier and co-emulsifier with controlled stirring. The ease of formation of clear ME was taken as the criteria of spontaneity of microemulsification (Patel et al 2009(Patel et al , 2011b(Patel et al , 2013a.…”

“…After hair was shaved carefully with an electric clipper, the skin was excised from the abdominal region of each killed rat and the subcutaneous fat and other extraneous tissues were removed without damaging the epidermal surface. The excised rat skins were rinsed with physiological saline and the thickness of each skin tissue was kept almost similar (Patel et al 2009(Patel et al , 2011b). …”

“…The permeation rate of ITTN at steady state (J ss , lg/cm 2 /h) through rat skin was calculated from the slope of the linear portion of the cumulative amount that permeated through the rat skins per unit area versus time plot. To obtain the permeability coefficient K p (cm/h), the following equation was used: K p = J ss /C 0 (Patel et al 2009(Patel et al , 2011b.…”

“…In comparison, the novel drug delivery systems of recently available anti-acne formulations have potential to reduce the adverse effects without reducing the efficacy. Microemulsion (ME) offers a powerful way for drug delivery as colloidal drug carrier, due to its versatility and favorable advantages (Bachhav and Patravale 2009;Djordjevic 2004;Patel et al 2009Patel et al , 2011bPatel et al , 2013a. The application of ME systems to skin distributes the anti-acne agent(s) steadily and reduce irritation.…”