Solid Lipid Nanoparticles for Topical Delivery of Acitretin for the Treatment of Psoriasis by Design of Experiment

Abstract

The main objective for this investigation is to develop and optimize the solid lipid nanoparticles formulation of acitretin for the effective drug delivery. Acitretin loaded SLNs were prepared by hot homogenization followed by the ultrasonication using Taguchi’s orthogonal array with eight parameters that could affect the particle size and entrapment efficiency. Based on the results from the analyses of the responses obtained from Taguchi design, three different independent variables including surfactant concentration (%), lipid to drug ratio (w/w) and sonication time (s) were selected for further investigation using central composite design. The lipid Dynasan-116, surfactant poloxomer-188 and co surfactant egg lecithin resulted in better percent drug loading and evaluated for particle size, zeta potential, drug entrapment efficiency, in vitro drug release and stability. All parameters were found to be in an acceptable range. TEM analysis has demonstrated the presence of individual nanoparticles in spherical shape and the results were compatible with particle size measurements. In vitro drug release of optimized SLN formulation (F2) was found to be 95.63 ± 1.52%, whereas pure drug release was 30.12 after 60 min and the major mechanism of drug release follows first order kinetics release data for optimized formulation (F2) with non-Fickian (anomalous) with a strong correlation coefficient (R2 = 0.94572) of Korsemeyer-Peppas model. The total drug content of acitretin gel formulation was found to 99.86 ± 0.012% and the diameter of gel formulation was 6.9 ± 0.021 cm and that of marketed gel was found to be 5.7 ± 0.06 cm, indicating better spreadability of SLN based gel formulation. The viscosity of gel formulation at 5 rpm was found to be 6.1 x 103 ± 0.4 x 103 cp. The release rate (flux) of acitretin across the membrane and excised skin differs significantly, which indicates about the barrier properties of skin. The flux value for SLN based gel formulation (182.754 ± 3.126 μg cm−2 h−1) was found to be higher than that for marketed gel (122.345 ± 4.786 μg cm−2 h−1). The higher flux and Kp values of SLN based gel suggest that it might be able to enter the skin easily as compared with marketed gel with an advantage of low interfacial tension of the emulsifier film that ensures an excellent contact to the skin. This topically oriented SLN based gel formulation could be useful in providing site-specific dermal treatment of psoriasis