Preparation and Characterization of Solid Lipid Nanoparticles (SLNs) Containing Doxepin Hydrochloride To Enhance the Topical Delivery Through Rat Skin

Abstract Eczema is a common skin disease that causes inflammation and itching, significantly affecting a patient’s quality of life. Topical doxepin with antihistamine properties plays an important role in the treatment of eczema. In this study, solid lipid nanoparticles of doxepin were produced and characterized to assess their topical delivery. Box-Behnken and quadratic design models were used to design different formulations. The total surfactant concentration, drug/lipid ratio and Tween/Pluronic ratio were considered as effective factors. Particle size, polydispersity index, zeta potential and percent of EE were investigated. Finally, formulations with the highest drug loading and entrapment efficacy were selected as optimal formulations for further studies such as drug release on cellophane membranes and rat skin. Differential scanning calorimetry and transmission electron microscopy (TEM) were performed on two formulations with desired properties. The results showed the size of the nanoparticles ranged from 180 to 440 nm and the drug encapsulation percentages were between 66% and 82%. TEM images revealed that the SLNs were spherical and round. Investigation on cellophane membrane and rat skin demonstrated the extended drug release and permeation. Moreover, drug accumulation increased by more than three times in the skin. SLN formulations for topical doxepin delivery could increase drug accumulation in the rat skin. This might increase its therapeutic efficiency on itching and reduce systemic side effects by slowing down the rate of skin absorption of doxepin. However, clinical studies are needed to prove these effects in humans.