Amorolfine hydrochloride loaded solid lipid nanoparticles: Preparation, characterization and ex vivo nail permeation study to treat onychomycosis.

Abstract

Onychomycosis is a disease of the nail plate caused by fungi, leading to the progressive defacing of the nail. The infection requires a longer period of treatment orally and topically. The treatment with the topical route is difficult due to the low availability of drugs across the infected nail. This failure in topical treatment is the drawback of the conventional drug delivery system (DDS), particularly drug penetration issues across the nail plate. The solid lipid nanoparticle (SLN) approach was used to overcome such issues. The drug amorolfine hydrochloride (AOF) was incorporated into SLN by using the micro-emulsion cold dilution method. Monostrearin and stearic acid were used as solid lipids in the formulation of drug-loaded SLNs. The nanoparticle formulation was optimized by varying the type of solid lipids and bile salts. Sodium taurocholate (STC) and sodium tauroglycholate (STG) are the bile salts used as biosurfactants in the formulation. The SLNs prepared with stearic acid and STG demonstrated higher drug encapsulation efficiency (71.73%) and drug loading efficiency (13.03%) than monostearin. Bile salts have affected the particle size range and STG was found to produce smaller size particles with stearic acid (406nm) than STC. Process parameter homogenization speed was also optimized and 403 relative centrifugal force (RCF) was optimal to produce smaller-size particles (406nm). The drug permeation through the nail plate and anti-fungal studies were also performed for AOF-SLNs loaded cream and marketed cream (Amfocin). The SLNs have improved the permeation (1.63-fold) and anti-fungal activity (2.50-fold) of AOF. Transmission electron microscopy (TEM) images revealed a spherical shape of SLNs with no aggregation. The physical stability was performed and SLNs have higher stability at refrigeration storage. The SLNs were incorporated in cream for the final application for onychomycosis. The analytical method of high-performance liquid chromatography (HPLC) was used for the quantification of AOF in the formulations.