OPTIMIZATION OF FORMULATION PARAMETERS OF EMTRICITABINE LOADED N-PALMITOYL GLUCOSAMINE NIOSOMES FOR BRAIN TARGETED DRUG DELIVERY

Emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI) used for the treatment of Human Immunodeficiency Virus (HIV) infection in adults and children. It is an intermediate central nervous system (CNS) penetrating drug with CNS Penetration–Effectiveness score of 0.5. The HIV replication at sub therapeutic concentrations of the drug in the cerebrospinal fluid (CSF) leads to HIV associated neurocognitive disorders in AIDS patients. The use of glucose analogues as carriers for brain targeting has been widely investigated. Emtricitabine encapsulated niosomes were prepared by four different methods (thin layer evaporation (TLE)-vortex method, thin layer evaporation (TLE)-paddle stirring method, reverse phase evaporation method and proniosome method) with Span 40 and Span 60 as main surfactant. Cholesterol (CHL) and Solulan C24 (SOL) were also included in the niosomal formulations. Variations in compositions of the surfactant or surfactant-lipid mixture were made by varying the molar ratios of Span:CHL:SOL as 100:0:0 and 50:40:10. The total concentration of components ranged from 0.1 to 38 mM. The formulations were size reduced by sonication and size extrusion methods. The formulations were optimized for the method of preparation, concentrations and type of surfactant, total concentration of surfactant, hydration temperature and method of size reduction. The results showed that thin layer evaporation (TLE)-vortex method and thin layer evaporation (TLE)-paddle stirring method as efficient methods. The ratio of Span:CHL:SOL as 50:40:10, the total concentration of the surfactants to be 39 mM, sonication as the efficient method of size reduction and the hydration temperature as 650C. The optimized parameters were used for the preparation of Emtricitabine loaded N-palmitoyl glucosamine (NPG) niosomal preparations with Span 60 and Span 40 with the ratio of Span:CHL:SOL:NPG as 50:40:10:10. The niosomal suspensions were characterized for mean particle size, formation of vesicles, encapsulation efficiency (size exclusion chromatographic method and dialysis method) and evaluated for stability studies. The niosomal formulations were found to be stable at 40C and 250C for a period of 6 months. The formulation containing Span 60 was found to be the best formulation with good percentage entrapment.