Formulation by Design (FbD) approach to develop Tenofovir Disoproxil Fumarate loaded Nanostructured Lipid Carriers (NLCs) for the aptness of nose to brain delivery

Abstract

The objective of the present investigation was to optimize and develop Tenofovir Disoproxil Fumarate (TDF) loaded Nanostrucrured Lipid Carriers (NLCs) with Compritol 888 ATO as solid lipid and oleic acid as liquid lipid by modified emulsion solvent diffusion method using Central Composite design (CCD). Three independent variables viz., Lipid to Drug ratio (A), Aqueous phase pH (B) and Sonication time (min) (C) were taken to investigate their effect on dependent variables viz., particle size (nm) (R1), PDI (R2) and % Entrapment Efficiency (%EE) (R3). Optimized formula of NLC was selected from the design space which was further optimized by changing the surfactants quantity. NLCs were evaluated for physicochemical, morphological, solid state characterization, and in-vitro dissolution in PBS pH 6.4, PBS 7.4 and ACSF. The average particle size was found to be 94.7 ± 15.70 nm with PDI of 0.380 ± 0.024 and 134.3 ± 9.71 nm with PDI of 0.358 ± 0.038 respectively for T4 and T5 NLC formulation. The zeta potential value of -17. ± 3.87 mV and -17.17 ± 1.05 mV and %EE of 35.5 ± 1.04 % and 34.2 ± 2.78 %. Overall, the above finding shows promising results in the area of developing non-invasive intranasal route as an alternative to oral route for brain delivery. 

Keywords: Central composite design, Intranasal, Neuro-AIDS, CNS targeting.