Intranasal delivery of venlafaxine loaded nanostructured lipid carrier: Risk assessment and QbD based optimization

The objective of the present investigation was to optimize and develop venlafaxine (VLF) loaded nanostructured lipid carrier (NLC) using QbD and risk assessment approach. Full factorial 3(2) design was applied using two independent variables viz., X1: Drug to total lipid ratio and X2: Surfactant concentration whereby their effect on dependent variables viz., Y1: Size, Y2: PDI and Y3: %EE was studied. Compritol 888 ATO and Capmul MCM EP showed highest solubility for VLF as solid and liquid lipid respectively which depicted superior miscibility at solid: liquid lipid ratio of 70:30% w/w. VLF NLC were formulated based on optimized formula obtained from design space which gave experimental values for CQA (Size: 77.08 +/- 3.45 nm, PDI: 0.234 +/- 0.062 and %EE: 81.33 +/- 3.05). FTIR, DSC and XRD studies revealed formation of less ordered crystalline structure of lipid matrix favouring higher encapsulation of VLF. Ex-vivo diffusion study showed higher flux value with VLF NLC (14.2 +/- 0.40 mu g/cm(2)/h) in comparison to VLF solution (9.62 +/- 0.59 mu g/cm(2)/h) across goat nasal mucosa. VLF NLC did not show toxicity and nasal mucosa was intact indicating safety for intranasal administration. Overall, QbD approach sounds to be apt for the successful development of VLF NLC. (C) 2016 Elsevier B.V. All rights reserved.