Medium and large scale preparation of Nanostructured Lipid Carriers of asenapine maleate: Quality-by-design based optimization, production, characterization and performance evaluation

Abstract

In the present study, scale-up of preparation of Asenapine maleate (ASPM) loaded Nanostructured lipid carriers (NLCs) to medium as well as the large scale was performed with the aid of Quality-by-Design (QbD) approach. High-pressure homogenization (HPH) was used to scale up the ASPM loaded NLCs to medium (40 mL) and large-scale (300 mL) batches. The statistical experimental design was employed to optimize the HPH parameters and the results of the design showed that the size of ASPM loaded NLCs decreased with the increase in pressure and number of cycles of HPH. Also, increasing the number of cycles resulted in a slight increase in the %drug entrapped. FTIR and DSC were used to assess the compatibility between drug and excipients. The shape and surface morphology of NLCs studied by Transmission Electron Microscope revealed a spherical shape with an approximate size of less than 100 nm. The cytotoxicity of NLCs using MTT assay in Caco2 cells demonstrated the safety of ASPM-NLCs. Further, in vivo pharmacokinetics and efficacy studies strengthened the applicability of ASPM-NLCs produced at a large scale for further in vivo and clinical environments.