Development of a solid supersaturated self-nanoemulsifying preconcentrate (S-superSNEP) of fenofibrate using dimethylacetamide and a novel co-processed excipient

Abstract

Background: Recrystallization of drug and incomplete drug release from liquisolid formulation are two major hurdles in the development of a supersaturated self-nanoemulsifying drug delivery system. The aim of this research work was to develop a solid supersaturated self-nanoemulsifying drug delivery system of fenofibrate (FB) for enhanced dissolution.

Methods: FB loaded supersaturated self-nanoemulsifying preconcentrate (superSNEP) was prepared using dimethyl acetamide (DMA), medium chain triglycerides (MCT), and kolliphor EL. Co-processed excipients (CPE) prepared using inorganic microporous silica (Neusilin US2, Florite 100, or Aerosil 200) and hydrophilic polymers (Polyvinyl alcohol, HPMC, and Kollidon VA64) were evaluated for flow property, BET surface area, and adsorption capacity. Lipophilic fluorescent probe (coumarin-6) was used to investigate the extent of self-emulsification. The formulation was further characterized for solid state, in-vitro cytotoxicity in caco-2 cell line and in-vitro dissolution in a sink and non-sink conditions.

Results: Optimized superSNEP with 20% w/v FB loading spontaneously formed nanoglobules of 40 ± 2.7 nm. DMA based self-nanoemulsifying system was found to be nontoxic to Caco-2 cell even at a very high concentration. CPE prepared using PVA and Florite 100 (1:1 weight ratio) showed the highest adsorption capacity (1 mL/g) and complete release of oil as depicted by fluorescence study. DSC thermogram and PXRD of S-superSNEP confirmed that FB remained in a solubilized state. S-superSNEP showed significantly faster and higher dissolution of FB in sink and non-sink conditions compared to the plain API.

Conclusion: DMA and PVA-F100 based novel co-processed excipient could be potentially useful for the development of solid supersaturated self-nanoemulsifying drug delivery system for enhancing dissolution of lipophilic drugs.

Keywords: Fenofibrate; SNEDDS; co-processed excipient; dimethyl acetamide; solid-SNEDDS; supersaturated self-nanoemulsifying drug delivery system.