Development and characterization of Solid-SNEDDS formulation of DHA using hydrophilic carrier with improved shelf life, oxidative stability and therapeutic activity

Abstract

Docosahexanoic acid (DHA) is an essential element for proper development of brain and treatment of cognitive disorders. Oily nature, poor water dispersibility, intestinal permeability, organoleptic characteristic of microalgae oil (DHA oil) limits oral delivery and therapeutic performance. An effort has been made to prepare a novel water soluble Solid Self Nano-Emulsifying Drug Delivery System (S-SNEDDS) of DHA oil having improved physical & oxidative stability, bioavailability and therapeutics using spray drying technology. Optimized S-SNEDDS showed small and spherical shape particles with good water dispersibility, oxidative stability and flow properties, ideal for developing solid dosage forms. DSC and XRD studies depicted amorphous nature of S-SNEDDS with complete dispersion of DHA oil in carrier matrix. Cytotoxicity assay showed nontoxic nature of the developed formulation with no change in Transepithelial electrical resistance (TEER) and paracellular permeability of Caco-2 cells. Ex-vivo studies depicted 5 & 2 fold increase in DHA absorption in intestinal permeability and Caco- 2 uptake studies. In vivo pathophysiological role of DHA in preventing cognitive decline was evaluated with Melamine induced cognitive impairment and treatment with S-SNEDDS was found to augment the role of DHA. Thus, S-SNEDDS improved physicochemical properties and is cost effective pharmaceutical approach to increase clinical uses of DHA.