Development of Functional Microemulsions for Brain Uptake in Neurodegenerative Disorders

Abstract

The objective of this research project was to demonstrate the enhanced drug uptake in brain followed by oral administration of functional microemulsions. The oils like turmeric oil (TO) and rosemary oil (RO) were screened on the basis of literature and were formulated in water in oil microemulsions (ME) containing functional components. Initially, preformulation studies were performed for screening and selection of functional components. Based on comprehensive results of solubility study and emulsification study Kolliphor RH40 was selected as surfactant (S) and Ethanol and Transcutol P were selected as co-surfactants (CoS)/co-solvents for TO-ME and RO-ME respectively. Further, the ratio of S:CoS was finalized using construction of pseudo ternary phase diagrams as 2:1 w/w. Using the selected components at fixed composition of Smix, formulations were optimized using Extreme lattice mixture design using Minitab software and validated experimentally. In vitro characterization revealed clear, transparent yellow colored formulations with globule size less than 100 nm and negative zeta potential. The formulations were found stable on dilution and centrifugation. In vitro drug release showed 3.60 and 4.06-fold improvement in drug release for CUR-TO-ME and CUR-RO-ME respectively when compared to CUR Solution. Accelerated stability studies showed good stability of formulations exhibiting greater than 90% of drug remained with globule size less than 50 nm at the end of 6 months. The ex vivo permeation study revealed 2.38 and 2.23-fold improvement in cumulative drug release whereas 2.41 and 2.25-fold improvement in steady state flux for CUR-TO-ME and CUR-RO-ME respectively. Preliminary in vivo brain pharmacokinetics in adult zebrafish revealed 3.41 and 2.86-fold enhancement in Cmax and 3.97 and 1.88-fold improvement in AUC for CUR-TO-ME and CUR-RO-ME respectively.