ENHANCEMENT OF AQUEOUS SOLUBILITY OF EZOGABINE: PREPARATION AND CHARACTERIZATION OF EZOGABINE NANOSUSPENSION ANTICIPATED FOR NOSE TO BRAIN TARGETING BY 32 FACTORIAL DESIGN
Pawar Anil R, Choudhari Pravin D, Pawar Amol R
Quality Assurance Department, MES`s, College of Pharmacy, Affiliated to Savitribai Phule Pune University, Sonai, Taluka-Newasa, District-Ahmednagar, Maharashtra, India.
Department of Pharmaceutics, Modern College of Pharmacy, Nigdi, Pune, Maharashtra, India.Research Scholar, PRIST University, Thanjavur, Tamilnadu, India.
Keywords: Ezogabine, Nanosuspension, Nanoprecipitation, Factorial design, Aqueous solubility.
Context:Adverse effects after oral administration, as well as low solubility, present a substantial contest for the suitability of formulations for intranasal drug delivery.
Objectives: The objective of the present work was to develop ezogabine nanosuspension for enhancement of solubility and direct olfactory administration by 32 full factorial design and determine its pharmacokinetic and pharmacodynamic profile in rats.
Methods:The ezogabine nanosuspension was developed by nanoprecipitation-ultrasonication method. The formulation was planned to develop by using a 2-factor, 3-level factorial design. The formulations were subjected to various in-vitro characterizations like particle size analysis, saturation solubility, in-vitro drug diffusion, zeta potential, SEM and TEM. The selected formulation was intranasally instilled into the nostrils of rats with the help of cannula for determining pharmacokinetic and pharmacodynamic profile in-vivo.
Results: The formulation showed better results in terms of in-vitro and in-vivo study. The statistical analysis of data revealed that polymer concentration had significant effect on particle size and no significant effect on saturation solubility and in-vitro drug diffusion. Whereas, ultrasonication time had significant effect on particle size, saturation solubility and in-vitro drug diffusion (solubility). The Cmax revealed concentration of ezogabine in brain and plasma as 0.1812µg/ml and 0.183µg/ml, resp., for plain suspension and concentration of ezogabine in brain and plasma as 0.7885µg/ml and 0.7483µg/ml, resp, for nanosuspension at same dose of 1 mg/ml when administered intranasally.
Conclusion:The present investigation confirmed that the potential of ezogabine nanosuspension for enhancement of aqueous solubility and providing direct nose-to-brain delivery.