Optimization and Characterization Ezogabine-Loaded Nanosuspension for Enhancement of Bioavailability by “Bottom-Up” Technology Using 32 Factorial Design
Ezogabine, an antiepileptic drug used for treating partial epilepsies. It is poorly soluble in water. The dose ranges from 50 mg to 400 mg and the oral bioavailability is 60%. The aim of this research work was to formulate and characterize nanosuspensions of ezogabine with an intention to enhance the oral bioavailability using 32 factorial design. Nanosuspensions were prepared by the “bottom-up” nanoprecipitation method using 32 factorial design and evaluation for particle size, saturation solubility, zeta potential, entrapment efficiency, and in-vitro drug release was done. The FTIR was used to confirm compatibility and to rule out any possible interactions between drug and carriers. The optimal nanosuspension was obtained with particle size of 510.4 nm, saturation solubility of 557 μg/ml, zeta potential of - 4.49 mV, entrapment efficiency of 96.82%, and in-vitro drug release of 100.14%. Also, the optimal formulation was found to be stable in the accelerated conditions. Data of nanosuspensions were fit in to different equations and kinetic models and found to exhibit first order release kinetics with class II transport mechanism of diffusion. The scanning electron microscopy studies showed elongated nanoparticles with porous surface. The “Bottom up” method can be successfully employed to produce ezogabine nanosuspensions achieving reduced particle size and enhancing dissolution rate by increasing the saturation solubility and remained stable at 25 °C.
Keywords: Nanosuspension, saturation solubility, bottom up.
2. Orrin Devinsky, Annamaria Vezzani, Terence J. O’Brien, Nathalie Jette, Ingrid E. Scheffer, Marco de Curtis and Piero Perucca. Epilepsy. Nat Rev Dis Primers 2018; 3:1-24.
3. Judith LZ Weisenberg Michael Wong. Profile of ezogabine and its potential as an adjunctive treatment for patients with partial - onset seizures. Neuropsych Dis Treat 2011; 7:409–14
4. Pawar Anil R, Choudhari Pravin D, Ghule Prashant J, Pawar Amol R and Bankar Prakash V. Study the Effect of Surfactant Concentration and Ultrasonication Time on Aqueous Solubility, Particle Size and In-vitro Drug Diffusion of Ezogabine Nanosuspension by 32 Factorial Designs. Brit Med Bull 2016; 4:15–26.
5. Bhalekar MR, Upadhaya PG, Reddy S, Kshirsagar SJ, Madgulkar AR. Formulation and evaluation of acyclovir nanosuspension for enhancement of oral bioavailability. Asian J Pharm 2014; 8:110-8.
6. Eshagh Esfandi, Vahid Ramezani, Alireza Vatanara, Abdolhossein Rouholamini Najafabadi and Seyyed Pouya Hadipour Moghadda. Clarithromycin Dissolution Enhancement by preparation of Aqueous Nanosuspensions Using Sonoprecipitation Technique. Iran J Pharm Res 2014; 13: 809-18.
7. Shetiya P, Vidyadhara S, Ramu A, Sasidhar RL, Viswanadh K. Development and characterization of a novel nanosuspension based drug delivery system of valsartan: A poorly soluble drug. Asian J Pharm 2015; 9:29-34.
8. Samar A. Afifi, Maha A. Hassan, Ali S. Abdelhameed, and Kadria A. Elkhodairy. Nanosuspension: An Emerging Trend for Bioavailability Enhancement of Etodolac. Int J Polym Sci 2015; 3:1-16.
9. Agarwal V, Bajpai M. Preparation and Optimization of Esomeprazole Nanosuspension using Evaporative Precipitation–Ultrasonication. Trop J Pharm Res 2014; 13:497-503.
10. Robert M Silverstein, Francis X Webster, David J Kiemle. Spectrometric Identification of Organic Compounds. 7th Ed. John Wiley & Sons. Inc. New York. 72 – 126.
11. Ethiraj T, Sujitha R, Ganesan V. Formulation and In-vitro Evaluation of nanosuspension of Glimepiride. Int J Pharmacy 2013; 3:875-82.
12. Sandhya J, Pavani J, Raja Reddy R. Formulation and Evaluation of Nanosuspension of Nisoldipine. Int J Pharm Sci Rev Res 2014; 24:177-81.
13. Pawar Anil R, Choudhari Pravin D, Pawar Amol R. Enhancement of Aqueous Solubility of Ezogabine: Preparation and characterization of Ezogabine nanosuspension anticipated for nose to brain targeting by 32 factorial design. J App Pharm 2016; 8:43-60.
14. Patel DJ, Patel JK, Pandya VM, Jivani RR, Patel RD. Optimization of formulation parameters on famotidine nanosuspension using factorial design and the desirability function. Int J Pharm Tech Res 2010; 2:155-61.
15. Bolmal UB, Manvi FV, Kotha R, Palla SS, Paladugu A, Ramamohan Reddy K. Recent advances in nanosponges as drug delivery system. Int J Pharm Sci Nanotech 2013; 6:1934– 44.
16. Borhade V, Pathak S, Sharma S, Patravale V. Formulation and characterization of atovaquone nanosuspension for improved oral delivery in the treatment of malaria. Future Med 2013.
17. Mudgil M, Pawar PK. Preparation and In Vitro/Ex Vivo Evaluation of Moxifloxacin-Loaded PLGA Nanosuspensions for Ophthalmic Application. Sci Pharm 2013; 81:591–606.
18. Chirumamilla SK, Devi U, Aravally PH, Vuppalapati L, Cherukuri S. Solubility and Dissolution Enhancement of Meropenem by Nano Suspension Approach. J Young Pharm 2017; 9:429-35.
19. Honary S, Zahir F. Effect of Zeta Potential on the Properties of Nano-Drug Delivery Systems - A Review (Part 2). Trop J Pharm Res 2013; 12:265-73.
20. Gera S, Talluri S, Rangaraj N, Sampathi S. Formulation and Evaluation of Naringenin Nanosuspensions for Bioavailability Enhancement. AAPS PharmSci Tech 2017; 18: 3151-62.
21. Devara R., Habibuddin M, Aukunuru J. Enhancement of dissolution rate of poorly soluble drug itraconazole by nanosuspension technology: its preparation and evaluation studies. Asian J Pharm Clin Res 2018; 11:414-21.
22. Kaur J, Bawa P, Yadav SR, Sharma P, Ghai D, Jyoti J, Formulation of curcumin nanosuspension using Box-Behnken design and study of impact of drying techniques on its powder characteristics. Asian J Pharm Clin Res 2017; 10:43-51.
23. Tummala S, Satish Kumar MN, Prakash A. Formulation and in vitro characterization of Carbamazepine polymeric nanoparticles with enhanced solubility and sustained release for the treatment of Epilepsy. Journal of Chemical and Pharmaceutical Research, 2015; 7(2):70-79.
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