Formulation, Optimization and Evaluation of Self Emulsifying Immediate Release Tablet of Nebivolol HCl using 32Factorial Design
Keywords:
Self micro emulsifying drug delivery system (SMEDDS), Solid self micro emulsifying drug delivery system (SSMEDDS), immediate release self emulsifying tablet (IR-SET), Nebivolol Hydrochloride (NEB), 32 factorial designAbstract
Nebivolol Hydrochloride (NEB) is a lipophilic molecule with low solubility in GI fluid, and high metabolism which leads to its low oral bio availability 12%. The aim of the present investigation was to develop immediate release self emulsifying tablet (IR-SET) as solid SMEDDS to enhance the solubility and permeability of the drug. Solubility study, pseudo-ternary phase diagrams and 32 factorial design were used to select the components of the system and optimize the composition of liquid SMEDDS. Optimal L-SMEDDS contains Kollisolv GTA, Tween 80 and Propylene glycol as oil, surfactant and co-surfactant, respectively in the ratio of 20:26.66:53.34 % w/w, formulates L-SMEDDS with droplet size (55.98 nm), PDI (0.37), emulsification time (16±1.52 sec) and drug content (97.43±0.30 %). The liquid SMEDDS were adsorbed onto Neusilin US2 by adsorbtion technique to form SSMEDDS. DSC and SEM studies suggested that NEB in the S-SMEDDS may be present in the molecular dispersed state and was sufficiently adsorbed onto solid carrier, respectively. S-SMEDDS was compressed into IR-SET by direct compression method and composition of IR-SET was optimized using 32 factorial design. Optimal IR-SET showed disintegration time (92 + 0.57 sec), droplet size (68.57 nm), PDI (0.34) and drug content (96.33±0.15 %). In vitro dissolution studies and ex vivo diffusion studies in rat stomach suggested that SMEDDS played an important role in solubility and permeability enhancing effect. Accelerated stability studies indicated that formulation were stable. Our results illustrated the increase in solubility and permeability of drug from IR-SET.
References
Sikarra D, Shukla V, Kharia AA, Chatterjee DP. Techniques for Solubility Enhancement of Poorly Soluble Drugs: An Overview, Journal of Medical Pharmaceutical and Allied Sciences. 2012; 01: 18-38. 2] Deokate UA, Shinde N, Bhingare U. Novel Approaches for Development and Characterization of SMEDDS: Review, International Journal of Current Pharmaceutical Research. 2013; 5: 7-8. 3] Kamble VA, Jagdale DM, Kadam VJ. Self Micro Emulsifying Drug Delivery System, International Journal of Pharma and Bio Sciences. 2010; V1 (2): 1-9. 4] Qureshi M, Mallikarjun C, Kian W. Enhancement of Solubility and Therapeutic Potential of Poorly Soluble Lovastatin by SMEDDS Formulation Adsorbed on Directly Compressed Spray Dried Magnesium Aluminometasilicate Liquid Loadable Tablets: A Study in Diet Induced hyperlipidemic Rabbits, Asian Journal of Pharmaceutical Sciences. 2014; 1-17. 5] Shah S, Shah M, Agrawal Y. Self- Micro Emulsifying Drug Delivery System: A Novel Approach for Enhancement of Oral Bioavailability of Poorly Soluable Drugs, American Journal of PharmTech Research. 2012; 2(1): 204-215. 6] Koushik Y, Preethi S, Satish P, Shankar MS, Thakur RS. Development of Solid Self Micro Emulsifying Drug Delivery Systems, International Journal of Pharmaceutical Sciences and Nanotechnology. 2013; 6(2): 2014-2021. 7] Kang J, et al. Immediate Release of Ibuprofen from Fujicalin based fast dissolving self emulsifying tablets, Pharmaceutical Technical Newsletters. 2011: 1-3. 8] Zhenghong W, Xiaole Q, Jiayi Q, et al. Solid Self-Micro Emulsifying Dispersible Tablets of Celastrol: Formulation Development, Charaterization and Bioavailability Evaluation, International Journal of Pharmaceutics. 2014; 40-47. 9] www.drugbank.com 10] Narkhede R, Gujar K, Gambhire V. Design and Evaluation of Solid Self-Nanoemulsifying Drug Delivery Systems (S-SNEDDS) for Nebivolol Hydrochloride, International Journal of Institutional Pharmacy and Life Sciences. 2014; 4(2): 224-237. 11] Prajapati ST, Dumaniya SK, Patel CN. Formulation and Evaluation of Self-Nanoemulsifying Powder of Ezetimibe, Journal of Pharmaceutical Science and Drug Designing. 2014; 1(1): 1-8. 12] Gangineni R, Dontha P, Konda SK. Formulation, Characterization and Evaluation of Self Emulsifying Drug Delivery System of Repaglinide, JPR:BioMedRx: An International Journal. 2013; 1(7): 665-672. 13] Patel KB, Patel BK, Enhancement of Oral Bioavailability of Valsartan by using Solid Self Emulsifying Drug Delivery System, International Journal of Universal Pharmacy and Bio Sciences. 2013; 3(3): 141-155. 14] Pimple S, Yeole S, Chaudhari P, Formulation and Evaluation of Self Micro Emulsifying Drug Delivery System for Poorly Water Soluble Drug Risperidone, International Journal of Pharmaceutical Sciences Review and Research. 2013; 23(1): 155-162. 15] Khan F, Islam M, Roni M. Systematic Development of Self-Emulsifying Drug Delivery Systems of Atorvastatin with Improved Bioavailability Potential, Scientia Pharmaceutica. 2012; 80: 1027–1043. 16] Ansari D, Parmar S, Bhadra S. Optimization of Self Micro Emulsifying Delivery System of Clofazimine using Box-Behnken Experimental Design, Pharmagene. 2013; 1(3): 53-61. 17] Bhagwat D, D’Souza J. Formulation and Evaluation of Solid Self Micro Emulsifying Drug Delivery System using Aerosil 200 as Solid Carrier, International Current Pharmaceutical Journal. 2012; 1(12): 414-419. 18] Patil S, Patil V, Shete A, Doijad R. Design, Development and In Vitro Characterization of Self Emulsifying Drug Delivery System for Irbesartan, Iranian Journal of Pharmaceutical Sciences. 2013; 9(2): 67-80. 19] Panner SR, Kulkarni PK. Preparation and statistical optimizationof self nanoemulsifying tablets of Efavirenz using 23 factorial designs, International Journal of Drug Delivery. 2014; 6: 50-57. 20] Lokesh PNV, Abdul AS, Sailaja PB. Design, Development and Formulation of Orodispersible Tablets of a Model Drug Using Response Surface Methodology, Pharmaceutica Analytica Acta. 2012; 3(9): 1-15. 21] Paul Y, Tyagi S, Singh B. Formulation and Evaluation of Oral Dispersible Tablets of Zidovudine with different Superdisintegrants, International Journal of Current Pharmaceutical Review and Research. 2011; 2(2): 81-91. 22] Amrutkar C, Salunkhe K, Chaudari S. Study on Self Nano Emulsifying Drug Delivery System of Poorly Water Soluble Drug Rosuvastatin Calcium, World Journal of Pharmaceutical Research. 2014; 3(4): 2137-2151. 23] Puttachari S, Kalyane NV, Gupta S. Design and Evaluation of Self-Micro Emulsifying Drug Delivery Systems of Acyclovir, International Journal of Pharmacy and Pharmaceutical Sciences. 2014; 6(4): 677-681. 24] Reddy AK, Debnath S, Babu NM. Design Development and Evaluation of Novel Nanoemulsion of Simvastatin, International Journal of Advanced Pharmaceutics. 2013; 3(2): 94-101. 25] Prajapati S, Joshi H, Patel C. Preparation and Characterization of Self-Microemulsifying Drug Delivery System of Olmesartan Medoxomil for Bioavailability Improvement, Journal of Pharmaceutics. 2013; 1-8. 26] Mohd AB, Sanka K, Bandi S, Diwan PV, Shastri N. Solid self-nanoemulsifying drug delivery system (S-SNEDDS) for oral delivery of glimepiride: development and antidiabetic activity in albino rabbits, Drug Delivery.
