FORMULATION AND OPTIMIZATION BY APPLYING 32 FULL FACTORIAL DESIGN OF MUCOADHESIVE MICROSPHERES OF NIFEDIPINE
Objective: The purpose of this research work is to formulate and optimize mucoadhesive microspheres of nifedipine using Carbopol 934P as mucoadhesive and ethyl cellulose as a carrier polymer for controlling the release of nifedipine.
Methods: The emulsion solvent evaporation technique was used for the preparation of microspheres and the 32 full factorial designs were employed for optimization of microspheres. The developed microspheres were characterized for percent yield, entrapment efficiency, particle size, in vitro release study, percent mucoadhesion, surface morphology, and stability study.
Results: Evaluating outcomes of preliminary batches indicated that 100 ml volume of processing medium, 5 h stirring time and 2% concentration of emulsifying agent were suitable for spherical, free-flowing microspheres and high percentage drug entrapment efficiency. The optimized batch exhibited 84.35% drug entrapment efficiency, 61.78% mucoadhesion and drug release were also sustained for more than 12 h. Scanning electron microscopy study revealed that produced microspheres were spherical in shape.
Conclusion: Experimental responses of the optimized batch have close proximity with the predicted value and stability study of the optimized formulation proved the formulation is stable for a long period of time; hence, it is an excellent alternative over the conventional delivery system.
2. Webster LM, Myers JE, Nelson-Piercy C, Harding K, Cruickshank JK, Watt-Coote I. Labetalol versus nifedipine as antihypertensive treatment for chronic hypertension in pregnancy: A randomized controlled trial. Hypertension 2017;70:915-22.
3. Rich S, Brundage BH. High-dose calcium channel-blocking therapy for primary pulmonary hypertension: Evidence for long-term reduction in pulmonary arterial pressure and regression of right ventricular hypertrophy. Circulation 1987;76:135-41.
4. Panchagnula R, Singh R, Ashokraj Y. In vitro evaluation of modified release formulations of nifedipine from Indian market. Ind J Pharm Sci 2007;69:556-61.
5. Wu J, Wang B, Wei C, Bu F, Guo R. Pharmacokinetics of nifedipine sustained-release tablets in healthy Chinese volunteers. J Chin Pharm Sci 2007;16:192-6.
6. Radha G, Samantha L, Swetha Y, Praveen K. Formulation and in vitro evaluation of mucoadhesive microspheres of nifedipine. J Pharm Scientific Innov 2012;1:39-43.
7. Beri CL, Sood R, Hemraj, Gupta A. Stomach specific mucoadhesive microspheres as controlled drug delivery system – A review. Int J Pharm Pharm Sci 2013;5:21-6.
8. Kadam N, Suvarna V. Microsphere: A brief review. Asian J Bio Pharm Sci 2015;5:13-9.
9. Andrews GP, Laverty TP, Jones DS. Mucoadhesive polymeric platforms for controlled drug delivery. Eur J Pharm Biopharm 2009;71:505-18.
10. Serra L, Doménech J, Peppas NA. Engineering design and molecular dynamics of mucoadhesive drug delivery systems as targeting agents. Eur J Pharm Biopharm 2009;71:519-28.
11. Chowdary KP, Devi GS. Preparation and evaluation of mucoadhesive microspheres of efavirenz for enhancing its dissolution rate and bioavailability. Res J Pharm Bio Chem Sci 2012;3:119-24.
12. Bardonnet PL, Faivre V, Pugh WJ, Piffaretti JC, Falson F. Gastroretentive dosage forms: Overview and special case of Helicobacter pylori. J Control Release 2006;111:1-8.
13. Smart JD. The basics and underlying mechanisms of mucoadhesion. Adv Drug Deliv Rev 2005;57:1556-68.
14. Mule MS, Kshirsagar RV. Gastroretentive mucoadhesive microsphere: A review. Indo Am J Pharm Res 2011;1:483-505.
15. Jadhav SA, Sharma Y. Mucoadhesive microsphere. Indo Am J Pharm Res 2015;5:3459-70.
16. Yadav VK, Kumar B, Prajapati S, Shafaat K. Design and evaluation of mucoadhesive microspheres of repaglinide for oral controlled release. Int J Drug Dev 2011;3:357-70.
17. Bashir S, Asad M, Qamar S, Hassnain F, Karim S, Nazir I. Development of sustained-release microbeads of nifedipine and in vitro characterization. Trop J Pharm Res 2014;13:505-10.
18. Desai S, Vidyasagar G, Shah V, Desai D. Preparation and in vitro characterization of mucoadhesive microspheres of midazolam: Nose to brain administration. Asian J Pharm Clin Res 2011;4:100-2.
19. Khan AB, Thakur RS. Formulation and evaluation of mucoadhesive microspheres of tenofovir disoproxil fumarate for intravaginal use. Curr Drug Deliv 2014;11:112-22.
20. Khan R, Prajapati S, Irchhiaya R, Singh G. Formulation and evaluation of mucoadhesive microspheres of flurbiprofe. Pharmacologyonline 2010; 4:1560-6.
21. Garg R, Gupta GD. Gastroretentive floating microspheres of silymarin: Preparation and in vitro evaluation. Trop J Pharm Res 2010;9:59-66.
22. Deshmukh MT, Mohite SK. Formulation and characterization of olanzepine-loaded mucoadhesive microspheres. Asian J Pharm Clin Res 2017;4:249-55.
23. Velmurugan S, Ali MA. Development and evaluation of ritonavir mucoadhesive microspheres. Asian J Pharm Clin Res 2014;5:47-52.
24. Singh B, Kaur T, Singh S. Correction of raw dissolution data for loss of drug and volume during sampling. Indian J Pharm Sci 1997;59:196-9.
25. Sabiu S, Garuba T, Sunmonu T, Ajani E, Sulyman A, Nurain I, et al. Indomethacin-induced gastric ulceration in rats: Protective roles of Spondias mombin and Ficus exasperata. Toxicol Rep 2015;2:261-7.
26. Lehr CM, Bouwstra JA, Tukker JJ, Junginger HE. Intestinal transit of bioadhesive microspheres in an in situ loop in the rat – A comparative study with copolymers and blends based on poly (acrylic acid). J Control Release 1990;13:51-62.
27. Hardenia SS, Jain A, Patel R, Kaushal A. Formulation and evaluation of mucoadhesive microspheres of ciprofloxacin. J Adv Pharm Edu Res 2011; 1:214-24.
28. Ararath D, Velmurugan S. Formulation and evaluation of nevirapine mucoadhesive microspheres. Int J Pharm Pharm Sci 2015;7:342-8.
29. Dey S, Pramanik S, Malgope A. Formulation and optimization of sustained release stavudine microspheres using response surface methodology. ISRN Pharm 2011;2011:627623.
30. Sawant K, Patel M, Patel J, Mundada P. Formulation, optimization, characterization and in vivo anti-ulcer activity of esomeprazole magnesium trihydrate gastroresistant microspheres Int J Pharm Pharm Sci 2017;9:273-82.
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