A CONTROLLED RELEASE MICROSPHERE FORMULATION OF AN ANTI-DIABETIC DRUG AND CHARACTERIZATION OF THE MICROSPHERE
Objective: Here the objective of this study was to prepare and characterize sustained release metformin loaded microsphere formulation which was prepared by W1/O/W2 emulsion solvent evaporation technique.
Methods: Guar gum and sodium alginate were used as a matrix building material, whereas ethyl cellulose was applied as a coating polymer. Here various formulations were prepared by changing the drug and guar gum ratio, and the subsequent drug entrapment efficiency (DEE) and drug release were compared and evaluated.
Results: Scanning Electron Microscopy (SEM) studies revealed spherical particles with a smooth appearance. Fourier-transform infrared spectroscopy (FTIR) showed there was no interaction between the ingredients in the final formulation. X-ray Diffraction (XRD) studies showed the emergence of polymorphic forms in the final formulation. The drug entrapment in the final drug loaded microsphere formulations was varied from 30-66.78%. The drug release studies showed the continuous release of the drug through twelve hours. The optimized formulation (f2) found to release 71.5% of drugs at the end of the 12th hour following zero order release kinetics.
Conclusion: The increase in gum concentration in the W1 phase, which enhances viscosity in the W1 phase, resulting in an increase in the drug entrapment up to an optimum level and a decrease in the release rate. So, it can prolong the action. So by using this tool, we can say that metformin loaded microsphere formulation would be a suitable pharmaceutical formulation for the treatment of diabetic patients in modern drug therapy for its prolonged action.Â
2. Beale JM, Block J, Hill R. Organic medicinal and pharmaceutical chemistry. Philadelphia: Lippincott Williams and Wilkins; 2010.
3. Diwedi Rohini, Alexandar A, Chandrasekar MJN. Preparation and in vitro evaluation of sustained release tablet formulations of metformin HCL. Asian J Pharm Clin Res 2012;5:45-8.
4. Harvey RA, Clark MA, Finkel R, Rey JA, Whalen K. Lippincottâ€™s illustrated reviews: pharmacology. Philadelphia: Wolters Kluwer; 2012.
5. Soyman Z, Daniel E Kel e klis. Polycystic ovary syndrome and metformin. J Obstetrics Gynaecol 2011;1:2.
6. Tripathi KD. Essentials of medical pharmacology. [ed.] M. Tripathi. 7th Edition. JP Medical Ltd; 2013. p. 275.
7. Ruhidas B, Naskar D, Banerjee S, Karan S, Chatterjee TK. Evaluation of gum katira as a model sustained release adjuvant in the preparation of etodolac loaded microsphere. Indian J Pharm Educ Res 2016;50:1.
8. Nethaji R, Narayanan A, Palanivelu M, Surendiran NS, Ganesan B. Formulation and evaluation of metformin hydrochloride loaded mucoadhesive microspheres. Int J Pharm Chem Biol Sci 2016;6:2.
9. Goswami S, Naik S. Natural gums and its pharmaceutical application. J Sci Innovative Res 2014;3:112-21.
10. Goldstein AM, Alter EN, Seaman JK. Guar gum. In Industrial Gums 1973;1:303-21.
11. Sharma S, Kaur J, Sharma G, Thakur KK, Chauhan GS, Chauhan K. Preparation and characterization of pH-responsive guar gum microspheres. Int J Biol Macromol 2013;62:636-41.
12. Gorain B, Choudhury H, Tekade RK, Karan S, Jaisankar P, Pal TK. Comparative biodistribution and safety profiling of olmesartan medoxomil oil-in-water oral nanoemulsion. Regul Toxicol Pharmacol 2016;82:20-31.
13. Huanbutta K, Sittikijyothin W. Development and characterization of seed gums from tamarindus indica and cassia fistula as disintegrating agent for fast disintegrating Thai cordial tablet. Asian J Pharm Sci 2017;12:370-7.
14. Zaied SF, Youssef BM, Desouky O, El Dien MS. Decontamination of gum Arabic with Î³-rays or electron beams and effects of these treatments on the material. Appl Radiat Isot 2007;65:26-31.
15. Pal T, Paul S, Sa B. Polymethylmethacrylate coated alginate matrix microcapsules for controlled release of diclofenac sodium. Pharmacol Pharm 2011;2:56-66.
16. Pavanveena C, Kavitha K, Kumar SA. Formulation and evaluation of trimetazidine hydrochloride loaded chitosan microspheres. Int J Appl Pharm 2010;2:11-4.
17. kaliamurthi S, Selvaraj G. Insight on solid lipid nanoparticles: characterization and application in. J Critical Rev 2016;3:11-6.
18. Dang T, Cui Y, Chen YD, Meng XM, Tang BF, Wu J. Preparation and characterization of colon-specific microspheres of diclofenac for colorectal cancer. Trop J Pharm Res 2015;14:1541-7.
19. Venkateswaramurthy N, Sambathkumar R, Vijayabaskaran M Peruma. Clarithromycin mucoadhesive microspheres for anti-helicobacter pylori therapy: formulation and in vitro evaluation. Int J Curr Pharm Res 2010;12:24-7.
20. Roy S, Manjanna KM. Effect of formulation variables on physicochemical characteristics and drug release properties of oral glipizide microspheres. J Adv Sci Res 2011;2:46-54.
21. Mankala SK, Nagamalli NK, Raprla R, Kommula R. Preparation and characterization of mucoadhesive microcapsules of gliclazide with natural gums. Stamford J Pharm Sci 2011;4:38-48.
22. Mandal AS, Biswas N, Karim KM, Guha A, Chatterjee S, Behera M, et al. Drug delivery system based on the chronobiology-a review. J Controlled Release 2010;147:314-25.
23. Ramesh DV. Comparison of oil-in-oil, water-in-oil-in-water and melt encapsulation techniques for the preparation of controlled release B12 poly (Ð„-cprolactone) microparticles. Trends Biomaterials Artificial Organs 2009;23:21-3.
24. R Dinarvand SH, Moghadam A Sheikhi, F Atyabi. Effect of surfactant HLB and different formulation variables on the properties of poly-D,L-lactide micro-spheres of naltrexone prepared by double emulsion technique. J Microencapsulation 2005;22:139-51.
25. MK Yeh, SM Tung, DW Lu, CH Chiang. Formulation factors for preparing an ocular biodegradable delivery system of 5-fluorouracil microparticles. J Microencapsulation 2001;18:507-19.
26. Ganesh Subbiah, Kumar DS, Kumar BS, Abhilash R, Bharadwaj PS, Prudhviraj KVS, et al. Controlled release formulation and evaluation of idarubicin microsphere using biodegradable hydrophilic and hydrophobic polymer mixtures. Asian J Pharm Clin Res 2010;3:179-82.
27. MK Lai, RCC Tsiang. Microencapsulation of acetaminophen into poly(L-lactide) by three different emulsion solvent-evaporation methods. J Microencapsulation 2005;22:261-74.
28. Park G, Crotts TG. Protein delivery from poly (lactic-co-glycolic Acid) biodegradable microspheres: release kinetics and stability issues. J Micro-Encapsulation 1998;15:699-713.
29. DV Ramesh. Comparison of oil-in-oil, water-in-oil-in-water and melt encapsulation techniques for the preparation of controlled release B12 poly (Ð„-cprolactone) microparticles. Trends Biomater Artif Organs 2009;23:21-3.
30. Ong M, Li N, Sun S, Tiedt LR, Liebenberg W, de Villiers MM. Effect of viscosity and concentration of wall former, emulsifier and pore-inducer on the properties of amoxicillin microcapsules prepared by emulsion solvent evaporation. Il Farmaco 2005;60:261-7.