Design and Characterization of Dual Drug Loaded Microspheres for Colon Drug Targeting
The present investigation was focus to prepared and characterized eudragit coated pectin microspheres for the delivery of mesalamine and prednisolone to the colon. The pectin microspheres were prepared using emulsion dehydration technique. A 33 full factorial design (three variables in three levels) was employed to evaluate the combined effect of the selected independent variables: drugs to polymer ratio, emulsifier concentrations and stirring speed on dependent variables such as particle size and size distribution, percentage yield, % drug entrapment and swelling ratio. Optimized formulation i.e. F18, F24, and F27 were coated with eudragit S100 by the solvent evaporation technique to prevent drug release in the stomach. Eudragit S100 coated pectin microspheres were further characterized for coating thickness and in-vitro release kinetics. The cumulative percent drug release of mesalamine and prednisolone from formulation in pH 7.4 phosphate buffer was found to be 97.01 + 1.35% and 96.89 + 0.67% for mesalamine and prednisolone, respectively. Optimized formulation (F24) was characterized for in-vivo studies. The eudragit-coated pectin microspheres may improve therapeutic efficacy by local action and reduce the side effects by minimizing the systemic absorption of mesalamine and prednisolone. Amalgamation of mesalamine and prednisolone in therapeutic regimen will show synergism action for treatment of UC.
2. Seth Amidon, Jack E. Brown, Vivek S. Dave. Colon-Targeted Oral Drug Delivery Systems: Design Trends and Approaches. AAPS PharmSciTech 2015; 16:731-741.
3. Kumar P, Mishra B. Colon targeted drug delivery systems--an overview. Curr Drug Deliv 2008; 5:186-98.
4. Burger D, Travis S. Conventional medical management of inflammatory bowel disease. Gastroenterology 2011; 140:1827-1837.
5. Naganuma M, Iwao Y, Ogata H, Inoue N, Funakoshi S, Yamamoto S, Nakamura Y, Ishii H, Hibi T. Measurement of colonic mucosal concentrations of 5-aminosalicylic acid is useful for estimating its therapeutic efficacy in distal ulcerative colitis: comparison of orally administered mesalamine and sulfasalazine. Inflamm Bowel Dis 2001; 7:221-225.
6. Dashora A, Jain, CP. Development and characterization of pectin prednisolone microspheres for colon targeted delivery. International Journal of ChemTech Research 2009; 3:751-757.
7. Laila F, Asghar A, Chandran S. Multiparticulate formulation approach to colon specific drug delivery: current perspectives. J Pharm Pharmaceut Sci 2006; 9:327-338.
8. Maestrelli F, Cirri M, Corti G, Mennini N, Mura P. Development of enteric-coated calcium pectinate microspheres intended for colonic drug delivery. Eur J Pharm Biopharm 2008; 69:508-18.
9. Sinha VR, Kumria R. Polysaccharides in colon-specific drug delivery. Int J Pharm 2001; 224:19–38.
10. Wong TW, Colombo G, Sonvico F. Pectin matrix as oral drug delivery vehicle for colon cancer treatment. AAPS PharmSciTech 2011; 12:201-14.
11. Leopold CS, Eikeler D. Eudragit E as coating material for the pH-controlled drug release in the topical treatment of inflammatory bowel disease (IBD). J Drug Target 1998; 6:85–94.
12. Esposito, E., et al. Pectin-based microspheres: A preformulation study. Annuals New York Academy of Sciences 2001; 994:160-179.
13. Bigucci F, Luppi B, Monacoa L, Cerchiarab T, Zecchi V. Pectin-based microspheres for colon-specific delivery of vancomycin. J Pharm Pharmacol 2009; 61:41-46.
14. Nappinnai M, Sivaneswari S. Formulation optimization and characterization of gastroretentive cefpodoxime proxetil mucoadhesive microspheres using 32 factorial design. J Pharm Research 2013; 7:304-309.
15. Ramazani F, Chen W, Van Nostrum CF, Storm G, Kiessling F, Lammers T, Hennink WE, Kok RJ, Formulation and characterization of microspheres loaded with imatinib for sustained delivery. Int J Pharma 2015; 482:123–130.
16. Kakar S, Batra D, Singh R. Preparation and evaluation of magnetic microspheres of mesalamine (5-aminosalicylic acid) for colon drug delivery. J Acute Disease 2013; 226-231.
17. Lorenzo-Lamosa ML, Remunan-Lopez C, Vila-Jato JL, Alonso MJ. Design of microencapsulated chitosan microspheres for colonic drug delivery. J Control Release 1998; 52:109-118.
18. Obitte N, Chukwu A. The synergistic effect of Landolphia owariensis latex and Eudragit L-100-coated capsules on the in vitro controlled release of metronidazole for possible colon targeting. Asian J Pharm 2011; 5:75–83.
19. Fu-Yin Hsu, Ding-Syuan Yu, Chun-Chiang Huang, Development of pH-sensitive pectinate/alginate microspheres for colon drug delivery J Mater Sci: Mater Med 2013; 24:317–323.
20. Paharia A, Yadav AK, Rai G, Jain SK, Pancholi S S, Agrawal G P, Eudragit-coated pectin microspheres of 5-fluorouracil for colon targeting. AAPS PharmSciTech 2007; 8: E87–E93.
21. Deore KL, Thombre NA, Gide PS. Formulation and development of tinidazole microspheres for colon targeted drug delivery System, J Pharm Res 2013; 6:158-165.
22. Murat M M H, Ulvi D, Neslihan Y, Neﬂe K, Smail T, Serpil F, Cengiz A, Murat A, Melih K, Fatih H. The effects of Gingko biloba extract on acetic acid induced colitis in rats Turk. J Gastroenterol 2006; 17:177-182.
23. Melgar S, Bjurell M, Mice with experimental colitis shows an altered metabolism with decreased metabolic rate. Am J Physiol Gastrointest Liver Physio 2007; 292:G165-G172.
24. Agarwal T, Narayana SNGH, Pal K, Pramanik K, Giri S, Banerjee I. Calcium alginate-carboxymethyl cellulose beads for colon-targeted drug delivery. Int J Biol Macromol 2015; 75:409–417.
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