NEW DOSAGE FORMS FOR THE DELAYED RELEASE OF MESALAZINE TO THE COLON
Abstract
Objective: The aim of the present work was to develop new solid pharmaceutical delivery systems of mesalazine (5-aminosalicylic acid, 5-ASA) for its colon targeted release.
Methods: Four different types of tablets of the same consistency (matrix and three-layered, with 5-ASA and dextran or pectin as excipients) were placed in a hard gelatin capsule. The 5-ASA release behavior from these formulations was compared to the release of the commercially available Asalazin® in three pH aqueous media in the presence of enzymes.
Results: The produced tablet formulations conformed to the Pharmacopoeia standards. The results showed delayed-release (<10%) during the first two hours, in acidic media (pH 1.5), and modified-release thereafter (pH 6 and 7.4). When dextran was used, the drug release showed more extended-release characteristics, in comparison to pectin formulations, due to the formation of a thicker hydrogel.
Conclusion: The new dosage forms could serve as a per os administration alternative dosage form for the delayed release of mesalazine to the colon
Keywords:
Mesalazine, Delayed release, Pectin, Dextran, Tablets-in-capsule, Pectinex® Ultra SPL
References
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20. Efentakis M, Koutlis A, Vlachou M. Development and evaluation of oral multiple unit and single unit hydrophilic controlled release systems. AAPS PharmSciTech 2000;1:62-70.
21. Lopes CM, Lobo JMS, Pinto JF, Costa P. Compressed mini-tablets as a biphasic delivery system. Int J Pharm 2006;323:93–100.
22. Efentakis M, Peponaki C. Formulation study and evaluation of matrix and three-layer tablet sustained drug delivery systems based on Carbopols with isosorbite nitrate. AAPS PharmSciTech 2008;9:917-23.
23. Vaithiyalingam SR, Sayeed VA. Critical factors in manufacturing multilayered tablets–assessing material attributes, in-process controls, manufacturing process and product performance. Int J Pharm 2010;398:9–13.
24. Gupta P, Vermani K, Garg S. Hydrogels: from controlled release to pH-responsive drug delivery. Drug Discovery Today 2002;7:569–79.
25. Wakerly Z, Fell JT, Attwood D, Parkins D. In vitro evaluation of pectin-based colonic drug delivery systems. Int J Pharm 1996;129:73-7.
26. Fernandez Hervas MJ, Fell JT. Pectin/chitosan mixtures as coatings for colon-specific drug delivery: an in vitro evaluation. Int J Pharm 1998;169:115–9.
27. Macleod GS, Fell JT, Collett JH, Sharma HL, Smith AM. Selective drug delivery to the colon using pectin: chitosan: hydroxypropyl methylcelluslose film-coated tablets. Int J Pharm 1999;187:251-7.
28. Macleod GS, Fell JT, Collett JH. An in vitro investigation into the potential for bimodal drug release from pectin/chitosan/ HPMC-coated tablets. Int J Pharm 1999;188:11-8.
29. Vlachou M, Siamidi A, Efentakis M. Investigation of a novel “Tablets in Capsule” theophylline formulation system for modified release. Pharm Pharmacol In J 2017;5:51-6.
30. Rinaki E, Dokoumetzidis A, Macheras P. The mean dissolution time depends on the dose/solubility ratio. Pharm Res 2003;20:406-8.
31. Khan KA. The concept of dissolution efficiency. Communications J Pharm Pharac 1975;27:48-9.
32. Shah VP, Tsong Y, Sathe P, Liu JP. In vitro dissolution profile comparison–statistics and analysis of the similarity factor, f2. Pharm Res 1998;15:889–96.
33. Costa P, Sousa Lobo JM. Modeling and comparison of dissolution profiles. Eur Pharm Sci 2001;13:123–33.
34. Pharmacopeoa US USP 29-NF24 Rockville MD: USP; 2005.
35. Vlachou M, Siamidi A, Dotsikas Y. Desirability based optimization of new mesalazine modified release formulations: mini tablets in capsules and compression coated tablets. Lett Drug Des Discovery 2019;16:1-10.
36. Siamidi A, Konstantinidou S. Investigation of a novel ‘tablet in capsule’ formulation system for the modified release of mesalazine in gastrointestinal–like fluids. Am Pharm Rev 2018;21:1-3.
37. French DL, Mauger JW. Evaluation of the physicochemical properties and dissolution characteristics of mesalamine: relevance to controlled intestinal drug delivery. Pharm Res 1993;10:1285.
38. Chourasia MK, Jain SK. Polysaccharides for colon targeted drug delivery. Drug Delivery 2004;11:129-48.
39. Sharpe LA, Daily AM, Horava SD, Peppas NA. Therapeutic applications of hydrogels in oral drug delivery. Expert Opin Drug Delivery 2014;11:901–15.
40. Basan H, Gumusderelioglu M, Orbey MT. Release characteristics of salmon calcitonin from dextran hydrogels for colon-specific delivery. Eur J Pharm Biopharm 2007;65:39–46.
41. Hovgaard L, Brøndsted H. Dextran hydrogels for colon-specific drug delivery. J Controlled Release 1995;36:159–66.
42. Ye B, van Langenberg DR. Mesalazine preparations for the treatment of ulcerative colitis. World J Gastrointest Pharmacol Ther 2015;6:137–44.
43. Nugent SG, Kumar D, Rampton DS, Evans DF. Intestinal luminal pH in inflammatory bowel disease: possible determinants and implications for therapy with aminosalicylates and other drugs. Gut 2001;48:571-7.
44. Wei X, Lu Y, Qi J, Wu B, Chen J, Xu H, et al. An in situ crosslinked compression coat comprised of pectin and calcium chloride for colon-specific delivery of indomethacin. Drug Delivery 2015;22:298-305.
2. Ali Baig MM, Fatima S, Fatima M, Siddiqui S, Ali SA, Ilyas MN. Prescription pattern and cost of illness (COI) of inflammatory bowel disease (IBD) in a tertiary care hospital. Int J Pharm Pharm Sci 201;9:44-7.
3. Sharma N, Sharma A, Bhatnagar A, Nishad D, Karwasra R, Khanna K, et al. Novel gum acacia based macroparticles for colon delivery of mesalazine: development and gammascintigraphy study. J Drug Delivery Sci Technol 2019;54:101224.
4. Campregher C, Gasche C. Aminosalicylates. Best Pract Res Clin Gastroenterol 2011;25:535-46.
5. Cesar ALA, Abrantes FA, Farah L, Castilho RO, Cardoso V, Fernandes SO, et al. New mesalamine polymeric conjugate for controlled release: preparation, characterization and biodistribution study. Eur J Pharm Sci 2018;111:57–64.
6. Hartzell AL, Maldonado Gomez MX, Yang J, Hutkins RW, Rose DJ. In vitro digestion and fermentation of 5-formyl-aminosalicylate-inulin: a potential prodrug of 5-aminosalicylic acid. Bioact Carbohydrates Diet Fibre 2013;2:8–14.
7. Nam J, Kim W, Lee S, Jeong S, Yoo JW, Kim MS, et al. Dextran-5-(4-ethoxycarbonylphenylazo) salicylic acid ester, a polymeric colon-specific prodrug releasing 5-aminosalicylic acid and benzocaine, ameliorates TNBS-induced rat colitis. J Drug Target 2016;24:468–74.
8. Zou M, Cheng G, Okamoto H, Hao XHH, An F, De Cui FD, Danjo K. Colon specific drug delivery systems based on cyclodextrin prodrugs: in vivo evaluation of 5-aminosalicylic acid from its cyclodextrin conjugates. World J Gastroenterol 2005;11:7457–60.
9. Yokoe JI, Iwasaki N, Haruta S, Kadono K, Ogawara KI, Higaki K, et al. Analysis and prediction of absorption behavior of colon-targeted prodrug in rats by GI-transitabsorption model. J Controlled Release 2003;86:305–13.
10. Canevari M, Castagliuolo I, Brun P, Cardin M, Schiavon M, Pasut G, et al. Poly (ethylene glycol)-mesalazine conjugate for colon specific delivery. Int J Pharm 2009;368:171–7.
11. Bautzova T, Rabiskova M, Beduneau A, Pellequer Y, Lamprecht A. Bioadhesive pellets increase local 5-aminosalicylic acid concentration in experimental colitis. Eur J Pharm Biopharm 2012;81:379–85.
12. Patole VC, Pandit AP. Mesalamine-loaded alginate microspheres filled in enteric-coated HPMC capsules for local treatment of ulcerative colitis: in vitro and in vivo characterization. J Pharm Investig 2018;48:257–67.
13. Jain V, Prasad D, Jain D, Mishra SK, Singh R. Factorial design-based development of measlamine microspheres for colonic delivery. Biomatter 2011;1:182–8.
14. Jin L, Ding Y, Zhang Y, Xu X, Cao Q. A novel pH–enzyme-dependent mesalamine colon-specific delivery system. Drug Des Dev Ther 2016;10:2021–8.
15. Mohanty S, Panigrahi AK. Multiparticulate drug delivery system for colon targeting. Int J Pharm Pharm Sci 2015;7:433–6.
16. Sardo HS, Saremnejad F, Bagheri S, Akhgari A, Garekani HA, Sadeghi F. A review on 5-aminosalicylic acid colon-targeted oral drug delivery systems. Int J Pharm 2019;558:367-79.
17. Rajesh K, Deveswaran R, Bharath S, Basavaraj BV. Development of mesalazine microspheres for colon targeting. Int J Appl Pharm 2017;9:1-9.
18. Bahekar J, Wadher S. Formulation development of colon targeted mesalamine pellets: in vitro-in vivo release study. Int J Appl Pharm 2019;11:125-32.
19. Sirisha VN, Eswariah MC, Rao AS. A novel approach of locust bean gum microspheres for colonic delivery of mesalamine. Int J Appl Pharm 2018;10:86-93.
20. Efentakis M, Koutlis A, Vlachou M. Development and evaluation of oral multiple unit and single unit hydrophilic controlled release systems. AAPS PharmSciTech 2000;1:62-70.
21. Lopes CM, Lobo JMS, Pinto JF, Costa P. Compressed mini-tablets as a biphasic delivery system. Int J Pharm 2006;323:93–100.
22. Efentakis M, Peponaki C. Formulation study and evaluation of matrix and three-layer tablet sustained drug delivery systems based on Carbopols with isosorbite nitrate. AAPS PharmSciTech 2008;9:917-23.
23. Vaithiyalingam SR, Sayeed VA. Critical factors in manufacturing multilayered tablets–assessing material attributes, in-process controls, manufacturing process and product performance. Int J Pharm 2010;398:9–13.
24. Gupta P, Vermani K, Garg S. Hydrogels: from controlled release to pH-responsive drug delivery. Drug Discovery Today 2002;7:569–79.
25. Wakerly Z, Fell JT, Attwood D, Parkins D. In vitro evaluation of pectin-based colonic drug delivery systems. Int J Pharm 1996;129:73-7.
26. Fernandez Hervas MJ, Fell JT. Pectin/chitosan mixtures as coatings for colon-specific drug delivery: an in vitro evaluation. Int J Pharm 1998;169:115–9.
27. Macleod GS, Fell JT, Collett JH, Sharma HL, Smith AM. Selective drug delivery to the colon using pectin: chitosan: hydroxypropyl methylcelluslose film-coated tablets. Int J Pharm 1999;187:251-7.
28. Macleod GS, Fell JT, Collett JH. An in vitro investigation into the potential for bimodal drug release from pectin/chitosan/ HPMC-coated tablets. Int J Pharm 1999;188:11-8.
29. Vlachou M, Siamidi A, Efentakis M. Investigation of a novel “Tablets in Capsule” theophylline formulation system for modified release. Pharm Pharmacol In J 2017;5:51-6.
30. Rinaki E, Dokoumetzidis A, Macheras P. The mean dissolution time depends on the dose/solubility ratio. Pharm Res 2003;20:406-8.
31. Khan KA. The concept of dissolution efficiency. Communications J Pharm Pharac 1975;27:48-9.
32. Shah VP, Tsong Y, Sathe P, Liu JP. In vitro dissolution profile comparison–statistics and analysis of the similarity factor, f2. Pharm Res 1998;15:889–96.
33. Costa P, Sousa Lobo JM. Modeling and comparison of dissolution profiles. Eur Pharm Sci 2001;13:123–33.
34. Pharmacopeoa US USP 29-NF24 Rockville MD: USP; 2005.
35. Vlachou M, Siamidi A, Dotsikas Y. Desirability based optimization of new mesalazine modified release formulations: mini tablets in capsules and compression coated tablets. Lett Drug Des Discovery 2019;16:1-10.
36. Siamidi A, Konstantinidou S. Investigation of a novel ‘tablet in capsule’ formulation system for the modified release of mesalazine in gastrointestinal–like fluids. Am Pharm Rev 2018;21:1-3.
37. French DL, Mauger JW. Evaluation of the physicochemical properties and dissolution characteristics of mesalamine: relevance to controlled intestinal drug delivery. Pharm Res 1993;10:1285.
38. Chourasia MK, Jain SK. Polysaccharides for colon targeted drug delivery. Drug Delivery 2004;11:129-48.
39. Sharpe LA, Daily AM, Horava SD, Peppas NA. Therapeutic applications of hydrogels in oral drug delivery. Expert Opin Drug Delivery 2014;11:901–15.
40. Basan H, Gumusderelioglu M, Orbey MT. Release characteristics of salmon calcitonin from dextran hydrogels for colon-specific delivery. Eur J Pharm Biopharm 2007;65:39–46.
41. Hovgaard L, Brøndsted H. Dextran hydrogels for colon-specific drug delivery. J Controlled Release 1995;36:159–66.
42. Ye B, van Langenberg DR. Mesalazine preparations for the treatment of ulcerative colitis. World J Gastrointest Pharmacol Ther 2015;6:137–44.
43. Nugent SG, Kumar D, Rampton DS, Evans DF. Intestinal luminal pH in inflammatory bowel disease: possible determinants and implications for therapy with aminosalicylates and other drugs. Gut 2001;48:571-7.
44. Wei X, Lu Y, Qi J, Wu B, Chen J, Xu H, et al. An in situ crosslinked compression coat comprised of pectin and calcium chloride for colon-specific delivery of indomethacin. Drug Delivery 2015;22:298-305.
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SIAMIDI, A., VLACHOU, M., & EFENTAKIS, M. (2020). NEW DOSAGE FORMS FOR THE DELAYED RELEASE OF MESALAZINE TO THE COLON. International Journal of Applied Pharmaceutics, 12(4), 192-196. https://doi.org/10.22159/ijap.2020v12i4.37816
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