OPTIMIZATION AND IN VIVO EVALUATION OF MESALAMINE pH DEPENDENT COATED PELLETS FOR PROMISING ILEOCECAL TARGETING

Hemant H Gangurde; Mayur Ashoka Chordiya; S. Tamizharasi; T. Sivakumar

doi:10.14499/indonesianjpharm0iss0pp277-288

OPTIMIZATION AND IN VIVO EVALUATION OF MESALAMINE pH DEPENDENT COATED PELLETS FOR PROMISING ILEOCECAL TARGETING

Hemant H Gangurde, Mayur Ashoka Chordiya, S. Tamizharasi, T. Sivakumar

Abstract

The present research is a challenge to design, optimized and evaluates mesalamine loaded burst release pH dependent coated pellets for possible ileo-cecal targeting to treat effectively Crohn’s disease. The novelty of this formulation is to release drug specifically and instantly in ileo-cecal region where the chances of Crohn’s disease is more frequent, without being released in upper gastrointestinal tract. Preliminary experimental batches are studied for micromeritic properties and in-vitro drug release. Formulation showed desirable lag time of 5h and dissolution profile were further optimized by applying 32 full factorial design to study the effect of extent of coating (% w/w) Eudragit S100 and croscarmellose sodium over drug layered pellets. The regression equation generated for Q300 (lag time of 5h) = +5.72-31.97*A+0.82*B-0.49*A*B+26.36*A2-0.15*B2 and for Q390 (90% of drug release at pH7.2 within 90 minutes after lag time) = +84.63- 40.09*A+4.62*B. The drug release data of optimized formulation were close to that predicted by the model. Various kinetic models were applied to the all optimized batches. In vivo evaluation of optimized formulations was performed to assess macroscopic, microscopic and biochemical parameters in rats and performed. The present study demonstrates that the mesalamine enteric coated pellets successfully targeted at ileo-cecal region.
Key words: Mesalamine, pulsatile, ileo-cecal targeting, celpheres, Croscarmellose sodium, eudragit S100

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References

Akhgari A., Garekani, HA., Sadeghi F., Azimaie M. 2005. Statistical optimization of indomethacin pellets coated with pHdependent methacrylic polymers for possible colonic drug delivery. Int J Pharm. 305:22–30.

Anal AK., Stevens WF., Lopez, C.R. 2006. Ionotropic cross-linked chitosan microspheres for controlled release of ampicillin. Int J Pharm.312: 166-73.

Ashford M. and Fell JT. 1993. Colonic delivery of drugs: Current status on targeted drug delivery to gastrointestinal tract. Short Hills (NJ). Capsugel, Symposia Series, 133-142.

Biradar SM., Aswanthanarayana BJ., Kulkarni VH., Smita DM., Tarak KC. 2011. Protective effects of Ageratum conyzoides on experimental induced inflammatory bowel disease. J. Pharma. Toxico. 6: 664-678.

Buege JA., Aust SD. 1978. Microsomal lipid peroxidation methods. Enzymologia. 52:302–310.

Cai QX., Zhu KJ., Chen D., Gao LP. 2003. Synthesis, characterization and in-vitro release of aminosalicylic acid and 5-acetyl aminosalicylic acid polyanhydrine–P (CBFAS). Eur. J. Pharm. Biopharm., 55:203-208.

Chourasia MK., Jain SK. 2003. Pharmaceutical approaches to colon targeted drug delivery systems. J. Pharm Pharmaceutical Sci. 6:33-66.

Cotran RS., Kumar V., Robbins ST. 2000. Structural and functional pathology. 6th ed., Rio de Janeiro: Guanabara Koogan,721-737.

Déo SC., Andreazza IF., Possamai JC. 2011. Development of mesalazine pellets coated with methacrylic-derived polymer. Braz. J. Pharm. Sci. 47: 103-109.

El Medany A., Mahgoub A., Mustafa A., Arafa M., Morsi M. 2005. The effects of selective cyclooxygenase-2 inhibitors, celecoxib and rofecoxib, on experimental colitis induced by acetic acid in rats. Eur. J. Pharmacol. 507: 291-9.

Fukui E., Miyamura N., Uemura K., and Kobayashi M. 2000, Preparation of enteric-coated timed release press-coated tablets and evaluation of their function by in-vitro and in vivo tests for colon targeting. Int J Pharm. 204: 7-15.

Gang C., Feng A., Mei-Juan Z., Jin S. 2004. Time and pH-dependent colon-specific drug delivery for orally administered diclofenac sodium and 5-amino salicylic acid. World J Gastroenterol. 10:1769–1774.

Gorgulu S., Yagci G. 2006. Hyperbaric oxygen enhances the efficiency of 5-aminosalicylic acid in acetic acid induced colitis in rats. Dig Dis. Sci. 51: 480–487.

Gupta VK., Beckert E., Price JC. 2001. A novel pH- and time based multiunit potential colonic drug delivery system. I. Development. Int J Pharm. 213:93-102.

Hanauer S.B. 2004. Review article: aminosalicylates in inflammatory bowel disease. Aliment Pharmacol Ther. 20: 60–65.

Kadam VD., Gattani SG. 2010. Development of colon targeted multiparticulate pulsatile drug delivery system for treating nocturnal asthma. Drug Delivery. 17: 343–35.

Klotz U. 2000. The role of aminosalicylates at the beginning of the new millennium in the treatment of chronic inflammatory bowel disease. Eur J Clin Pharmacol. 56: 353–62.

Krawisz JE., Sharon P., Stenson, WF. 1984. Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Assessment of inflammation in rat and hamster models. Gastroenterology. 87:1344–50.

Mastiholimath VS., Dandagi, PM., Jain SS., Gadad AP., Kulkarni, A.R. 2007. Time and pH dependent colon specific, pulsatile delivery of theophylline for nocturnal asthma. Int. J. Pharmaceut. 328:49–56.

Owens CWJ., Belcher RV. 1965. A colorimetric micromethod for determination of glutathione. Biochem. J. 94: 705–711.

Podolsky DK. 2002. Inflammatory bowel disease. N Engl J Med. 347: 417–29.

Qureshi AI., Cohen RD. 2005. Mesalamine delivery systems: do they really make much difference? Adv. Drug Delivery Rev., 57: 281-302.

Rao KP., Patil CC. 2007. Formulation and evaluation of colon targeted oral tablets of naproxen. Ind. J. Pharm. Educ. Res. 146–9.

Shivkumar HN, Desai, B.G., Suresh, S. 2006. Design and evaluation of pH Sensitive multiparticulate system for chronotherapeutic delivery of Diltiazem HCl. Ind. J. Pharm. Sci. 68:781-787.

Watts P., Illum L. 1997. Colonic drug delivery. Drug Dev. Ind. Pharm., 23:893-913.

Weathrall DJ., Ledingham JGG, Warrell DA., 1996. 3rd ed., Gastroenterology, Oxford textbook of medicine. Oxford Medical Publisher, NewYork. 1936-1943.

Williams KL., Fuller, CR., Dieleman LA., DaCosta CM., Haldeman KM., Sartor RB. 2001. Enhanced survivaland mucosal repair after dextran sodium sulfate- induced colitis in transgenic mice that over express growth hormone. Gastroenterology. 120: 925-37.

DOI: http://dx.doi.org/10.14499/indonesianjpharm0iss0pp277-288