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Colon Delivery of Budesonide: Evaluation of Chitosan–Chondroitin Sulfate Interpolymer Complex

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Abstract

The present study was aimed at formulating tablets comprising of coating susceptible to microbial enzyme degradation for releasing budesonide in the colon. Tablets prepared by using Avicel® pH 102 as diluent and Eudragit® L100-55 as binder were coated to a weight gain of 10% w/w employing aqueous mixtures containing chitosan (CH) and chondroitin sulfate (CS). The interpolymer complex between CH and CS was characterized using Fourier transform infrared (FTIR) and differential scanning calorimetery (DSC) studies. The tablets were evaluated for release of budesonide through in vitro in vivo studies. Formation of bonds between –COO− and –OSO −3 groups of CS and –NH +3 groups of CH was evident in the FTIR spectra of these interpolymer complexed (IPC) films. The DSC thermograms of these films revealed one endothermic transition between 190°C and 205°C, suggesting the formation of new bonds in the IPC. The pH sensitive swelling exhibited by these films was observed to be a function of CH concentration. Tablets coated with aqueous mixtures containing 40:60 or 50:50 ratio of CH/CS totally prevented the release of budesonide in pH 1.2 buffer. The peaks (FTIR) and endothermic transitions (DSC) characteristic of interpolymer complexation were observed to remain unaffected after sequential exposure of the films to pH 1.2 and pH 7.4 buffer IP. This proved the versatility of these IPC films for colon delivery. C max of 1,168.99 and 1,174.2 ng/mL, respectively, at 12 and 8 h post-oral dosing of tablets coated with 40:60 or 50:50 ratio of CH/CS was observed in rats. The aqueous CH/CS (40:60) coating could provide a facile method for delivering budesonide to the colon.

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References

  1. Friend DR. New oral delivery systems for treatment of inflammatory bowel disease. Adv Drug Deliv Rev. 2005;57:247–65.

    Article  CAS  PubMed  Google Scholar 

  2. Robinson M. Medical therapy of inflammatory bowel disease for the 21st century. Eur J Surg. 1998;582:90–8.

    Google Scholar 

  3. Rahimi R, Nikfar S, Rezaie A, Abdollahi M. A meta-analysis of broadspectrum antibiotic therapy in patients with active Crohn's disease. Clin Ther. 2006;28:1983–8.

    Article  CAS  PubMed  Google Scholar 

  4. Klein S, Stein J, Dressman J. Site speific delivery of anti-inflammatory drugs in the gastrointestinal tract: an in vitro release model. J Pharm Pharmacol. 2005;57:709–19.

    Article  CAS  PubMed  Google Scholar 

  5. Spencer CM, McTavish D. Budesonide: a review of its pharmacological properties and therapeutic efficacy in inflammatory bowel disease. Drugs. 1995;50:854–72.

    Article  CAS  PubMed  Google Scholar 

  6. Akhgari A, Sadeghi F, Garekani HA. Combination of time-dependent and pH-dependent polymethacrylates single coating formulation for colonic delivery of indomethacin. Int J Pharm. 2006;320:137–42.

    Article  CAS  PubMed  Google Scholar 

  7. Niwa K, Takaya T, Morimoto T, Takada K. Preparation and evaluation of a time-controlled release capsule made of ethylcellulose for colon delivery of drugs. J Drug Target. 1995;3:83–9.

    Article  CAS  PubMed  Google Scholar 

  8. Sinha VR, Kumria R. Microbially triggered drug delivery to the colon. Eur J Pharm Sci. 2003;18:3–18.

    Article  CAS  PubMed  Google Scholar 

  9. Evans DF, Pye G, Bramley R, Clark AG, Dyson TJ, Hardcastle JD. Measurement of gastrointestinal pH profiles in normal ambulant subjects. Gut. 1988;29:1035–41.

    Article  CAS  PubMed  Google Scholar 

  10. Davis SS, Hardy JG, Stockwell A, Taylor MJ, Whalley DR, Wilson CG. The effect of food on the gastrointestinal transit of pellets and an osmotic device (Osmet). Int J Pharm. 1984;21:331–40.

    Article  Google Scholar 

  11. Wong D, Larrabee S, Clifford K, Tremblay J, Friend DR. USP dissolution apparatus II (reciprocating cylinder) for screening of guar gum-based colonic delivery formulations. J Control Rel. 1997;47:73–179.

    Google Scholar 

  12. Raghavan CV, Muthulingam C, Jenita JAJL, Ravi TK. An in vitro in vivo investigation into the suitability of bacterially triggered delivery system for colon targeting. Chem Pharm Bull. 2002;50:892–5.

    Article  CAS  PubMed  Google Scholar 

  13. Siew LF, Basit AW, Newton JM. The properties of amylase ethylcellulose films cast from organic-based solvents as potential coatings for colonic drug delivery. Eur J Pharm Sci. 2000;11:133–9.

    Article  CAS  PubMed  Google Scholar 

  14. Ahmed IS. Effect of simulated gastrointestinal conditions on drug release from pectin/ethylcellulose as film coating for drug delivery to the colon. Drug Dev Ind Pharm. 2005;31:465–70.

    Article  CAS  PubMed  Google Scholar 

  15. Gliko-Kabir I, Yagen B, Penhasi A, Rubinstein A. Low swelling, crosslinked guar gum and its potential use as colon-specific drug carrier. Pharm Res. 1998;15:1019–25.

    Article  CAS  PubMed  Google Scholar 

  16. Fan J, Wang K, Liu M, He Z. In vitro evaluations of konjac glucomannan and xanthan gum mixture as the sustained release material of matrix tablet. Carbohydr Polym. 2008;73:241–7.

    Article  CAS  Google Scholar 

  17. Muzzarelli C, Vesna Stanic V, Gobbi L, Tosi G, Muzzarelli R. Spray drying of solutions containing chitosan together with polyuronans and characterisation of the microspheres. Carbohydr Polym. 2004;57:73–82.

    Article  CAS  Google Scholar 

  18. Xia W, Liu P, Liu J. Advance in chitosan hydrolysis by non-specific cellulases. Biores Technol. 2008;99:6751–62.

    Article  CAS  Google Scholar 

  19. Indian Pharmacopeia. Indian Pharmacopeia Commission, Ghaziabad; 2007.

  20. Marvola M, Nykänen P, Rautio S, Isonen N, Autere A-M. Enteric polymers as binders and coating materials in multiple-unit site specific drug delivery systems. Eur J Pharm Sci. 1999;7:259–67.

    Article  CAS  PubMed  Google Scholar 

  21. US Pharmacopeia XXX NF XXV. US Pharmacopeial convention, Rockville; 2007.

  22. Zambito Y, Baggiani A, Carelli V, Serafini MF, Colo GD. Matrices for site specific controlled delivery of 5 fluorouracil to descending colon. J Control Release. 2005;102:669–77.

    Article  CAS  PubMed  Google Scholar 

  23. Rodríguez M, Vila-Jato J, Torres D. Design of a new multiparticulate system for potential site-specific and controlled drug delivery to the colonic region. J. Control. Rel. 1998;55:67–77.

    Article  Google Scholar 

  24. Rubinstein A, Radai R, Ezra M, Pathak S, Rokem JS. In vitro evaluation of calcium pectinate: a potential colon specific drug delivery carrier. Pharm Res. 1993;10:258–63.

    Article  CAS  PubMed  Google Scholar 

  25. Gupta M, Bhargava HN. Develpoment and validation of high performance liquid chromatographic method for the analysis of budesonide. J Pharm Biomed Anal. 2006;40:423–8.

    Article  CAS  PubMed  Google Scholar 

  26. Sui W, Huang L, Wang J, Bo Q. Preparation and properties of chitosan chondroitin sulfate complex microcapsules. Colloids and Surfaces B Biointerfaces. 2008;65:69–73.

    Article  CAS  Google Scholar 

  27. Kemp W. Infrared spectroscopy, in organic spectroscopy. London: MacMillan; 1991.

    Google Scholar 

  28. Berger J, Reist M, Mayer JM, Felt O, Peppas NA, Gurny R. Structure and interactions in covalently and ionically crosslinked chitosan hydrogels for biomedical applications. Eur J Pharm Biopharm. 2004;57:19–34.

    Article  CAS  PubMed  Google Scholar 

  29. Hawksworth G, Drasar BS, Hill MJ. Intestinal bacteria and the hydrolysis of glycosidic bonds. J Med Microbiol. 1971;155:451–9.

    Article  Google Scholar 

  30. Zhang H, Alsara IA, Neau SH. An in vitro evaluation of a chitosan containing multiparticulate system for macromolecular delivery to the colon. Int J Pharm. 2002;239:197–205.

    Article  CAS  PubMed  Google Scholar 

  31. Ofori-Kwakye K, Fell JT. Biphasic drug release from film coated tablets. Int J Pharm. 2003;250:431–40.

    Article  CAS  PubMed  Google Scholar 

  32. Möllmann HW, Hochhaus G. Pharmacokinetics and pharmacodynamics of budesonide after oral application of 1 × 3 mg budesonide as Budenofalk 3 mg capsules to healthy subjects with and without breakfast. Data on file, Dr. Falk Pharma, Freiburg/Germany; 1998.

  33. Edsbacker S, Larsson P, Wollmer P. Gut delivery of budesonide, a locally active corticosteroid, from plain and controlled-release capsules. Eur J Gastroenterol Hepatol. 2002;14:1357–62.

    Article  PubMed  Google Scholar 

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Acknowledgments

The author wish to acknowledge the help rendered by M/S Scientific and Digital Systems, New Delhi, India for providing the facilities of Texture Analyzer for carrying out mechanical tests on CH/CS IPC films.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India

    Gurpreet Kaur, Vikas Rana, Subheet Jain & Ashok K. Tiwary

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  1. Gurpreet Kaur
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  2. Vikas Rana
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  3. Subheet Jain
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Correspondence to Ashok K. Tiwary.

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Kaur, G., Rana, V., Jain, S. et al. Colon Delivery of Budesonide: Evaluation of Chitosan–Chondroitin Sulfate Interpolymer Complex. AAPS PharmSciTech 11, 36–45 (2010). https://doi.org/10.1208/s12249-009-9353-8

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