AAPS PharmSciTech

, Volume 9, Issue 1, pp 295–301 | Cite as

Preliminary Investigation on the Development of Diltiazem Resin Complex Loaded Carboxymethyl Xanthan Beads

  • Somasree Ray
  • Sabyasachi Maiti
  • Biswanath SaEmail author
Research Article Themed Issue: Oral Controlled Release Development and Technology Guest Editors: Stephen Howard and Jian-Xin Li


The objective of this study was to develop a multiunit sustained release dosage form of diltiazem using a natural polymer from a completely aqueous environment. Diltiazem was complexed with resin and the resinate-loaded carboxymethyl xanthan (RCMX) beads were prepared by interacting sodium carboxymethyl xanthan (SCMX), a derivatized xanthan gum, with Al+3 ions. The beads were evaluated for drug entrapment efficiency (DEE) and release characteristics in enzyme free simulated gastric fluid (SGF, HCl solution, pH 1.2) and simulated intestinal fluid (SIF, USP phosphate buffer solution, pH 6.8). Increase in gelation time from 5 to 20 min and AlCl3 concentration from 1 to 3% decreased the DEE respectively from 95 to 79% and 88.5 to 84.6%. However, increase in gum concentration from 1.5 to 2.5% increased the DEE from 86.5 to 90.7%. The variation in DEE was related to displacement of drug from the resinate by the gel forming Al+3 ions. While 75–82% drug was released in 2 h in SGF from various beads, 75 to 98% drug was released in 5 hour in SIF indicating the dependence of drug release on pH of dissolution media. Although the beads maintained their initial integrity throughout the dissolution process in both media, as evident from scanning electron microscopic studies, the faster release in SGF was accounted for higher swelling of the beads in SGF than in SIF. When release data (up to 60%) was fitted in power law expression, the drug release was found to be controlled by diffusion with simultaneous relaxation phenomena.

Key words

carboxymethyl xanthan beads diltiazem entrapment release resinate 



The authors wish to thank M/s. Sun Pharmaceutical Industries Ltd., and M/s Ion Exchange (India) Pvt. Ltd., for the generous gift of diltiazem and Indion 254 respectively. Authors are also grateful to Dr P Chakraborty, Professor, Metallurgy Department, Jadavpur University for carrying out the Scanning Electron Microscopic studies.


  1. 1.
    M. R. Harris, and I. Ghebre-Sellassie. Aqueous Polymeric Coating for Modified Release Pellets. In J. W. McGinity (ed.), Aqueous Polymeric Coatings for Pharmaceutical Dosage Forms, Marcel Dekker Inc, New York, 1989, p. 64.Google Scholar
  2. 2.
    S. P. Vyas, and R. P. Khar. Controlled Drug Delivery Concepts and Advances, Delhi, Vallabh Prakashan, 2002, p. 102.Google Scholar
  3. 3.
    H. Tomida, C. Mizuo, C. Nakamura, and S. Kiryu. Imipramine release from Ca-alginate gel beads. Chem. Pharm. Bull. 41:1475–1477 (1993).Google Scholar
  4. 4.
    S. Shiraishi, T. Imai, and M. Otagiri. Controlled–release preparation of indomethacin using calcium alginate gel. Biol. Pharm. Bull. 16:1164–1168 (1993).Google Scholar
  5. 5.
    K. Tatesnita, S. Sugawara, T. Imai, and M. Otagiri. Preparation and evaluation of a controlled release formulation of nifedipine using calcium alginate beads. Biol. Pharm. Bull. 16:420–424 (1993).Google Scholar
  6. 6.
    P. R. Hari, T. Chandy, and C. P. Sharma. Chitosan/calcium alginate microcapsules for intestinal delivery of nitrofurantoin. J. Microencap. 13:319–329 (1996).CrossRefGoogle Scholar
  7. 7.
    L. Y. Lim, and S. C. L. Wan. Propranolol hydrochloride binding in calcium alginate beads. Drug Dev. Ind. Pharm. 23:973–980 (1997).CrossRefGoogle Scholar
  8. 8.
    P. Aslani, and R. A. Kennedy. Studies on diffusion in alginate gels. I. Effect of cross-linking with calcium or zinc ions on diffusion of acetaminophen. J. Control. Rel. 42:75–82 (1996).CrossRefGoogle Scholar
  9. 9.
    B. J. Lee, G. H. Min, and J. H. Cui. Correlation of drug solubility with trapping efficiency and release characteristics of alginate beads. Pharm. Pharmacol. Commun. 5:85–89 (1999).Google Scholar
  10. 10.
    L. S. Liu, S. G. Liu, S. Y. Ng, N. Froix, T. Ohno, and J. Heller. Controlled release of interleukin-2 for tumor immunotherapy using alginate/chitosan porous microspheres. J. Control. Rel. 43:65–74 (1997).CrossRefGoogle Scholar
  11. 11.
    T. Yotsuyanagi, T. Ohkubo, T. Ohhashi, and K. Ikeda. Calcium induced gelation of alginic acid and pH-sensitive reswelling of dried gels. Chem. Pharm. Bull. 35:1555–1563 (1987).Google Scholar
  12. 12.
    M. L. González Rodríguez, M. A. Holgado, C. Sánchez-Lafuente, A. M. Rabasco, and A. Fini. Alginate/chitosan particulate systems for sodium diclofenac release. Int. J. Pharm. 232:225–234 (2002).CrossRefGoogle Scholar
  13. 13.
    H. Tomida, C. Mizuo, C. Nakamura, and S. Kiryu. Imipramine release from Ca-alginate gel beads. Chem. Pharm. Bull. 41:1475–1477 (1993).Google Scholar
  14. 14.
    A. Halder, S. Mukherjee, and B. Sa. Development and evaluation of polyethyleneimine-treated calcium alginate beads for sustained release of diltiazem. J. Microencap. 22(1):67–80 (2005).CrossRefGoogle Scholar
  15. 15.
    A. Halder, S. Maiti, and B. Sa. Entrapment efficiency and release characteristics of polyethyleneimine-treated or -untreated calcium alginate beads loaded with propranolol–resin complex. Int. J. Pharm. 302:84–94 (2005).CrossRefGoogle Scholar
  16. 16.
    K. S. Kang, and D. J. Pettitt. Xanthan, Gellan, Welan and Rhamsan. In R. L. Whistler, and J. N. BeMiller (eds.), Industrial Gums, Polysaccharides and Their Derivatives, Academic, New York, 1993, pp. 343–393.Google Scholar
  17. 17.
    B. Katzbauer. Properties and applications of xanthan gum. Polym. Degrad. Stabil. 59:81–84 (1998).CrossRefGoogle Scholar
  18. 18.
    G. Bumphrey. Extremely useful new suspending agent. Pharm. J. 237:665–671 (1986).Google Scholar
  19. 19.
    M. M. Talukdar, and J. Plaizier-Vercammen. Evaluation of xanthan gum as hydrophilic matrix for controlled release dosage form preparations. Drug. Dev. Ind. Pharm. 19:1037–1046 (1993).CrossRefGoogle Scholar
  20. 20.
    M. M. Talukdar, A. Michoel, P. Rombaut, and R. Kinget. Comparative study on xanthan gum and hydroxypropyl methylcellulose as matrices for controlled-release drug delivery I. Compaction and in vitro drug release behaviour. Int. J. Pharm. 129:233–241 (1996a).CrossRefGoogle Scholar
  21. 21.
    Z. Yang, B. Song, Q. Li, H. Fan, and F. Ouyang. Preparation of microspheres with microballoons inside for floating drug delivery systems. J. Appl. Polym. Sci. 94:197–202 (2004).CrossRefGoogle Scholar
  22. 22.
    C. H. Chu, H. Kumagai, and K. Nakamura. Application of polyelectrolyte complex gel composed of xanthan and chitosan to the immobilization of Corynebacterium glutamicum. J. Appl. Polym. Sci. 60:1041–1047 (1996).CrossRefGoogle Scholar
  23. 23.
    S. Dumitriu and E. Chornet. Immobilization of xylanase in chitosan–xanthan hydrogels. Biotechnol. Prog. 13:539–545 (1997).CrossRefGoogle Scholar
  24. 24.
    B. Sa and C. M. Setty. Indian Patent Application No 00578/KOL/2004(23.9.04).Google Scholar
  25. 25.
    E. R. Barnhart. Physicians’ Deck Reference, 45th edn, Medical Economics Co. Inc., Oradell, NJ, 1991, pp. 1293.Google Scholar
  26. 26.
    L. S. Goodman and A. Gilman. The Pharmacological Basis of Therapeutics, 7th edn, Macmillan Publishing Company, New York, 1985.Google Scholar
  27. 27.
    M. Chaffman and R. N. Brogden. Diltiazem, a review of its pharmacological properties and therapeutic efficacy. Drugs 29:387–454 (1985).CrossRefGoogle Scholar
  28. 28.
    D. J. Maxxo, C. l. Obetz, and J. Shuster. Diltiazem hydrochloride. In H. Brittain (eds.), Analytical Profiles of Drug Substances and Excipients, Academic Press, New York, 1994, 23, pp. 53–98.Google Scholar
  29. 29.
    W. J. Irwin, K. A. Belaid, and H. O. Alpar. Drug delivery by ion exchange. Part III. Interaction of ester prodrugs of propranolol with cationic exchange resins. Drug Dev. Ind. Pharm. 13:2047–2066 (1987).CrossRefGoogle Scholar
  30. 30.
    R. W. Korsmeyer, R. Gurny, E. Docler, P. Buri, and N. A. Peppas. Mechanism of solute release from porous hydrophilic polymers. Int. J. Pharm. 15:25–35 (1983).CrossRefGoogle Scholar
  31. 31.
    P. Sriamornsak, and S. Sungthongjeen. Modification of theophylline release with alginate gel formed in hard capsules. AAPS:8(3):article51 (2007).Google Scholar
  32. 32.
    C. M. Setty. Development and Evaluation of Novel Microparticulate Drug Delivery System Using Natural Polymer [Ph.D Thesis] Kolkata: Jadavpur University, 2005.Google Scholar
  33. 33.
    A. H. El-Kamel, O. M. N. Al-gohary, and E. A. Hosny. Alginate-diltiazem hydrochloride beads: optimization of formulation factors, in vitro and in vivo bioavailability. J. Microencap. 20:211–225 (2003).CrossRefGoogle Scholar
  34. 34.
    M. Turkoglu, A. Gursay, L. Eroglu, and I. Okar. Effect of aqueous polymer dispersions on properties of diclofenac alginate beads and in vitro evaluation in rats. STP Pharm. Sci. 7:135–140 (1997).Google Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2007

Authors and Affiliations

  1. 1.Gupta College of Technological SciencesAsansol-1India
  2. 2.Centre for Advanced Research in Pharmaceutical Sciences, Department Of Pharmaceutical TechnologyJadavpur UniversityKolkataIndia
  3. 3.Division of Pharmaceutics, Department of Pharmaceutical TechnologyJadavpur UniversityKolkataIndia

Personalised recommendations