Abstract
The purpose of the study was to develop a multiunit sustained release dosage form of diltiazem hydrochloride using a natural polymer, sodium carboxymethyl xanthan gum and polyethyleneimine (PEI) from a completely aqueous environment. PEI treated diltiazem resin complex loaded beads were characterized by morphology, drug entrapment efficiency, in vitro and in vivo release behaviour. 40% and 80% drug was released in 2 hour in pH 1.2 and in 5 to 6 h in pH 6.8 respectively depending on the formulation variables. The prolonged release was attributed to decreased swelling of the beads due to PEI treatment. Maintaining the shape throughout the dissolution process, PEI treated diltiazem resin complex beads released the drug following non-Fickian transport phenomena. In vivo pharmacokinetic evaluation in rabbits shows slow and prolonged drug release when compared with diltiazem solution. The designed beads are suitable for prolonged release of a water soluble drug under a complete aqueous environment using natural gum.
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Al-Saidan, S. M., Krishnaiah, Y. S. R., Patro, S. S., and Satyanaryana, V., In vitro and in vivo evaluation of guar gum matrix tablet for oral controlled release of water soluble diltiazem hydrochloride. AAPS Pharm. Sci. Tech., 6, article 5: E14–21 (2005)
Barnhart, E. R., Physicians’ Deck Reference, 45th edn (Oradell, NJ: Medical Economics Co. Inc.), pp. 1293, (1991).
Bhalerao, S. S., Lalla, J. K., and Rane, M. S., Study of processing parameters influencing the properties of Diltiazem Hydrochloride microspheres. J. Microencap., 18, 299–307 (2001).
Bharadwaj, T. R., Kanwar, M., Lal, R., and Gupta, A., Natural gums and modified natural gums as sustained release carriers. Drug Dev. Ind. Pharm., 26, 1025–1038 (2000).
Bodmeier, R. and Wang, J., Microencapsulation of drugs with aqueous colloidal polymer dispersions. J. Pharm. Sci., 82, 191–194 (1993).
Bumphrey, G., Extremely useful new suspending agent. Pharm. J., 237, 665–671 (1986).
Chaffman, M. and Brogden, R. N., Diltiazem, a review of its pharmacological properties and therapeutic efficacy. Drugs, 29, 387–454 (1985).
Chu, C. H., Kumagai, H., and Nakamura, K., Application of polyelectrolyte complex gel composed of xanthan and chitosan to the immobilization of corynebacterium glutamicum. J. Appl. Polym. Sci., 60, 1041–1047 (1986).
Dumitriu, S. and Chornet, E., Immobilization of xylanase in chitosan-xanthan hydrogels. Biotechnol. Prog., 13, 539–545 (1997).
El-Kamel, A. H., Al-gohary, O. M. N., and Hosny, E. A., Alginate-diltiazem hydrochloride beads: Optimization of formulation factors, in vitro and in vivo bioavailability. J. Microencaps., 20, 211–225 (2003).
Fundueanu, G., Nastruzzi, C., Caprov, A., Desbrieres, J., and Rinaudo, M., Physico chemical characterization of calcium alginate microparticles produced with different methods. Biomaterials, 20, 1427–1435 (1999).
Goodman, L. S. and Gilman, A., The pharmacological basis of therapeutics. 7th edn, Macmillan Publishing Company, New York (1985).
Gugerli, R., Cantana, E., Heinzen, C., Stockar, U. V., and Marison, I. W., Quantitative study of the production and properties of alginate/poly-L-lysine microcapsules. J. Microencaps., 19, 571–590 (2002).
Halder, A., Maiti, S., and Sa, B., Entrapment efficiency and release characteristics of polyethyleneimine-treated or -untreated calcium alginate beads loaded with propranololresin complex. Int. J. Pharm., 302, 84–94 (2005).
Harris, M. R. and Ghebre-Sellassie, I. Aqueous Polymeric Coating for Modified Release Pellets. In: McGinity, J. W., eds. Aqueous Polymeric Coatings for Pharmaceutical Dosage Forms, Marcel Dekker, New York, Inc, pp. 64, (1989).
Kang, K. S., Pettitt, D. J., and Xanthan, G., Welan and Rhamsan In: Whistler, R. L., BeMiller, J. N., eds. Industrial Gums, Polysaccharides and Their Derivatives. Academic Press, New York, pp. 343–393, (1993).
Katzbauer, B., Properties and applications of xanthan gum. Polym. Degrad. Stabil., 59, 81–849 (1998).
Kim, D. and Park, K., Swelling and mechanical properties of superporous hydrogels of poly(acrylamide-co-acrylic acid)/polyethyleneimine interpenetrating polymer networks. Polymer, 45, 189–196 (2004).
Kottke, M. K. and Rhodes, C. T., Limitations of presently available in vitro release data for the prediction of in vivo performance. Drug. Dev. Ind. Pharm, 17, 1157–1176 (1991).
Lim, F. and Sun, A. M., Microencapsulation of islets as bioartificial endocrine pancreas. Science, 210, 908–910 (1980).
Maxxo, D. J., Obetz, C. I., and Shuster, J., Diltiazem hydrochloride. In analytical profiles of drug substances and excipients, edited by H. Brittain, Academic Press. Inc., New York, 23, 53–98 (1994).
O’shea, G. M., Goosen, M. F. A., and Sun, A. M., Prolonged survival of transplanted islets of langerhans encapsulation in a biocompatible membrane. Biochemica. Et. Biophysica. Acta., 804, 133–136 (1984).
Pillay, V. and Fassihi, R., In vitro release modulation from cross linked pellets for site specific drug delivery to the gastrointestinal tract. II. Physicochemical characterization of calcium-alginate, calcium-pectinate and calcium-alginate-pectinate pellets. J. Control. Release, 59, 243–256 (1999).
Ray, S., Maiti, S., and Sa, B., Preliminary investigation on the development of diltiazem resin complex loaded carboxymethyl xanthan beads. AAPS Pharm. Sci. Tech., 9, 295–300 (2008).
Ritger, P. L. and Peppas, N. A., A simple equation for description of solute release. II. Fickian and anomalous release from swellable devices. J. Control. Release, 5, 37–42 (1987).
Rowland, M. and Tozer, T. N., Clinical Pharmacokinetics: Concepts and Applications. New Delhi, India: BI Waverly Pvt Ltd., pp. 478–480, (1996).
Sa, B. and Setty, C. M., Indian Patent Application No 00578/KOL/2004(23.9.04) (2004).
Sriamornsak, P., Preliminary investigation of some polysaccharides as a carrier for cell entrapment. Eur. J. Pharm. Biopharm., 46, 233–236 (1998).
Sriamornsak, P., Effect of calcium concentration, hardening agent and drying condition on release characteristics of oral proteins from calcium pectinate gel beads. Eur. J. Pharm. Sci., 8, 221–227 (1999).
Talukdar, M. M. and Plaizier-Vercammen, J., Evaluation of xanthan gum as hydrophilic matrix for controlled release dosage form preparations. Drug. Dev. Ind. Pharm., 19, 1037–1046 (1993).
Talukdar, M. M., Michoel, A., Rombaut, P., and Kinget, R., 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).
Thimma, R. T. and Tammishetti, S., Barium chloride crosslinked carboxy methyl guar gum beads for gastrointestinal drug delivery. J. Appl. Polym. Sci., 82, 3084–3090 (2001).
Tiyaboonchai, W., Woiszwillo, J., Sims, R. C., and Middaugh, C. R., Insulin containing polyethyleneimine-dextran sulfate nanoparticles. Int. J. Pharm., 255, 139–151 (2003).
Yang, Z., Song, B., Li, Q., Fan, H., and Ouyang, F., Preparation of microspheres with microballoons inside for floating drug delivery systems. J. Appl. Polym. Sci., 94, 197–202 (2004).
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Ray, S., Maiti, S. & Sa, B. Polyethyleneimine-treated xanthan beads for prolonged release of diltiazem: in vitro and in vivo evaluation. Arch. Pharm. Res. 33, 575–583 (2010). https://doi.org/10.1007/s12272-010-0412-1
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DOI: https://doi.org/10.1007/s12272-010-0412-1