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. 2007 Aug 10;8(3):E99–E109. doi: 10.1208/pt0803064

Influence of chitosan type on the properties of extruded pellets with low amount of microcrystalline cellulose

Nattawut Charoenthai 1,, Peter Kleinebudde 2, Satit Puttipipatkhachorn 1,
PMCID: PMC2750560  PMID: 18181559

Abstract

The purpose of this research was to study the influence of type of chitosan with different molecular weights, ie, 190 and 419 kDa, on properties of pellets prepared by extrusion/ spheronization. The formulations, consisting of acetaminophen as model drug, chitosan, microcrystalline cellulose (MCC), and dibasic calcium phosphate dihydrate with/without sodium alginate, were extruded using a twin-screw extruder and water as the granulating liquid. With 30% wt/wt MCC and no added sodium alginate, spherical pellets were produced containing low and high molecular weight chitosan at a maximum amount of 60% and 40% wt/wt, respectively. With sodium alginate (2.5% wt/wt), pellets with either type of chitosan (60% wt/wt), MCC (17.5% wt/wt), and acetaminophen (20% wt/wt) could be produced indicating an improved pelletforming ability. Type and amount of chitosan and added sodium alginate affected physical properties of pellets including size, roundness, crushing force, and drug release. Low molecular weight chitosan produced pellets with higher mean diameter, sphericity, and crushing force. Additionally, the pellets made of low molecular weight chitosan and added sodium alginate showed faster drug release in 0.1 N HCl but had slower drug release in pH 7.4 phosphate buffer. This indicated that drug release from pellets could be modified by the molecular weight of chitosan. In conclusion, the molecular weight of chitosan had a major influence on formation, physical properties, and drug release from the obtained pellets.

Keywords: Chitosan, sodium alginate, pellets, extrusion/spheronization, drug release

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References

  • 1.Bechgaard H, Nielsen GH. Controlled release multiple units and single-unit doses. Drug Dev Ind Pharm. 1978;4:53–67. doi: 10.3109/03639047809055639. [DOI] [Google Scholar]
  • 2.Reynolds AD. A new technique for the production of spherical particles. Mfg Chem Aerosol News. 1970;41:40–43. [Google Scholar]
  • 3.Vervaet C, Baert L, Remon JP. Extrusion-spheronisation: a literature review. Int J Pharm. 1995;116:131–146. doi: 10.1016/0378-5173(94)00311-R. [DOI] [Google Scholar]
  • 4.O'Conner RE, Schwartz JB. Spheronization II: drug release from drug-diluent mixture. Drug Dev Ind Pharm. 1985;11:1837–1857. doi: 10.3109/03639048509057702. [DOI] [Google Scholar]
  • 5.Schröder M, Kleinebudde P. Development of disintegrating pellets obtained from extrusion/spheronization. J Pharm Sci. 1995;1:415–418. [Google Scholar]
  • 6.Zimm KR, Schwartz JB, O'Connor RE. Drug release from a multiparticulate pellet system. Pharm Dev Technol. 2007;1:37–42. doi: 10.3109/10837459609031416. [DOI] [PubMed] [Google Scholar]
  • 7.Tapia C, Buckton G, Newton JM. Factors influencing the mechanism of release from sustained release matrix pellets, produced by extrusion/spheronisation. Int J Pharm. 1993;92:211–218. doi: 10.1016/0378-5173(93)90282-K. [DOI] [Google Scholar]
  • 8.Goskonda SR, Upadrashta SM. Avicel RC-591/chitosan beads by extrusion-spheronization technology. Drug Dev Ind Pharm. 1993;19:915–927. doi: 10.3109/03639049309062991. [DOI] [Google Scholar]
  • 9.Santos H, Veiga F, Pina M, Podezeck F, Sousa J. Physical properties of chitosan pellets produced by extrusion-spheronisation: influence of formulation variables. Int J Pharm. 2002;246:153–169. doi: 10.1016/S0378-5173(02)00376-9. [DOI] [PubMed] [Google Scholar]
  • 10.Chatchawalsaisin J, Podczeck F, Newton JM. The influence of chitosan and sodium alginate and formulation variables on the formation and drug release from pellets prepared by extrusion/spheronisation. Int J Pharm. 2004;275:41–60. doi: 10.1016/j.ijpharm.2004.01.025. [DOI] [PubMed] [Google Scholar]
  • 11.Sriamornsak P, Nunthanid J, Luangtana-anan M. Puttipipatkhachorn S. Alginate-based pellets prepared by extrusion/spheronization: a preliminary study on the effect of additive in granulating liquid. Eur J Pharm Biopharm. 2007;67:227–235. doi: 10.1016/j.ejpb.2006.11.007. [DOI] [PubMed] [Google Scholar]
  • 12.Neau SH, Chow MY, Durrani MJ. Fabrication and characterization of extruded and spheronized beads containing Carbopol 974P. Int J Pharm. 2007;131:47–55. doi: 10.1016/0378-5173(95)04293-8. [DOI] [Google Scholar]
  • 13.Bommareddy GS, Paker-Leggs S, Saaripella KK, Neau SH. Extruded and spheronized beads containing Carbopol® 974P to deliver nonelectrolytes and salts of weakly basic drugs. Int J Pharm. 2006;321:62–71. doi: 10.1016/j.ijpharm.2006.05.017. [DOI] [PubMed] [Google Scholar]
  • 14.Steckel H, Mindermann-Nogly F. Production of chitosan pellets by extrusion/spheronization. Eur J Pharm Biopharm. 2004;57:107–114. doi: 10.1016/S0939-6411(03)00156-5. [DOI] [PubMed] [Google Scholar]
  • 15.Agrawal AM, Howard MA, Neau SH. Extruded and spheronized beads containing no microcrystalline cellulose: influence of formulation and process variables. Pharm Dev Technol. 2004;9:197–217. doi: 10.1081/PDT-120030250. [DOI] [PubMed] [Google Scholar]
  • 16.Charoenthai N, Kleinebudde P, Puttipipatkhachorn S. Use of chitosan-alginate as alternative pelletization aid to microcrystalline cellulose in extrusion/spheronization. J Pharm Sci. 2007;96:2469–2484. doi: 10.1002/jps.20855. [DOI] [PubMed] [Google Scholar]
  • 17.Tho I, Sande SA, Kleinebudde P. Disintegrating pellets from a water-insoluble pectin derivative produced by extrusion/spheronisation. Eur J Pharm Biopharm. 2003;56:371–380. doi: 10.1016/S0939-6411(03)00071-7. [DOI] [PubMed] [Google Scholar]
  • 18.Bornhöft M, Thommes M, Kleinebudde P. Preliminary assessment of carrageenan as excipient for extrusion/spheronisation. Eur J Pharm Biopharm. 2005;59:127–131. doi: 10.1016/j.ejpb.2004.05.007. [DOI] [PubMed] [Google Scholar]
  • 19.Thommes M, Kleinebudde P. Use ofk-carrageenan as alternative pelletisation aid to microcrystalline cellulose in extrusion/spheronisation I: influence of type and fraction of filler. Eur J Pharm Biopharm. 2006;63:59–67. doi: 10.1016/j.ejpb.2005.10.002. [DOI] [PubMed] [Google Scholar]
  • 20.Thommes M, Kleinebudde P. Use ofk-carrageenan as alternative pelletisation aid to microcrystalline cellulose in extrusion/spheronisation II: influence of drug and filler type. Eur J Pharm Biopharm. 2006;63:68–75. doi: 10.1016/j.ejpb.2005.10.003. [DOI] [PubMed] [Google Scholar]
  • 21.Felt O, Buri P, Gurny R. Chitosan: a unique polysaccharide for drug delivery. Drug Dev Ind Pharm. 1998;24:979–993. doi: 10.3109/03639049809089942. [DOI] [PubMed] [Google Scholar]
  • 22.Ilium L. Chitosan and its use as a pharmaceutical excipient. Pharm Res. 1998;15:1326–1331. doi: 10.1023/A:1011929016601. [DOI] [PubMed] [Google Scholar]
  • 23.Paul W, Sharma CP. Chitosan, a drug carrier for the 21st century: a review. STP Pharma Sci. 2000;10:5–22. [Google Scholar]
  • 24.Nunthanid J, Puttipipatkhachorn S., Yamamoto K, Peck GE. Physical properties and molecular behavior of chitosan films. Drug Dev Ind Pharm. 2001;27:143–157. doi: 10.1081/DDC-100000481. [DOI] [PubMed] [Google Scholar]
  • 25.Voegele D, Brockmeier D, Von Hattingberg HM, Lippold BC. Mean dissolution time—a parameter for testing release condition comparability. Acta Pharm Technol. 1983;29:167–174. [Google Scholar]
  • 26.Costa FO, Sousa JJS, Pais AACC, Formosinho SJ. Comparison of dissolution profiles of ibuprofen pellets. J Control Release. 2003;89:199–212. doi: 10.1016/S0168-3659(03)00033-6. [DOI] [PubMed] [Google Scholar]
  • 27.Korsmeyer RW, Gurny R, Doelker EM, Buri P, Peppas NA. Mechanism of solute release from porous hydrophilic polymers. Int J Pharm. 1983;15:25–35. doi: 10.1016/0378-5173(83)90064-9. [DOI] [PubMed] [Google Scholar]
  • 28.Ritger PL, Peppas NA. A simple equation for description of solute release II. Fickian and anomalous release from swellable devices. J Control Release. 1987;5:37–42. doi: 10.1016/0168-3659(87)90035-6. [DOI] [PubMed] [Google Scholar]
  • 29.Takahashi T, Takayama K, Machida Y, Nagai T. Characteristics of polyion complexes of chitosan with sodium alginate and sodium polyacrylate. Int J Pharm. 1990;61:35–41. doi: 10.1016/0378-5173(90)90041-2. [DOI] [Google Scholar]
  • 30.Baert L, Fanara D, Debaets P, Remon JP. Instrumentation of a gravity feed extruder and the influence of the composition of binary and ternary mixtures on the extrusion force. J Pharm Pharmacol. 1991;43:745–749. doi: 10.1111/j.2042-7158.1991.tb03475.x. [DOI] [PubMed] [Google Scholar]
  • 31.Fielden KE, Newton JM, Rowe RC. The influence of moisture content on spheronization of extrudate processed by a ram extruder. Int J Pharm. 1993;97:79–92. doi: 10.1016/0378-5173(93)90128-3. [DOI] [Google Scholar]
  • 32.Kleinebudde P, Lindner H. Experiments with an instrumented twin-screw extruder using a single-step granulation extrusion process. Int J Pharm. 1993;94:49–58. doi: 10.1016/0378-5173(93)90008-4. [DOI] [Google Scholar]
  • 33.Lustig-Gustafsson C, Kaur Johal H, Podczeck F, Newton JM. The influence of water content and drug solubility on the formulation of pellets by extrusion and spheronization. Eur J Pharm Sci. 1999;8:147–152. doi: 10.1016/S0928-0987(99)00004-4. [DOI] [PubMed] [Google Scholar]
  • 34.Wan LSC, Heng PWS, Liew CV. Spheronization conditions on spheroid shape and size. Int J Pharm. 1993;96:59–65. doi: 10.1016/0378-5173(93)90212-X. [DOI] [Google Scholar]
  • 35.Blair HS, Guthrie J, Law T, Turkington P. Chitosan and modified chitosan membranes I: preparation and characterization. J Appl Polym Sci. 1987;33:641–645. doi: 10.1002/app.1987.070330226. [DOI] [Google Scholar]
  • 36.Hodsdon AC, Mitchell JR, Davies MC, Melia CD. Structure and behaviour in hydrophilic matrix sustained release dosage forms 3: the influence of pH on the sustained-release performance and internal gel structure of sodium alginate matrices. J Control Release. 1995;33:143–152. doi: 10.1016/0168-3659(94)00076-7. [DOI] [Google Scholar]
  • 37.Fernández-Hervás M, Holgado M, Fini A, Fell JT. In vitro evaluation of alginate beads of diclofenac salt. Int J Pharm. 1998;163:23–34. doi: 10.1016/S0378-5173(97)00333-5. [DOI] [Google Scholar]
  • 38.Murata Y, Miyamoto K, Kawashima S. Additive effect of chondroitin sulfate and chitosan on drug release from chitosan-induced alginate gel beads. J Control Release. 2007;38:101–108. doi: 10.1016/0168-3659(95)00098-4. [DOI] [Google Scholar]

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