Skip to main content
PMC home page
AAPS PharmSciTech logoLink to AAPS PharmSciTech
. 2015 Feb 19;2(4):54–62. doi: 10.1007/BF02830566

Extrusion/spheronization of pectin-based formulations. I. Screening of important factors

Ingunn Tho 1,✉, Peter Kleinebudde 2, Sverre Arne Sande 1
PMCID: PMC2784841  PMID: 14727863

Abstract

This study investigated the possibility of producing pectin-based pellets by extrusion/spheronization. The study also identified factors influencing the process and the characteristics of the resulting product. Three types of pectin with different degrees of amid and methoxyl substitution were studied in combination with different granulation liquids (water, calcium chloride, citric acid, and ethanol) and/or microcrystalline cellulose. Pellets were prepared in a power-consumption-controlled, twinscrew extruder; then they were spheronized and dried. The products were characterized by image analysis, sieving analysis, and disintegration and dissolution tests. The results were evaluated by multivariate analysis. Different additives, either in the granulation liquid or in the powder mixture, influenced the ability of the extruded mass to form pellets (the processability) with this technique. However, the various pectin types responded to modifications to a different extent. Short, nearly spherical pellets are obtained with granulation liquids, such as ethanol, that reduce the swelling ability of pectin. Pellets produced with ethanol are, however, mechanically weak and tend to ditintegrate. Pectin molecules with a high degree of free carboxylic acid groups seem to be more sensitive to changes in the granulation liquid. Addition of microcrystalline cellulose as an extrusion aid generally resulted in improvements in shape and size. It was demonstrated that the processability of pectin as well as the characteristics of the products can be influenced in different ways during the process (eg, adding substances to the granulation liquid or to the powder mixture).

Keywords: Pectin, Pellets, Extrusion, Spheronization, Multivariate analysis

Full Text

The Full Text of this article is available as a PDF (10.6 MB).

References

  • 1.Law MFL, Deasy PB. Use of hydrophilic polymers with microcrystalline cellulose to improve extrusionspheronization. Eur J Pharm Biopharm. 1998;48:57–65. doi: 10.1016/S0939-6411(97)00123-9. [DOI] [PubMed] [Google Scholar]
  • 2.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]
  • 3.Rubinstein A. Approaches and opportunities in colon-specific drug delivery. Crit Rev Ther Drug Carrier Syst. 1995;12:101–149. doi: 10.1615/CritRevTherDrugCarrierSyst.v12.i2-3.10. [DOI] [PubMed] [Google Scholar]
  • 4.Hovgaard L, Brondsted H. Current applications of polysaccharides in colon targeting. Crit Rev Ther Drug Carrier Syst. 1996;13:185–223. doi: 10.1615/CritRevTherDrugCarrierSyst.v13.i3-4.10. [DOI] [PubMed] [Google Scholar]
  • 5.Naggar VF, El-Khawas M, Ismail FA, Boraie NA. Pectin, a possible matrix for oral sustained-release preparations of water-soluble drugs. STP Phar Sci. 1992;2:227–234. [Google Scholar]
  • 6.Ahrabi SF, Madsen G, Dyrstad K, Sande SA, Graffner C. Development of pectin matrix tablets for colonic delivery of model drug ropivacaine. Eur J Pharm Sci. 2000;10:43–52. doi: 10.1016/S0928-0987(99)00087-1. [DOI] [PubMed] [Google Scholar]
  • 7.Rubinstein A, Radai R. In vitro and in vivo analysis of colon specificity of calcium pectinate formulations. Eur J Pharm Biopharm. 1995;41:291–295. [Google Scholar]
  • 8.Ashford M, Fell J, Attwood D, Sharma H, Woodhead P. Studies on pectin formulations for colonic drug-delivery. J Control Release. 1994;30:225–232. doi: 10.1016/0168-3659(94)90028-0. [DOI] [Google Scholar]
  • 9.Ashford M, Fell J, Attwood D, Sharma H, Woodhead P. An evaluation of pectin as a carrier for drug targeting to the colon. J Control Release. 1993;26:213–220. doi: 10.1016/0168-3659(93)90188-B. [DOI] [Google Scholar]
  • 10.Wakerly Z, Fell JT, Attwood D, Parkins DA. In vitro evaluation of pectin-based colonic drug delivery systems. Int J Pharm. 1996;129:73–77. doi: 10.1016/0378-5173(95)04251-2. [DOI] [Google Scholar]
  • 11.Wakerly Z, Fell JT, Attwood D, Parkins DA. Pectin/ethylcellulose film coating formulations for colonic drug delivery. Pharm Res. 1996;13:1210–1212. doi: 10.1023/A:1016016404404. [DOI] [PubMed] [Google Scholar]
  • 12.Semde R, Amighi K, Devleeschouwer MJ, Moes AJ. Studies of pectin HM/Eudragit® RL/Eudragit® NE film-coating formulations intended for colonic drug delivery. Int J Pharm. 2000;197:181–192. doi: 10.1016/S0378-5173(99)00467-6. [DOI] [PubMed] [Google Scholar]
  • 13.Macleod GS, Collett JH, Fell JT. The potential use of mixed films of pectin, chitosan and HPMC for bimodal drug release. J Control Release. 1999;58:303–310. doi: 10.1016/S0168-3659(98)00168-0. [DOI] [PubMed] [Google Scholar]
  • 14.Sriamornsak P. Investigation of pectin as a carrier for oral delivery of proteins using calcium pectinate gel beads. Int J Pharm. 1998;169:213–220. doi: 10.1016/S0378-5173(98)00129-X. [DOI] [Google Scholar]
  • 15.Munjeri O, Collett JH, Fell JT. Hydrogel beads based on amidated pectins for colon-specific drug delivery: The role of chitosan in modifying drug release. J Control Release. 1997;46:273–278. doi: 10.1016/S0168-3659(96)01607-0. [DOI] [Google Scholar]
  • 16.Munjeri O, Collett JH, Fell JT, Sharma HL, Smith AM. In vivo behaviour of hydrogel beads based on amidated pectins. Drug Delivery. 1998;5:239–241. doi: 10.3109/10717549809065753. [DOI] [PubMed] [Google Scholar]
  • 17.Pillay V, 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. 1999;59:243–256. doi: 10.1016/S0168-3659(98)00197-7. [DOI] [PubMed] [Google Scholar]
  • 18.Sriamornsak P, Prakongpan S, Puttipipatkhachorn S, Kennedy RA. Development of sustained release theophylline pellets coated with calcium pectinate. J Control Release. 1997;47:221–232. doi: 10.1016/S0168-3659(97)01640-4. [DOI] [Google Scholar]
  • 19.Sriamornsak P, Puttipipatkhachorn S, Prakongpan S. Calcium pectinate gel coated pellets as an alternative carrier to calcium pectinate beads. Int J Pharm. 1997;156:189–194. doi: 10.1016/S0378-5173(97)00192-0. [DOI] [Google Scholar]
  • 20.Kleinebudde P. Use of a power-consumption-controlled extruder in the development of pellet formulations. J Pharm Sci. 1995;84:1259–1264. doi: 10.1002/jps.2600841022. [DOI] [PubMed] [Google Scholar]
  • 21.Schroder M, Kleinebudde P. Structure of disintegrating pellets with regard to fractal geometry. Pharm Res. 1995;12:1694–1700. doi: 10.1023/A:1016209620953. [DOI] [PubMed] [Google Scholar]
  • 22.Esbensen K, Schoenkopf S, Midtgaard T, Guyot D. Multivariate Analysis in Practice. Trondheim, Norway: Camo ASA; 1994. [Google Scholar]
  • 23.Martens H, Naes T. Multivariate Calibration. Chichester: Wiley and Sons; 1989. [Google Scholar]
  • 24.Martens H, Efron B. The Jackknife, the Bootstrap and Other Resampling Plans. Philadelphia, PA: Society for Industrial and Applied Mathematics; 1982. [Google Scholar]
  • 25.Dyrstad K. Selective improvements in multiquality products assisted by rotated principal components. Chemometr Intell Lab Syst. 1998;42:115–124. doi: 10.1016/S0169-7439(98)00016-1. [DOI] [Google Scholar]
  • 26.Rolin C. Calcium sensitivity of high ester citrus pectins. In: Phillips GO, Williams PA, Wedlock DJ, editors. Gums and stabilisers for the food industry. London: Elsivier; 1994. pp. 413–421. [Google Scholar]
  • 27.Millili GP, Schwartz JB. The strength of microcrystalline cellulose pellets: The effect of granulating with water ethanol mixtures. Drug Dev Ind Pharm. 1990;16:1411–1426. doi: 10.3109/03639049009115970. [DOI] [Google Scholar]

Articles from AAPS PharmSciTech are provided here courtesy of American Association of Pharmaceutical Scientists

RESOURCES