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).
Similar content being viewed by others
References
Law MFL, Deasy PB. Use of hydrophilic polymers with microcrystalline cellulose to improve extrusionspheronization. Eur J Pharm Biopharm. 1998;48:57–65.
Goskonda SR, Upadrashta SM. Avicel RC-591/chitosan beads by extrusion-spheronization technology. Drug Dev Ind Pharm. 1993;19:915–927.
Rubinstein A. Approaches and opportunities in colon-specific drug delivery. Crit Rev Ther Drug Carrier Syst. 1995;12:101–149.
Hovgaard L, Brondsted H. Current applications of polysaccharides in colon targeting. Crit Rev Ther Drug Carrier Syst. 1996;13:185–223.
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.
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.
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.
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.
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.
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.
Wakerly Z, Fell JT, Attwood D, Parkins DA. Pectin/ethylcellulose film coating formulations for colonic drug delivery. Pharm Res. 1996;13:1210–1212.
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.
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.
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.
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.
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.
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.
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.
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.
Kleinebudde P. Use of a power-consumption-controlled extruder in the development of pellet formulations. J Pharm Sci. 1995;84:1259–1264.
Schroder M, Kleinebudde P. Structure of disintegrating pellets with regard to fractal geometry. Pharm Res. 1995;12:1694–1700.
Esbensen K, Schoenkopf S, Midtgaard T, Guyot D. Multivariate Analysis in Practice. Trondheim, Norway: Camo ASA; 1994.
Martens H, Naes T. Multivariate Calibration. Chichester: Wiley and Sons; 1989.
Martens H, Efron B. The Jackknife, the Bootstrap and Other Resampling Plans. Philadelphia, PA: Society for Industrial and Applied Mathematics; 1982.
Dyrstad K. Selective improvements in multiquality products assisted by rotated principal components. Chemometr Intell Lab Syst. 1998;42:115–124.
Rolin C. Calcium sensitivity of high ester citrus pectins, in: Phillips GO, Williams PA, Wedlock DJ, ed. Gums and stabilisers for the food industry. London: Elsivier; 1994;413–421.
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.
Author information
Authors and Affiliations
Corresponding author
Additional information
Published: December 1, 2001
Rights and permissions
About this article
Cite this article
Tho, I., Kleinebudde, P. & Sande, S.A. Extrusion/spheronization of pectin-based formulations. I. Screening of important factors. AAPS PharmSciTech 2, 26 (2001). https://doi.org/10.1208/pt020426
Received:
Accepted:
Published:
DOI: https://doi.org/10.1208/pt020426