Pectin-based systems for colon-specific drug delivery via oral route.

Pectin-derived matrices are now being examined and tested for controlled drug delivery. Pectin is intact in the upper gastrointestinal tract and degraded by colonic microflora. The composition of this microflora remains relatively consistent across a diverse human population. Thus, pectin-derived drug carriers provide promising potential for colon-specific drug delivery. This paper reviews recent developments in pectin-derived formulations. Subjects reviewed include gelation of pectin, calcium cross-linked pectinate, composites of pectin and other polymers, technologies to fabricate pectin into useful drug delivery vehicles, and methods to evaluate release kinetics of incorporated drugs. This article discusses advantages, limitations, and possible future developments in pectin-based formulations with particular emphasis on the field of colon-specific drug delivery.

[1]  L. Vervoort,et al.  In vitro degradation by colonic bacteria of inulinHP incorporated in Eudragit RS films , 1996 .

[2]  T. Vandamme,et al.  The use of polysaccharides to target drugs to the colon , 2002 .

[3]  D. Parkins,et al.  Pectin/Ethylcellulose Film Coating Formulations for Colonic Drug Delivery , 1996, Pharmaceutical Research.

[4]  R. Kohn Ion binding on polyuronates - alginate and pectin , 1975 .

[5]  K. Ofori-Kwakye,et al.  Biphasic drug release: the permeability of films containing pectin, chitosan and HPMC. , 2001, International journal of pharmaceutics.

[6]  M. Turkoğlu,et al.  In vitro evaluation of pectin-HPMC compression coated 5-aminosalicylic acid tablets for colonic delivery. , 2002, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[7]  D. Parkins,et al.  Studies on Amidated Pectins as Potential Carriers in Colonic Drug Delivery , 1997, The Journal of pharmacy and pharmacology.

[8]  R. Bodmeier,et al.  Mechanical Properties of Dry and Wet Cellulosic and Acrylic Films Prepared from Aqueous Colloidal Polymer Dispersions Used in the Coating of Solid Dosage Forms , 1994, Pharmaceutical Research.

[9]  J. Nunthanid,et al.  Calcium pectinate gel beads for controlled release drug delivery : I. Preparation and in vitro release studies , 1998 .

[10]  Correlation of the perceived texture of random coil polysaccharide solutions with objective parameters , 1984 .

[11]  A. Rolland Pharmaceutical particulate carriers : Therapeutic applications , 1993 .

[12]  V. Lee Oral Route of Peptide and Protein Drug Delivery , 1995 .

[13]  J. Mcginity,et al.  Properties of Free Films Prepared from Aqueous Polymers by a Spraying Technique , 1994, Pharmaceutical Research.

[14]  L. Chan,et al.  Drug release properties of pectinate microspheres prepared by emulsification method. , 2002, International journal of pharmaceutics.

[15]  Dominique Duchêne,et al.  Bioadhesion of solid oral dosage forms, why and how? , 1997 .

[16]  A. Sakr,et al.  Studies of the mechanical properties of free films prepared using an ethylcellulose pseudolatex coating system , 1994 .

[17]  B. D. Rohera,et al.  Tensile Properties of Free Films Cast from Aqueous Ethylcellulose Dispersions , 1993, Pharmaceutical Research.

[18]  Delie,et al.  Evaluation of nano- and microparticle uptake by the gastrointestinal tract. , 1998, Advanced drug delivery reviews.

[19]  R R Scheline,et al.  Metabolism of foreign compounds by gastrointestinal microorganisms. , 1973, Pharmacological reviews.

[20]  Thierry Lavé,et al.  Prediction of intestinal absorption: comparative assessment of GASTROPLUS and IDEA. , 2002, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[21]  G. Macleod,et al.  Studies on the physical properties of mixed pectin/ethylcellulose films intended for colonic drug delivery , 1997 .

[22]  E. Morris,et al.  Conformations and interactions of pectins. I. Polymorphism between gel and solid states of calcium polygalacturonate. , 1982, Journal of molecular biology.

[23]  C. O’Driscoll Lipid-based formulations for intestinal lymphatic delivery. , 2002, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[24]  P Langguth,et al.  Intestinal drug efflux: formulation and food effects. , 2001, Advanced drug delivery reviews.

[25]  A. Sandberg,et al.  The effect of citrus pectin on the absorption of nutrients in the small intestine. , 1983, Human nutrition. Clinical nutrition.

[26]  D. Colin INDUSTRIAL PECTIN: SOURCES, PRODUCTION AND APPLICATION , 1990 .

[27]  M. Yalpani Polysaccharides : syntheses, modifications and structure/property relations , 1988 .

[28]  C. Washington,et al.  An investigation into the efficacy of the pectin based anti-reflux formulation-Aflurax. , 2000, International journal of pharmaceutics.

[29]  D. Attwood,et al.  An evaluation of pectin as a carrier for drug targeting to the colon , 1993 .

[30]  A. Rubinstein Microbially controlled drug delivery to the colon , 1990, Biopharmaceutics & drug disposition.

[31]  S. Paoletti,et al.  Ionic Effects on the Conformation, Equilibrium, Properties, and Rheology of Pectate in Aqueous Solutions and Gels , 1986 .

[32]  B. Lippold,et al.  Properties of Aqueous, Plastic Izer-Containing Ethyl Cellulose Dispersions and Prepared Films in Respect to the Production of oral Extended Release Formulations , 1990 .

[33]  D. Attwood,et al.  Studies on pectin formulations for colonic drug delivery , 1994 .

[34]  O. Smidsrod,et al.  Synergistic gelation of alginates and pectins , 1986 .

[35]  C. May,et al.  Industrial pectins: Sources, production and applications , 1990 .

[36]  A. Moes,et al.  Leaching of pectin from mixed pectin/insoluble polymer films intended for colonic drug delivery , 1998 .

[37]  J. Rokem,et al.  In Vitro Evaluation of Calcium Pectinate: A Potential Colon-Specific Drug Delivery Carrier , 1993, Pharmaceutical Research.

[38]  Chen,et al.  Oral particulate delivery: status and future trends. , 1998, Advanced drug delivery reviews.

[39]  J. Fell,et al.  Pectin/chitosan mixtures as coatings for colon-specific drug delivery: an in vitro evaluation , 1998 .

[40]  P. Sinko,et al.  The effect of physical barriers and properties on the oral absorption of particulates. , 1998, Advanced drug delivery reviews.

[41]  J. Sporty,et al.  Pharmacogenomics of drug transporters: the next drug delivery challenge. , 2001, Advanced drug delivery reviews.

[42]  J. Thibault,et al.  Sugar-beet pectins: Chemical structure and gelation through oxidative coupling. , 1986 .

[43]  E. Morris,et al.  Spectroscopic and stoicheiometric characterisation of the calcium-mediated association of pectate chains in gels and in the solid state , 1979 .

[44]  E. Morris,et al.  Conformations and interactions of pectins. II. Influences of residue sequence on chain association in calcium pectate gels. , 1982, Journal of molecular biology.

[45]  B Agoram,et al.  Predicting the impact of physiological and biochemical processes on oral drug bioavailability. , 2001, Advanced drug delivery reviews.

[46]  J. BeMiller An Introduction to Pectins: Structure and Properties , 1986 .

[47]  M. Rafiee-Tehrani,et al.  Peroral delivery systems based on superporous hydrogel polymers: release characteristics for the peptide drugs buserelin, octreotide and insulin. , 2002, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[48]  A. Moes,et al.  Studies of pectin HM/Eudragit RL/Eudragit NE film-coating formulations intended for colonic drug delivery. , 2000, International journal of pharmaceutics.

[49]  L. Miller,et al.  Mode of Action of Pectic Enzymes II. Further Purification of Exopolygalacturonate Lyase and Pectinesterase from Clostridium multifermentans , 1970, Journal of bacteriology.

[50]  R. Kim,et al.  Pharmacogenomics of Drug Transporters , 2003 .

[51]  G. Macleod,et al.  An in vitro investigation into the potential for bimodal drug release from pectin/chitosan/HPMC-coated tablets. , 1999, International journal of pharmaceutics.

[52]  J. Fell,et al.  Hydrogel beads based on amidated pectins for colon-specific drug delivery: the role of chitosan in modifying drug release , 1997 .

[53]  R. Fassihi,et al.  Application of binary polymer system in drug release rate modulation. 2. Influence of formulation variables and hydrodynamic conditions on release kinetics. , 1997, Journal of pharmaceutical sciences.

[54]  M. Rinaudo Physicochemical properties of pectins in solution and gel states , 1996 .

[55]  M. Radomsky,et al.  Sustained-Release Injectable Products , 2000 .

[56]  I. Wilding,et al.  The Use of Scintigraphy to Provide 'Proof of Concept' for Novel Polysaccharide Preparations Designed for Colonic Drug Delivery , 2004, Pharmaceutical Research.

[57]  J. Mcginity,et al.  Influence of processing variables on the properties of free films prepared from aqueous polymeric dispersions by a spray technique , 1995 .

[58]  V. Sinha,et al.  Polysaccharides in colon-specific drug delivery. , 2001, International journal of pharmaceutics.

[59]  J. Nunthanid,et al.  Calcium pectinate gel beads for controlled release drug delivery: II. Effect of formulation and processing variables on drug release. , 1999, Journal of microencapsulation.

[60]  J. Thibault,et al.  Properties of amidated pectins. II. Polyelectrolyte behavior and calcium binding of amidated pectins and amidated pectic acids , 1989 .

[61]  R. Fassihi,et al.  Application of a binary polymer system in drug release rate modulation. 1. Characterization of release mechanism. , 1997, Journal of pharmaceutical sciences.

[62]  J. Fix Oral Controlled Release Technology for Peptides: Status and Future Prospects , 1996, Pharmaceutical Research.

[63]  A. Rubinstein,et al.  In vitro and in vivo analysis of colon specificity of calcium pectinate formulations , 1995 .

[64]  M. Fishman,et al.  Chemistry and function of pectins , 1986 .

[65]  H. Junginger,et al.  Chitosan and its derivatives as intestinal absorption enhancers. , 2001, Advanced drug delivery reviews.

[66]  R Langer,et al.  Responsive polymeric delivery systems. , 2001, Advanced drug delivery reviews.

[67]  J. Fell,et al.  Amidated Pectin Hydrogel Beads for Colonic Drug Delivery-An in vitro Study , 1997 .

[68]  G. Macleod,et al.  Selective drug delivery to the colon using pectin:chitosan:hydroxypropyl methylcellulose film coated tablets. , 1999, International journal of pharmaceutics.

[69]  P. Sriamornsak,et al.  Development of sustained release theophylline pellets coated with calcium pectinate , 1997 .

[70]  K. E. Gabr,et al.  Effect of interpolymer complex formation of chitosan with pectin or acacia on the release behaviour of chlorpromazine HCl , 1993 .

[71]  P. Tso,et al.  From interaction of lipidic vehicles with intestinal epithelial cell membranes to the formation and secretion of chylomicrons. , 2001, Advanced drug delivery reviews.

[72]  K. Amighi,et al.  Effect of pectinolytic enzymes on the theophylline release from pellets coated with water insoluble polymers containing pectin HM or calcium pectinate. , 2000, International journal of pharmaceutics.

[73]  A. Florence,et al.  Particulate delivery: the challenge of the oral route , 1993 .