Enteric delivery of ketoprofen through functionally modified poly(acrylamide-grafted-xanthan)-based pH-sensitive hydrogel beads: Preparation, in vitro and in vivo evaluation

Novel pH-sensitive hydrogel beads were prepared using a hydrolyzed poly(acrylamide-g-xanthan) (PAAm-g-XG) copolymer from a complete aqueous environment and evaluated for targeting ketoprofen to the intestine. The PAAm-g-XG copolymer was synthesized by free radical polymerization under the nitrogen atmosphere followed by alkaline hydrolysis. The copolymer was characterized by FTIR spectroscopy, 1H NMR spectroscopy, elemental analysis and thermogravimetric analysis. Pulsatile swelling study indicated that the copolymer exhibits considerable pH-sensitive behavior unlike pristine xanthan gum. Ketoprofen-loaded pH-sensitive beads were prepared by ionotropic gelation with Al3 + ions. Release of drug from all the copolymeric beads was much lesser than that from pristine xanthan beads. Moreover, a maximum of 20% ketoprofen was released from the copolymeric beads in pH 1.2–5.5 during a period of 3 h, while a major portion of the drug was released in pH 6.8–7.4 gradually over a longer period. Pharmacodynamic activity and stomach histopathology of albino rats indicated that the beads were able to retard the drug release in stomach, and gastric side effects such as ulceration, hemorrhage and erosion of gastric mucosa were diminished when the drug was entrapped into PAAm-g-XG-based pH-sensitive beads.

[1]  K. G. Desai,et al.  Characteristics of vitamin C encapsulated tripolyphosphate-chitosan microspheres as affected by chitosan molecular weight , 2006, Journal of microencapsulation.

[2]  A. Turov,et al.  Poly(vinyl alcohol)-Graft-Polyacrylamide with Different Grafts Number and Length as Studied by 1H NMR Spectroscopy , 2005 .

[3]  H. Kaş,et al.  In vitro and in vivo studies of ibuprofen-loaded biodegradable alginate beads , 2005, Journal of microencapsulation.

[4]  A. K. Anal,et al.  Ionotropic alginate beads for controlled intestinal protein delivery: Effect of chitosan and barium counter-ions on entrapment and release , 2005, Journal of microencapsulation.

[5]  G. Kulkarni,et al.  Development of Controlled Release Spheriods using Natural Polysaccharide as Release Modifier , 2005, Drug delivery.

[6]  A. Pourjavadi,et al.  Modified carrageenan. 5: Preparation, swelling behavior, salt- and ph-sensitivity of partially hydrolyzed crosslinked carrageenan-graft-polymethacrylamide superabsorbent hydrogel , 2004 .

[7]  T. Aminabhavi,et al.  Controlled release of clozapine through chitosan microparticles prepared by a novel method. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[8]  S. Martelli,et al.  Gastro-resistant microspheres containing ketoprofen , 2002, Journal of microencapsulation.

[9]  A. R. Kulkarni,et al.  In-vitro release kinetics of cefadroxil-loaded sodium alginate interpenetrating network beads. , 2001, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[10]  Kinam Park,et al.  Environment-sensitive hydrogels for drug delivery. , 2001, Advanced drug delivery reviews.

[11]  R. Singh,et al.  High performance flocculating agent based on partially hydrolysed sodium alginate-g-polyacrylamide , 2000 .

[12]  M. Saçak,et al.  Graft copolymerization of methyl methacrylate upon gelatin initiated by benzoyl peroxide in aqueous medium , 1999 .

[13]  M. Wirth,et al.  Ketoprofen-poly(D,L-lactic-co-glycolic acid) microspheres: influence of manufacturing parameters and type of polymer on the release characteristics. , 1999, Journal of microencapsulation.

[14]  R. Kinget,et al.  Comparative study on xanthan gum and hydroxypropylmethyl cellulose as matrices for controlled-release drug delivery. II. Drug diffusion in hydrated matrices , 1997 .

[15]  R. Goyal,et al.  Pathogenesis of peptic ulcer disease and current trends in therapy. , 1997, Indian journal of physiology and pharmacology.

[16]  M. R. Aberturas,et al.  Preparation, characterization and in vitro drug release of poly-epsilon-caprolactone and hydroxypropyl methylcellulose phthalate ketoprofen loaded microspheres. , 1996, Journal of microencapsulation.

[17]  Isaac Ghebre-Sellassie,et al.  Multiparticulate Oral Drug Delivery , 1994 .

[18]  J. Plaizier-Vercammen,et al.  Evaluation of Xanthan Cum as a Hydrophilic Matrix for Controlled-Release Dosage form Preparations , 1993 .

[19]  P. R. Chatterji,et al.  Interpenetrating hydrogel networks. 2. Swelling and mechanical properties of the (gelatin-polyacrylamide) interpenetrating networks , 1990 .

[20]  D. Henry.  Side-effects of non-steroidal anti-inflammatory drugs. , 1988, Bailliere's clinical rheumatology.

[21]  P. Brooks.  Side‐effects of non‐steroidal anti‐inflammatory drugs , 1988, The Medical journal of Australia.

[22]  P. Fowler.  Aspirin, Paracetamol and Non-Steroidal Anti-Inflammatory Drugs , 1987, Medical toxicology and adverse drug experience.

[23]  Nicholas A. Peppas,et al.  A simple equation for description of solute release II. Fickian and anomalous release from swellable devices , 1987 .

[24]  Nicholas A. Peppas,et al.  A simple equation for description of solute release I. Fickian and non-fickian release from non-swellable devices in the form of slabs, spheres, cylinders or discs , 1987 .

[25]  Clive G. Wilson,et al.  A comparative study of the gastrointestinal transit of a pellet and tablet formulation , 1984 .

[26]  N. Peppas,et al.  EFFECT OF THE MORPHOLOGY OF HYDROPHILIC POLYMERIC MATRICES ON THE DIFFUSION AND RELEASE OF WATER SOLUBLE DRUGS , 1981 .

[27]  H. Bechgaard,et al.  Controlled-Release Multiple-Units and Single-Unit Doses a Literature Review , 1978 .

[28]  C A WINTER,et al.  Carrageenin-Induced Edema in Hind Paw of the Rat as an Assay for Antiinflammatory Drugs , 1962, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.