pectins and aceclofenac

The aim of this study was to develop a pectin-based colon-specific multiparticulate delivery system. Aceclofenac was used as a model drug owing to its potential therapeutic efficacy in rheumatoid arthritis. Pectin microspheres were prepared using emulsion dehydration technique. These microspheres were coated with Eudragit S-100 using solvent evaporation method. The effect of different variables (polymer, emulsifier, stirring speed and stirring time) was investigated in terms of size, surface morphology, entrapment efficiency, in vitro release and in vivo studies. The size of uncoated microspheres ranged from 30 to 55 µm and exhibited 5-40% of drug release in the upper gastrointestinal tract; however, continuous high release of drug was observed at colonic pH. In addition, the release of drug from the microspheres was found to be higher in the presence of rat cecal contents with maximum release at the 8th hour. This is one of the prerequisites for the effective treatment of rheumatoid arthritis, indicating the effect of colonic enzymes on the pectin microspheres. In vivo studies suggest the maintenance of therapeutic concentration of drug for 24 h with significant anti-inflammatory effect. Therefore, these findings clearly suggest that the Eudragit-coated pectin microspheres offer an exciting mode of aceclofenac delivery to colon in the chronopharmacological treatment of rheumatoid arthritis.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Arthritis, Rheumatoid; Calorimetry, Differential Scanning; Coated Materials, Biocompatible; Delayed-Action Preparations; Diclofenac; Drug Carriers; Drug Chronotherapy; Drug Compounding; Drug Stability; Gastric Juice; Intestinal Secretions; Male; Microspheres; Particle Size; Pectins; Polymethacrylic Acids; Rats; Rats, Wistar; Solubility; Spectroscopy, Fourier Transform Infrared; Surface Properties; Tissue Distribution

The paper describes development of aceclofenac-loaded pectinate-poly(vinyl pyrrolidone) [PVP] beads through ionotropic-gelation. Effects of amount of pectin and PVP on drug encapsulation efficiency (DEE), and cumulative drug release at 6h (R6h) were optimized by using response surface methodology. The optimized beads showed DEE of 96.58 ± 4.15% and R6h of 41.62 ± 2.18% with controlled drug release pattern. FTIR spectroscopy analysis revealed possible intermolecular hydrogen bonding, which could be formed between C=O groups of PVP and -OH groups of pectin in these beads. The swelling of these beads were influenced by pH of the medium.

Topics: Diclofenac; Drug Liberation; Microspheres; Pectins; Povidone

Colonic targeting has gained increasing interest over the past years, not just for the transport of drugs for the treatment of local diseases associated with the colon but also for its potential for transporting peptides and proteins, particularly low molecular weight peptide drugs. Without protection, such peptide drugs are usually digested within the gastric and small intestinal sections. In the present work Layer-By-Layer (LBL) self-assembly was utilized to make Aceclofenac single bilayer microcapsules produced by sequential adsorption of positively charged chitosan and negatively charged Pectin on the external surface of negatively charged Aceclofenac microcrystals. Taguchi approach was applied to determine the best concurrence of composition factors that is concentration of chitosan, pectin, centrifugation speed and incubation time. The microcapsules were characterized for encapsulation efficiency, particle size, zeta potential, scanning electron microscopy and in-vitro release kinetics. Surface electric potential of Aceclofenac microcrystals was found to be negative with zeta potential -1.39 mV, in acetate buffer of pH 4. The primary and the secondary deposit layer of chitosan and pectin was found to have a positive and negative charge with zeta potential of +5.57 mV and -22.8 mV respectively. The sequential changing of surface zeta potential after each deposition is a satisfactory indication of the LBL self-assembly of the oppositely charged polyelectrolytes. The average size and encapsulation efficiency of the optimized single bilayer microcapsules (F5) was found to be 20µm and 63.83%, respectively. The ex-vivo percentage cumulative drug release of (F5) in Phosphate buffer pH 6.8 containing 2-4% w/v colonic fecal matter of male albino rat was found to be 98.40%. The optimized batch of microcapsules showed first order release kinetics (R(2)= 0.950) in presence of colonic fecal matter.

Topics: Animals; Biological Availability; Chitosan; Delayed-Action Preparations; Diclofenac; Drug Compounding; Feces; Hydrogen-Ion Concentration; Male; Microscopy, Electron, Scanning; Particle Size; Pectins; Polymethacrylic Acids; Rats; Rats, Inbred Strains; Static Electricity; Surface Properties

Ionotropic gelation was used to entrap aceclofenac into algino-pectinate bioadhesive microspheres as a potential drug carrier for the oral delivery of this anti-inflammatory drug. Microspheres were investigated in vitro for possible sustained drug release and their use in vivo as a gastroprotective system for aceclofenac. Polymer concentration and polymer/drug ratio were analyzed for their influence on microsphere properties. The microspheres exhibited good bioadhesive property and showed high drug entrapment efficiency. Drug release profiles exhibited faster release of aceclofenac from alginate microspheres whereas algino-pectinate microspheres showed prolonged release. Dunnet's multiple comparison analysis suggested a significant difference in percent inhibition of paw edema when the optimized formulation was compared to pure drug. It was concluded that the algino-pectinate bioadhesive formulations exhibit promising properties of a sustained release form for aceclofenac and that they provide distinct tissue protection in the stomach.

Topics: Adhesiveness; Administration, Oral; Alginates; Animals; Anti-Inflammatory Agents, Non-Steroidal; Delayed-Action Preparations; Diclofenac; Disease Models, Animal; Drug Carriers; Edema; Glucuronic Acid; Hexuronic Acids; Inflammation; Male; Microspheres; Pectins; Rats; Rats, Wistar; Stomach