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Factors influencing the mechanism of release from sustained release matrix pellets, produced by extrusion/spheronisation

Tapia, C; Buckton, G; Newton, JM; (1993) Factors influencing the mechanism of release from sustained release matrix pellets, produced by extrusion/spheronisation. International Journal of Pharmaceutics , 92 (1-3) 211 - 218. 10.1016/0378-5173(93)90282-K.

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Abstract

Spheres have been prepared from a wet mass by extrusion and spheronisation. Chitosan was included as a solution in the powder mix. Four formulations were considered, containing two different concentrations of chitosan, each prepared at two different sizes of sphere; either approx. 1 or 2 mm. The release of a model drug (diclofenac sodium) from the spheres was found to be considerably slower than formulations without added chitosan (i.e. ca. 100% in 6 h, rather than 30 min). Thus it is possible to retard drug release from a sphere, without the need for polymer coating, by use of a hydrophilic gel. The drug release profiles followed first order kinetics (for all four systems), and produced a straight line when plotted as a function of the square root of time. A straight line was also obtained when a double logarithmic plot of release as a function of time was prepared, the gradient of which was in the order of 0.5, this would indicate Fickian diffusion, if from a thin slab, but as the release was from a sphere, the process was described as fitting a non-Fickian diffusion model. Dissolution testing at different stirring speeds did not alter the rate of drug release, demonstrating that the diffusion process was controlled within, rather than in the layer of fluid around, the sphere. Thermodynamic activation parameters were calculated and the four formulations were compared by compensation analysis. It was apparent that there was no common mechanism for drug release, but that the concentration of the Chitosan related to the enthalpy change, and the Gibbs free energy change correlated with the dissolution rate.

Type:Article
Title:Factors influencing the mechanism of release from sustained release matrix pellets, produced by extrusion/spheronisation
DOI:10.1016/0378-5173(93)90282-K
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics
UCL > School of BEAMS > Faculty of Engineering Science > Mechanical Engineering

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