Physicochemical and mechanical characterization of hot-melt extruded dosage forms

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Crowley, Michael McDonald

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The physicochemical and mechanical properties and the mechanisms of drug release from drug delivery systems prepared by hotmelt extrusion were investigated. The influence of processing conditions and the thermal properties of the polymeric retardants was also studied. The stability of polyethylene oxide (PEO) in sustained release tablets prepared by hot-melt extrusion was investigated. The chemical stability of PEO was found to be dependent on the storage and processing temperature, the screw speed and the molecular weight of the polymer. Lower molecular weight PEO MW = 100,000 (PEO 100K) was demonstrated to be a suitable processing aid for PEO 1M. Vitamin E, Vitamin E Succinate and Vitamin E TPGS were found to be suitable stabilizers for PEO; however, ascorbic acid was shown to degrade the polymer in solution. Drug release rates from hot-melt extruded tablets stabilized with antioxidants were found to be dependent on the hydrophilic nature of the antioxidant. The physicochemical properties and mechanism of drug release from ethyl cellulose matrix tablets containing a water soluble drug (guaifenesin) were investigated. Tablets were prepared by direct compression and hot-melt extrusion techniques. The drug dissolution and release kinetics were determined and the tablet pore characteristics, tortuosity, thermal properties and surface morphologies were studied. The tortuosity was measured directly by a novel technique that allows for the calculation of diffusion coefficients in 3 experiments. The Higuchi diffusion model, percolation theory and polymer free volume theory were applied to the dissolution data to explain the release properties of drug from the matrix systems. Films containing PEO and two model drugs (guaifenesin and ketoprofen) were prepared by hot-melt extrusion. Both guaifenesin and ketoprofen were stable during the extrusion process. Wide angle X-ray diffraction suggested that guaifenesin crystallized from the melt upon cooling, but ketoprofen formed a solid solution. Crystallization of guaifenesin on the surface of the film could be observed using scanning electron microscopy at all concentrations studies, but did not reveal ketoprofen crystallization until reaching the 15% level. Guaifenesin and ketoprofen were found to decrease the drive load, increase the stability of polyethylene oxide and plasticize the polymer during extrusion. The percent elongation decreased with increasing guaifenesin concentrations, but increased with increasing ketoprofen concentrations. Both guaifenesin and ketoprofen decreased the tensile strength of the film.