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      In vitro and in vivo evaluation of fenofibrate solid dispersion prepared by hot-melt extrusion

      , ,
      Drug Development and Industrial Pharmacy
      Informa UK Limited

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          Abstract

          This article aimed to develop fenofibrate solid dispersion with high bioavailability using hot-melt extrusion and compare the difference of Eudragit E100 and polyvinylpyrrolidone-vinyl acetate copolymer S630 (PVP-VA) in dissolution.

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          Most cited references24

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          Solubility parameters as predictors of miscibility in solid dispersions.

          This paper reports interactions and possible incompatibilities in solid dispersions of hydrophobic drugs with hydrophilic carriers, with solubility parameters employed as a means of interpreting results. Systems containing ibuprofen (IB) and xylitol (XYL) in varying proportions and systems of IB with other sugars and a sugar polymer were produced using solvent evaporation and fusion methods. Additionally, bridging agents were employed with IB/XYL systems to facilitate the production of a solid dispersion. Results show that IB formed no interactions with any of the sugar carriers but interacted with all the bridging agents studied. The bridging agents were immiscible with XYL in the liquid state. Results of other reported drug/carrier systems and those from the systems studied in this paper were interpreted using Hildebrand solubility parameters. A trend between differences in drug/carrier solubility parameters and immiscibility was identified with incompatibilities evidence when large solubility parameter differences exist between drug and carrier. It was concluded that Hildebrand parameters give an indication of possible incompatibilities between drugs and carriers in solid dispersions, but that the use of partial solubility parameters may provide a more accurate prediction of interactions in and between materials and could provide more accurate indications of potential incompatibilities.
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            Physicochemical properties and mechanism of drug release from ethyl cellulose matrix tablets prepared by direct compression and hot-melt extrusion.

            The objective of this research project was to determine the physicochemical properties and investigate the drug release mechanism from ethyl cellulose (EC) matrix tablets prepared by either direct compression or hot-melt extrusion (HME) of binary mixtures of water soluble drug (guaifenesin) and the polymer. Ethyl cellulose was separated into "fine" or "coarse" particle size fractions corresponding to 325-80 and 80-30 mesh particles, respectively. Tablets containing 30% guaifenesin were prepared at 10, 30, or 50 kN compaction forces and extruded at processing temperatures of 80-90 and 90-110 degrees C. The drug dissolution and release kinetics were determined and the tablet pore characteristics, tortuosity, thermal properties and surface morphologies were studied using helium pycnometry, mercury porosimetry, differential scanning calorimetry and scanning electron microscopy. The tortuosity was measured directly by a novel technique that allows for the calculation of diffusion coefficients in three 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. The release rate was shown to be dependent on the ethyl cellulose particle size, compaction force and extrusion temperature.
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              Characterization of cellulosic hot-melt extruded films containing lidocaine.

              Hot-melt extrusion technology was used to produce thin films containing a model drug, lidocaine, and the cellulosic polymers hydroxypropyl cellulose (HPC) and hydroxypropyl methyl cellulose (HPMC). Two film formulations were extruded and compared, one containing only HPC and the other containing HPC:HPMC (80:20). Thermal analysis of the films using differential scanning calorimetry (DSC) suggested that the drug existed in the amorphous condition, which was confirmed by wide angle X-ray diffractometry. Sustained release of the drug was observed from both of the polymer matrices. Dissolution profiles suggested that HPMC retarded the drug release from HPC:HPMC (80:20) films. However, the mechanism of drug release from both of the films was predominantly diffusion of the drug through the polymer matrices. Incorporation of HPMC also increased both adhesive strength and work of adhesion as compared to the HPC-only films.
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                Author and article information

                Journal
                Drug Development and Industrial Pharmacy
                Drug Development and Industrial Pharmacy
                Informa UK Limited
                0363-9045
                1520-5762
                December 03 2009
                June 2010
                February 06 2010
                June 2010
                : 36
                : 6
                : 681-687
                Article
                10.3109/03639040903449720
                20136483
                0ffd3a46-34b3-49e5-8ce1-013320081b3d
                © 2010
                History

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