Characterization of Dextromethorphan And Dextrorphan Uptake by a Putative Glutamic Acid Carrier and Passive Diffusion Across Brain Microvessel Endothelium

Read More: http://informahealthcare.com/doi/abs/10.3109/10717549309022764The mechanisms of uptake and transcellular passage of dextromethorphan (DM) and its major metabolite dextrorphan (DX) across the endothelial component of the blood–brain barrier have been investigated with primary cultures of bovine brain microvessel endothelial cells (BMECs). The uptake of [14C]DM and [14C]DX by BMECs was observed to be temperature-sensitive and saturable, with approximate Km's of 0.12 and 0.29 mM and Vmax's of 9.2 and 11.0 pmol/mg/min, respectively. The BMEC uptake of [14C] DM was inhibited half-maximally by approximately 0.57 mM L-glutamic acid, 0.71 mM N-methyl-d-asparatate (NMDA), and 0.99 mM DL-threo-β-hydroxyaspartic acid. The BMEC uptake of [14C]DX was inhibited half-maximally by approximately 0.48 mM L-glutamic acid, 1.50 mM NMDA, and 0.69 mM DL-threo-β-hydroxyaspartic acid. Conversely, the bidirectional passage of DM and DX across confluent BMEC monolayers occurred at a faster rate but was neither saturable nor inhibited by high concentrations of glutamic acid, NMDA, or unlabeled DM or DX. These results suggest that DM and DX are capable of interacting with a low-capacity glutamic acid-type carrier mechanism on the apical surface of BMECs. However, the net transfer of these agents across BMEC monolayers appeared to be more rapid and passive in nature

Amorphous Solid DispersionsTheory and Practice /

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Influence of an Acrylic Polymer Blend on the Physical Stability of Film-Coated Theophylline Pellets

The purpose of this study was to investigate the physical stability of a coating system consisting of a blend of two sustained release acrylic polymers and its influence on the drug release rate of theophylline from coated pellets. The properties of both free films and theophylline pellets coated with the polymer blend were investigated, and the miscibility was determined via differential scanning calorimetry. Eudragit® RS 30 D was plasticized by the addition of Eudragit® NE 30 D, and the predicted glass transition temperature (Tg) of the blend was similar to the experimental values. Sprayed films composed of a blend of Eudragit® NE 30 D/Eudragit® RS 30 D (1:1) showed a water vapor permeability six times greater than films containing only Eudragit® NE 30 D. The presence of quaternary ammonium functional groups from the RS 30 D polymer increased the swellability of the films. The films prepared from the blend exhibited stable permeability values when stored for 1 month at both 25°C and 40°C, while the films which were composed of only Eudragit® NE 30 D showed a statistically significant decrease in this parameter when stored under the same conditions. Eudragit® NE 30 D/Eudragit® RS 30 D (1:1)-sprayed films decreased in elongation from 180% to 40% after storage at 40°C for 1 month, while those stored at 25°C showed no change in elongation. In coated pellets, the addition of Eudragit® RS 30 D to the Eudragit® NE 30 D increased the theophylline release rate, and the pellets were stable when stored at 25°C for a period of up to 3 months due to maintenance of the physico-mechanical properties of the film. Pellets stored at 40°C exhibited a decrease in drug release rate over time as a result of changes in film physico-mechanical properties which were attributed to further coalescence and densification of the polymer. When the storage temperature was above the Tg of the composite, instabilities in both drug release rate and physical properties were evident. Stabilization in drug release rate from coated pellets could be correlated with the physico-mechanical stability of the film formulation when stored at temperatures below the Tg of the polymer