The interest in hot-melt extrusion (HME) as a drug delivery technology for the production of glass solutions is growing rapidly. HME glass solutions have a tendency to recrystallize during storage and also typically have a very dense structure, restricting the ingress of dissolution fluid and retarding drug release. In this study, we have used HME to manufacture glass solutions containing celecoxib (CX) and polyvinylpyrrolidone (PVP) and have assessed the use of supercritical carbon dioxide (scCO2) as a pore-forming agent to enhance drug release. Differential scanning calorimetry confirmed the formation of glass solutions following extrusion. All extrudates exhibited a single glass transition temperature (Tg), positioned between the Tg values of CX and PVP. The instability of glass solutions is a significant problem during storage. Stabilization may be improved through the appropriate choice of excipient to facilitate drug–polymer interactions. The Gordon–Taylor equation showed that the Tg values of all extrudates expected on ideal mixing were lower than those observed experimentally. This may be indicative of drug–polymer interactions that decrease free volume and elevate the Tg. Molecular interactions between CX and PVP were further confirmed using Fourier transform infrared and Raman spectroscopy. Storage stability of the extrudates was shown to be dependent on drug loading. Samples containing a higher CX loading were less stable, which we ascribed to decreased Tg and hence increased mobility within the drug–polymer matrix. The solubility of CX was improved through the formulation of extruded glass solutions, but release rate was relatively slow. Exposure of extrudates to scCO2 had no effect on the solid-state properties of CX but did produce a highly porous structure. The drug-release rate from extrudates after scCO2 exposure was significantly higher.

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Pressure drop in small orifices (8–109 μm) is examined by comparing the experimental data of Hasegawa, Suganuma, and Watanabe [Phys. Fluids 9, 1 (1997)] with theoretical and numerical solutions of the Navier–Stokes equations in order to test the claim by Hasegawa, Suganuma, and Watanabe that the data could not be explained by traditional continuum mechanics. The Reynolds number varies from zero (for the theoretical solution to Stokes flow) to 1000. The ratio of the orifice thickness to its diameter varies from 0.092 to 1.14. The primary increase in pressure drop is shown to be due to the effect of a finite thickness of the orifice, and this effect is predicted for Stokes flow by the theory of Dagan, Weinbaum, and Pfeffer [J. Fluid Mech. 115, 505 (1982)]. Numerical results presented here agree with Dagan, Weinbaum, and Pfeffer at Reynolds numbers below 10 and with the experimental data of Hasegawa, Suganuma, and Watanabe for low and intermediate Reynolds numbers. Most of the data can be predicted using traditional continuum mechanics.

The plasticizing effect of supercritical CO2 (scCO2) during the extrusion of polymers was investigated. A modified extrusion system was used to demonstrate the viscosity‐reducing effect of scCO2 together with a capability to produce foam‐free extrudate with selected polymers, including poly(vinyl chloride). Samples of extrudate and materials prepared off‐line by using a pressure vessel were characterized by thermal, mechanical, and X‐ray techniques. After gas diffusion from the polymer, there was no long‐term effect on polymer structure and properties. J. VINYL ADDIT. TECHNOL., 2008. © 2008 Society of Plastics Engineers.