| Supercritical fluid technology, specifically rapid expansion of supercritical solutions (RESS) has been used to develop delivery systems with enhanced drug dissolution rates. Unlike traditional solvent-based processes using organic solvents, and in which residues can remain in the final products, RESS processing, which is also a solvent-based process, uses a relatively safe and environmentally acceptable solvent, supercritical carbon dioxide that is easily, and completely, removed. Two structurally similar local anesthetic drug models were studied: lidocaine, which is relatively insoluble, and ropivacaine, which is classified as insoluble. The delivery systems consisted of submicrometer sized particles of drug, and similar small particles of solid dispersions, including microcrystalline dispersions, solid solutions, and solid glasses. Particle size reduction by RESS processing produces small particles of relatively uniform sizes and shapes. Release of drug in vitro increased from about 78% to 86%, and 11% to 25%, at the end of three hours, for lidocaine and ropivacaine, respectively. By contrast, complete release of lidocaine occurred within three hours from small particles of lidocaine-PEG 8000 solid dispersions containing 10% to 80% w/w lidocaine. A more complex, but desirable pattern of drug release under certain clinical situations resulted from small particles of lidocaine-ropivacaine solid dispersions and/or solid solutions. At 20%, 50% or 80% w/w lidocaine, rapid release of lidocaine occurred initially and was complete within about 3 hours. Parallel was release of ropivacaine, which did not give a comparable initial burst of drug; but rather, an essentially steady release that lasted for about 8 hours. These types of systems therefore provided an initial rapid release of one drug, which was the more soluble, and sustained release of the other. Dissolution rate enhancement appears to occur from increases in the total surface areas of the various drug and drug-containing compositions. For the solid dispersions, the effect of particle size reduction was accompanied by apparent increases in the effective surface areas from improved wetting of the particles. There was also another important contributing factor, a decreased tendency of the small particles to aggregate due to the presence of the more soluble component, i.e., polyethylene glycol 8000 or lidocaine. |
