Supercritical fluid technology, specifically the method of rapid expansion of supercritical solutions (RESS), has been used to prepare small particles consisting of solid solutions of a relatively insoluble drug and a water-soluble excipient. With an increasing number of relatively insoluble compounds being discovered, a general process for enhancing drug dissolution rates would assist formulation of these compounds for therapeutic use. Solid solutions could serve as a means for enhancing drug dissolution rates, since the drug is dispersed in a solid solvent in its smallest form, i.e., a molecule, prior to entering into solution. Therefore, solid solutions consisting of the relatively insoluble model drugs lidocaine or probucol and a water-soluble surfactant, poloxamers 407, 188, or 403 were prepared by RESS processing. Dissolution studies of these systems were performed and evaluated for their ability to enhance drug release rates. Furthermore, the mechanism by which solid solutions form in these systems was determined using differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy. Scanning electron microscopy (SEM) was also used to study the surface characteristics of these particulate systems.

Dissolution studies of these particles showed an enhanced rate of release of drug in the presence of poloxamer. This enhancement was due to the apparent formation of solid solutions. In addition, poloxamers served to improve the wettability of the drug particles by reducing the interfacial tension and contact angle at the solid/liquid interface, thereby helping enhance the dissolution rate of the drug. DSC of these particulate systems indicated the formation of solid solutions of drug and poloxamer with increasing proportion of poloxamer. At the point where all of the drug is molecularly dispersed forming a solid solution, no endotherm for the drug appears on the DSC thermogram. Therefore, in a phase diagram, linear extrapolation of the enthalpies of drug as functions of mole fraction to zero enthalpy could serve as a novel means for predicting the mole fraction of drug at which a solid solution should form. With the formation of solid solutions, hydrogen bonding occurred between the drug and poloxamer. This bonding was dependent on the polyoxyethylene chain length of the three poloxamers, i.e., where hydrogen bonding primarily occurs. Solid solutions formed for systems consisting of drug and poloxamers 407 or 188, which have similar polyoxyethylene lengths and hence similar amounts of available sites for bonding. Solid solutions however did not form for systems consisting of drug and poloxamer 403 since poloxamer 403 has approximately half the polyoxyethylene length of poloxamers 407 and 188. Lastly, SEM shows the formation of small particles that vary in appearance as functions of poloxamer concentration, i.e., from smooth spherical surfaces to structures similar to those of the drug alone.