Enhancement of dissolution rate of poorly-soluble active ingredients by supercritical fluid processes. Part I: Micronization of neat particles.

In this first of two articles, we discuss some issues surrounding the dissolution rate enhancement of poorly-soluble active ingredients micronized into nano-particles using several supercritical fluid particle design processes including rapid expansion of supercritical solutions (RESS), supercritical anti-solvent (SAS) and particles from gas-saturated solutions/suspensions (PGSS). Experimental results confirm that dissolution rates do not only depend on the surface area and particle size of the processed powder, but are greatly affected by other physico-chemical characteristics such as crystal morphology and wettability that may reduce the benefit of micronization.

Enhancement of dissolution rate of poorly soluble active ingredients by supercritical fluid processes. Part II: Preparation of composite particles.

In this second of two articles, we show that several supercritical processes have been developed to prepare composite particles of poorly soluble active ingredients. Microencapsulation, cyclodextrin inclusion and impregnation allow to incorporate poorly soluble materials in fast-dissolving hydrophilic excipients, leading to promising results in terms of dissolution rate enhancement.

Enzymatic reaction kinetic: comparison in an organic solvent and in supercritical carbon dioxide.

Myristic acid esterification has been performed by an immobilized lipase from Mucor Miehei both in n-hexane and in supercritical carbon dioxide (SCCO(2)). The enzyme is stable in SCCO(2) at 15 MPa and 323 K. The reaction rate is influenced by the concentration of water and by the reaction medium composition. A reaction mechanism is proposed, and kinetic parameters are determined at 12.5 MPa and 313 K. Maximum velocity appears 1.5-fold higher in SCCO(2) than in n-hexane; however, as solubility of myristic acid is greater in n-hexane, it is not yet definitively clear that the supercritical medium is more favorable than the classical organic solvent for this type of enzyme reaction.