(599b) Application of Supercritical Fluid Anti-Solvent Processing to Coat and Disperse a Poorly Soluble Compound On Fast Flo® Lactose

Supercritical CO₂ (SC-CO₂) is used as an anti-solvent for a one-step process which coats a carrier (lactose) with a poorly soluble active pharmaceutical compound, poly vinyl pyrrolidone (PVP) and sodium lauryl sulfate(SDS). The product is a rapidly dissolving, free-flowing powder suitable for direct compression into a tablet dosage form.

In this process, a methanol solution containing the poorly soluble drug, PVP and SDS is sprayed onto a stirred bed of lactose (35 °C, 2000 psig). The rapid uptake of methanol by supercritical CO₂ results in deposition of the Drug, SDS and PVP. X ray powder diffraction results of the Drug/ SDS/ PVP product show that the drug is present in a crystalline form and scanning electron microscopy shows fine drug particles dispersed within the SDS and PVP.

Tablets prepared from the Drug/ SDS/ PVP coated on lactose carrier via SCF process show similar dissolution at the 45 minute time point compared to tablets prepared by a traditional high shear granulation/ fluid bed drying process using jet milled drug and SDS with PVP and lactose. However, the tablets prepared by granulation show a decreasing dissolution over the 90 to 120 minute time period, whereas for the SC-CO₂ process the tablet dissolution is maintained through 120 minutes. For the SC-CO₂ process, the tablet dissolution and the crystal morphology of the drug are unchanged after approximately 16 months storage at room temperature. These data suggest the SCF deposited product can increase the solubility of the drug which could result in increased bioavailability.