Processing triacetyl-β-cyclodextrin in the liquid phase using supercritical CO₂

TA-β-CD has been proposed as an effective sustained release carrier for highly water soluble drugs with short biological half-lives. In this work, the possibility of preparing drug - triacetyl-β-cyclodextrin (TA-β-CD) complexes in the liquid phase by exploring its solid-liquid-gas equilibrium (S-L-G) under supercritical CO₂ atmosphere was evaluated. The S-L-G equilibrium line for the binary system TA-β-CD + CO₂ was determined by a visual method for pressures up to 25.3 MPa. At the studied conditions, a homogeneous and translucent liquid phase emerge at 307 K when exposed to CO₂ pressurized at 16 MPa and this temperature further increases with increasing pressure, up to 318 K at 25.3 MPa. The S-L-G equilibrium behaviour observed is typical of this kind of asymmetric systems, it is totally CO₂ density-dependent and opens the possibility of further processing TA-β-CD in the liquid phase. In order to investigate the possibility of preparing a drug-TA-β-CD complex in the liquid phase of TA-β-CD, a preliminary experiment was performed at 25 MPa and 308 K using flufenamic acid (FA) as the model active principle.