(315b) Subcritical Water as a Novel Fluid for Pharmaceutical Processing and Drug Delivery Formulation

Subcritical water has potential as a green fluid for the processing of drug formulations. Subcritical water has been used extensively in hydrolysis based extraction processes and reverse phase high performance liquid chromatography as a mobile carrier. Chromatographic applications capitalize on the temperature induced polarity changes and decreased elution times associated with high temperature operations. Appropriate manipulation of water polarity via temperature changes allows for the dissolution of materials that are regarded as water insoluble at ambient conditions in subcritical water. Examples of pharmaceutically active hydrophobic compounds that have been solubilised in water under subcritical conditions include paracetamol, methotrexate, and acetylsalicylic acid. For the water to exhibit values of the dielectric constant similar to commonly used solvents ? i.e. methanol and acetone- temperatures between 160 and 240oC are required, which cause concerns about the occurrence of thermal degradation. However several pharmaceutically active compounds are stable under these conditions in subcritical water and can thus be processed. In order to explore the full potential of subcritical water as a processing medium in the manufacturing of particle engineered bioactives and polymer composites for controlled delivery of drugs; the solubilities of various biocompatible polymers and bioactive compounds in subcritical water are investigated. The results are discussed in light of the development of appropriate processing methods.