New methods for preparing cyclodextrin inclusion compounds. II. Effects of heating temperature, water content and drug properties on the inclusion formation.

Abstract

Inclusion compounds were prepared by heating mixtures of a drug and α-cyclodextrin (α-CD) hydrate in a sealed container. Inclusion formation was studied as a function of heating temperature, water content of α-CD and drug properties, using powder X-ray diffraction, infrared spectroscopy, and differential scanning calorimetry. Drug molecules were included in α-CD molecules by heating above 80°C in ampules. Inclusion compounds were prepared with six different drugs. The rates of inclusion formation were well correlated with the vapor pressures of the drugs, that is, higher vapor pressure of drugs resulted in faster inclusion compound formation. It was revealed that the heating temperature, water content of α-CD, and vapor pressure of the drug are important parameters affecting the formation of inclusion compounds by the heating method.