Phase Behavior of Potential Drug Delivery Systems, Polycaprolactone─Nonsteroidal Anti-Inflammatory Drug in a Pressurized Carbon Dioxide Medium

Although high-pressure technologies are widely used, for example, in the polymer and pharmaceutical industries, measuring phase equilibria in high-pressure media is still challenging, especially for multicomponent systems. Although the most reliable methods in solid-liquid-(-gas) equilibrium measurements, also providing additional information, are high-pressure differential scanning calorimetry (DSC) and transitiometry, the most common techniques for detecting solid-liquid phase transitions in pressurized media are visual observation-based methods. In this research, the melting behavior of potential controlled-release active pharmaceutical ingredient (API) polymer systems (ibuprofen-polycaprolactone, ketoprofen-polycaprolactone) in the presence of high-pressure carbon dioxide was investigated. First, the pressure-dependent behavior of pure compounds was investigated by using two different methods. One is based on differential pressure measurement, developed by the research group, and the other is the widely used visual observation-based process. The API polymer systems were investigated in a high-pressure view-cell. Both systems showed eutectic behavior. According to the measurement data, eutectic and melting temperatures of the system were highly dependent on pressure, but the eutectic composition was found to occur at a nearly constant value. The thermodynamic data from the research could be applicable to high-pressure particle formation technologies, such as the particle from gas saturated solutions (PGSS).