Amorphous-Amorphous Phase Separation in Polymeric API Systems

Polymer/API systems are capable of increasing the bioavailability of poorly water soluble drugs. Recently, this technology was applied in numerous products to increase and control the dissolution in the gastrointestinal tract [1]. Such systems are therefore highly relevant in pharmaceutical industry. Knowing the phase behavior is crucial for the design of a long-term stable formulation. The solubility of APIs in polymeric carriers has recently been investigated [2] and can be considered in the screening process searching for long-term stable formulations. Besides crystallization, amorphous-amorphous phase separation might occur during storage or processing leading to an API-rich and an API-poor phase. Amorphous-amorphous phase separation is reported only for few systems so far [1]. A systematic and thermodynamic investigation of this phenomenon is not available so far. Amorphous-amorphous phase separation in API-polymer formulations particularly occurs when exposed to high relative humidity. The water uptake of a formulation accelerates API recrystallization and thereby decreasing the thermodynamic stability. This phenomenon is elucidated experimentally for spray- dried formulations by DSC, PXRD and Raman microscopy and thermodynamically modeled using the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT)[3].