In order to effectively deliver an Active Pharmaceutical Ingredient (API), pharmaceutical companies rely on specific particle properties including size, morphology, and structure to achieve the desirable drug performance. The ability of a solid to exist in more than one arranged crystal structure is called polymorphism. When polymorphism exists for a given compound, there is typically one stable polymorph and one or more less stable or metastable polymorphs at a given temperature and pressure. Alternatively, amorphous solids, solids without an ordered structure, are inherently less stable and can be induced with the help of an excipient. Less stable amorphous structures and metastable polymorphic structures typically crystallize first, followed by rapid recrystallization into the stable form. Methods can be used to preserve less stable structures by preventing the rapid transformation. However, the length of time these less stable structures are maintained for before they transition to the more stable structure is less defined. Internal structure is extremely important in pharmaceutical development for a variety of reasons. Less stable amorphous structures and metastable polymorphic structures are more soluble in the body and therefore have a higher level of bioavailability, the fraction of drug that dissolves appropriately in the patient and is delivered to the system to provide relief of symptoms. Also, it is important to know the entire polymorphic space before manufacturing pharmaceuticals to avoid future issues with either production or patents. In addition, the phase transformation from one polymorph to another can dictate drug shelf life. Thus, methods to identify and understand polymorphs are critical for success. In this work, we utilize a process of monodisperse droplet evaporation technology to form and further investigate less stable structures that are not obtained with identical chemistry using other formation processes.
Monodisperse droplet evaporation technology is implemented via the Vibrating Orifice Aerosol Generator (VOAG), which creates droplets of solution that are well dispersed from one another allowing for the solvent to rapidly evaporate. The rapid evaporation in the VOAG leads to high supersaturations, which drives a potential for formation of less stable structures. In this research, suberic acid is utilized as the solute or model pharmaceutical ingredient. In order to investigate the morphology, Scanning Electron Microscopy (SEM) is used. X-Ray Diffraction (XRD) and Differential Scanning Calorimetry (DSC) are used to analyze structure and understand phase transformation kinetics. In this work, we will present the formation of amorphous and metastable structures of suberic acid at conditions far from previous work. In addition, we will present the phase transformation kinetics of amorphous and metastable suberic acid. Thus, this work demonstrates the use of the VOAG as an effective method to investigate polymorphism.
