Unique Polymorph Formation and Its Effects on Pharmaceutical Science

Unique Polymorph Formation and Its Effects on Pharmaceutical Science

 

2015 AIChE Annual Meeting

 

Victoria Karakis and Dr. Ryan C. Snyder

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 material to exist in more than one crystal structure is called polymorphism. Polymorphism is extremely important in pharmaceutical development for a variety of reasons. Less stable or 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 polymorph space before manufacturing pharmaceuticals to avoid future issues with either production or patents. Thus, methods to identify polymorphs are critical for success. In this work, we utilize a process of monodisperse droplet evaporation technology to form polymorphs 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 metastable polymorphs. In this research, dicarboxylic acids including succinic, glutaric, and suberic acid are utilized as the solute or model pharmaceutical ingredient. In order to investigate the morphology and polymorphism of the particles, Scanning Electron Microscopy (SEM) and X-Ray Diffraction (XRD) are used respectively. In this work, we will present the formation of metastable polymorphs of succinic, suberic and glutaric acid at conditions far from previous work. Additionally, a previously undiscovered polymorph of suberic acid is presented. Thus, this work demonstrates the use of the VOAG as an effective method to investigate polymorphism.