(83d) Crystalline Particle Formation and Polymorphism From Uniform Droplet Evaporation

Particle size, shape and structure are all important product qualities with direct implications for the pharmaceutical, food product and dye industries.  Crystal size directly impacts dissolution rate. Crystal shape affects both downstream processes such as filtering, washing and drying as well as material properties such as mechanical strength, bioavailability and surface functionality.  Finally, different crystal structures, or polymorphs, impact the entire scope of the product from melting point and solubility to patent considerations.  Thus, methods to manipulate and control size, shape and structure are continuously being sought.  Droplet evaporation, commonly used industrially through spray drying, offers some advantages such as a reduction in production steps when compared to traditional crystallizations; however, it is notoriously difficult to control and model the product properties because of the varied droplet sizes and flow patterns of the droplets.  Monodisperse droplet generation offers a useful tool for better controlling droplet evaporation by eliminating the challenges associated with droplet size distributions in spray dryers.  Monodisperse droplet generators have previously been used to produce uniform particle sizes (Nandiyanto and Okuyama 2011, Vehring 2008); however, crystalline properties have not been the primary focus of previous work.

In this talk, we will highlight our recent work on producing crystalline particles through the evaporation of monodisperse droplets produced using a vibrating orifice aerosol generator (VOAG).  In this study, we use succinic acid as a test case molecule.  The experiments show that we not only can produce monodisperse particle sizes, but that our particles are also fully crystalline, containing no amorphous characteristics.  As with other crystallization methods, solvent choice is a key variable in determining the morphology of the resulting particles, and we demonstrate the variability in morphology across several solvents (e.g. acetone, water, isopropanol).  We will show that solvent choice indeed impacts the morphologies of these particles and demonstrate that the morphologies fall into a new class of particle shapes that previously have not been obtained from droplet evaporation.  Additionally, we will show that the polymorphs obtained through this method are unique when compared to the crystallization of succinic acid from bulk solution.  Finally, we will discuss the potential for this type of droplet evaporation as a tool for studying polymorphism of organic molecules in general and as a good system to develop fundamental models that could later be applied to industrial scale processes such as spray drying.

References

Nandiyanto, A. B. D.; Okuyama, K. Adv. Powder Technol. 2011, 22, 1-19.

Vehring, R. Pharm. Res. 2008, 25, 999-1022.