| The primary goal of crystallization process is to fabricate particles with controlled size, shape and polymorph, and desired chemical purity. These individual characteristics can affect the physical and chemical properties of the solid. In this work, two molecular level strategies: templated-nucleation via self-assembled monolayers (SAMs) and the use of structurally related impurities as inhibitors, are employed to control the crystallization process. In the first method, organized organic assemblies namely SAMs, act as catalysts for nucleation of molecular crystals. The nanoengineered surfaces can modify the crystal habit as well as lead to preferred crystal orientation. Furthermore, the well-defined template can be used to direct the nucleation of different polymorphs. Results show that on 2-mercaptoethanol SAMs on gold, alpha- and beta-glycine concomitantly nucleated while on the other functionalized surfaces, only the alpha-form is exclusively formed. An interesting feature of SAMs is that these surfaces can be precisely positioned, thus, allowing the formation of patterned surfaces. Making use of the contrasting wetting properties (hydrophilic/hydrophobic regions), crystallization can be confined to the hydrophilic regions as immersing and slowly withdrawing a patterned substrate from solution leads to the creation of array of solution drops. Crystallization can occur as a result of solvent evaporating from the droplets. This approach provides a viable method to fabricate particles in a controlled manner and size.; The second method to control the crystallization outcome is through the use of tailor-made impurities. The influence of structurally related impurities on the solution-mediated phase transformation of the metastable A form of an active pharmaceutical ingredient to the stable B form is investigated in 2-propanol. The transformation behavior is quantified using powder X-ray diffraction. It is observed that the rate of transformation is sensitive to the impurities and that the presence of certain inhibitors reduces the rate of transformation. Concurrently molecular modeling studies are undertaken to investigate the incorporation of these structurally related impurities into the crystal lattice, and it is observed that the build-in approach used in morphology predictions for additive-host systems can be applied to evaluate the extent of impurity incorporation. |
