Crystal Engineering for Product and Process Design

Crystalline organic solids are ubiquitous as either final products or as intermediates in the specialty chemical, pharmaceutical, and home & personal care industries. Virtually all small molecular weight drugs are isolated as crystalline materials, and over 90% of all pharmaceutical products are formulated in particulate, generally crystalline form. Crystalline chemical intermediates, such as adipic acid, are produced in large amounts to make polymers and specialty products. Skin creams and other personal care product formulations contain crystalline solids. Solution crystallization is the most common operation in these industries for the separation and purification of products that are solids at room temperature and pressure. During crystallization, many physico-chemical characteristics of the substance are defined, including crystal polymorph, shape and size, chemical purity and stability, bioavailability, solubility and dissolution rate. In most cases the properties of the crystalline solid have a major impact on the functionality of the final product as well as the design and operation of the manufacturing process, and in most cases the two cannot be considered separately. Selection and manipulation of crystal shape and size for organic materials has been a long term objective of many crystal growers in both industry and academia. In recent years, the additional objective of selecting and maintaining the crystal polymorph has joined this list of critically important attributes that need to be controlled, especially for pharmaceutical products. The ability of a compound with a distinct internal crystal structure to crystallize in various shapes and polymorphs is related to the underlying solid state physics