Non-ambient Conditions in the Investigation and Manufacturing of Drug Forms.

For the formation of a drug, a pharmacologically active compound must be prepared in a specific form. The drug must be manufactured, packaged, stored, transported, administred and delivered to a target in the body. To successfully prepare a drug form that will be robust through manufacturing, stable before administration and active with high bioavailability after administration, one needs to produce solid forms with controlled crystal structure and particle size and shape - often as multi-component composites. Considering drugs as materials, one can apply the knowledge of solid-state chemistry and materials science and non-ambient conditions to obtain solid forms with optimized properties. These conditions include, among others, different types of mechanical and ultrasonic treatment, hydrostatic compression, high-temperature or cryogenic spray-drying and crystallization from supercritical solvents. Solid-state reactions (e.g. dehydration or clathrate decomposition) can be effective in accessing metastable polymorphs or in micronizing a sample uniformly. To achieve control over the drug forms and the processes used for their robust manufacturing, one needs to take into account both the thermodynamic and kinetic aspects of their transformations.