Active Pharmaceutical Ingredient (API) is the biologically active component of a drug product (tablet, capsule, cream, injectable) that produces the intended effects. APIs including biological API and intermediate API find application in high quality drugs that treat diseases pertaining to oncology, cardiology, CNS and neurology, orthopaedic, pulmonology, gastroenterology, nephrology, ophthalmology, and endocrinology. APIs can potentially create a more sustainable healthcare system by introducing more innovative products.






How APIs are made


API and raw material are often confused due to the similar usage of the two terms. What is the difference? Raw material refers to chemical compounds that are used as a base to make an API. The API is not made by only one reaction from the raw materials but rather it becomes an API via several chemical compounds. The chemical compound which is in the process of becoming an API from a raw material is called an intermediate. Among the APIs, there is an API which passes through over ten kinds of intermediates in a process when it changes from being a raw material into an API. After this long manufacturing process, it is purified until it reaches a very high degree of purity and finally becomes an API.






Strength of APIs


Manufacturers use certain standards to determine how strong the API is in each drug. However, the standard can vary widely from one brand and process to another. Each brand might use different test methods, that can result in different potencies.






In all cases, manufacturers are required by the FDA to prove the potency of their products in real-life patients, as well as in laboratory conditions.






The API form that is used in a formulation is often the most thermodynamically stable crystalline form. As such, the phenomenon of hydrogen bonding in combination with there being many functional groups on the API usually results in the available crystalline form being a hydrate.






Because of this fact the hydration behavior of crystalline APIs is of particularly high importance within the pharmaceutical industry, and is vastly studied from every possible angle. The state of hydration has a direct effect on the physical properties of the API, which in turn has a large impact on the drug processability and how the drug will eventually perform in-vivo, i.e. stability, solubility, and bioavailability.






Recently, a team of scientists in the department of Drug Product Science and Technology, at Bristol-Myers Squibb, USA have developed a supplementary technique to complement more conventional analysis (methods such as calorimetric studies, nuclear magnetic resonance and vibrational spectroscopy) to study the behavior of hydration in organic crystalline solids.






By performing single crystal X-ray diffraction experiments with the ultimate objective being interpretation of the non-Bragg diffraction features, Chan et al, Acta Cryst. (2014). B70, 555-567 were able to gain further insight into the mechanical and structural details of the dehydration of the crystal. These scattering features were reproduced and studied using computer models and the results were able to show the mechanistic relationships between changes in the lattice structure as stages of the overall drying process.






This study is the first of its kind to combine the mechanism of dehydration and non-Bragg scattering features from a single API crystal and the results will further improve the knowledge, formulation and choice of API used in drug manufacture today. The group at BMS anticipates that these same data interpretation techniques will be useful to other researchers and that a more user friendly modeling software can be made available in the future.