Nearly half of newly discovered active pharmaceutical ingredients (APIs) suffer from poor dissolution in water. After finding a successful “hit” using high throughput screening methodologies, many promising APIs must undergo subsequent chemical modification to improve the dissolution behavior. Pharmaceutical cocrystals are of growing interest as a means of controlling the release of an active pharmaceutical ingredient (API) without modifying its molecular structure.
Pharmaceutical cocrystals are typically defined as a combination of two organic compounds in solid form, held together by hydrogen bonds and van der Waals forces and simple stoichiometries (e.g., 1:1, 1:2, etc. molar ratios) of API and coformer. By choosing an appropriate coformer, the dissolution behavior of the API (i.e. its concentration over time) can be controlled and even enhanced significantly over the pure form and can have many functional advantages. Current methods of creating pharmaceutical cocrystals, however, are limited by the necessity for a liquid solvent during synthesis, required post-processing, and compatible delivery methods.
We have developed a novel, solvent-free method for synthesizing organic cocrystals. The method, organic vapor cocrystalization (OVCC), involves subliming the API and co-former into a carrier gas, followed by jetting the gas mixture onto a temperature-controlled substrate, where the organic materials condense to form the cocrystal film. As proof of concept, we demonstrate for the first time the synthesis of the cocrystal system of caffeine and succinic acid, whose isolation has not been previously obtained by conventional methods. X-ray diffraction and differential scanning calorimetry are used to confirm the presence of the cocrystal phase, while scanning electron microscopy studies show that the cocrystal forms an elongated morphology comprised of long needles, whose length and orientation depend on process parameters.
Because a liquid solvent is not needed, OVCC opens the door to new cocrystal systems and printing applications. The new OVCC process enables excellent process control and automation, andautomation and is highly scalable for the manufacturing of cocrystal products.