Protecting the crystalline integrity of your molecule, from milling to final shelf life.
Conditioning is a critical post-processing service designed to ensure the long-term physical stability and integrity of micronized pharmaceutical products. The two most common drawbacks of the micronization process, particularly when the jet mill is operated at high specific energy, are surface amorphization and product dehydration. Dehydration is a significant risk when nitrogen is used as the grinding gas, as the inert environment can trigger a transition of the API into an anhydrous form. In both scenarios, a post-micronization conditioning step is essential to stabilize the physical characteristics of the Drug Substance.
High specific energy frequently leaves particles in a high-energy, metastable state characterized by crystalline defects or surface amorphization. Because micronized materials have an exponentially increased surface area, they become significantly more hygroscopic, making them susceptible to moisture uptake. If left unmanaged, these amorphous surfaces can rapidly revert to a crystalline phase under ambient conditions, leading to unwanted particle aggregation, agglomeration and a subsequent increase in particle size.
Our conditioning services utilize controlled environmental chambers to manage the relaxation mechanism of the powder. By precisely controlling relative humidity and temperature, we allow amorphous content to stabilize or recrystallize in a controlled manner while facilitating the re-hydration of APIs that have transitioned into anhydrous forms. This ensures the API returns to its required hydrated crystalline state, preventing the formation of large lumps that could compromise downstream processing or the clinical efficiency of inhalation powders.
The efficacy of the conditioning process is monitored through rigorous solid-state characterization. We utilize Dynamic Vapor Sorption (DVS) to determine the amorphous content and susceptibility to moisture, alongside DSC and XRPD to confirm the stability of the crystalline polymorph. Implementing these stability-focused conditioning steps, guarantees that the API maintains its target PSD and biopharmaceutical exposure levels throughout its shelf life, ensuring consistent performance in clinical and commercial applications.
To prevent issues before they arise, we can integrate moisture control directly into the milling process by using humidified nitrogen as the grinding gas. This technique is particularly effective for reducing product dehydration during comminution or for facilitating the simultaneous re-crystallization of amorphous content as it is generated by the high-energy impacts.
In this protocol, the micronized product is spread uniformly on trays and placed within environmental chambers. The material is exposed to predetermined Relative Humidity (RH) and Temperature (T) conditions, allowing for the controlled relaxation of surface energy and the stabilization of the crystalline lattice.
For more intensive processing, the product is handled inside an ad hoc cyclone filter that functions as a fluid bed. Humidified nitrogen is insufflated into the system to keep the product in suspension, ensuring that every particle is uniformly exposed to the required moisture levels for rapid stabilization or re-hydration.
To prevent issues before they arise, we can integrate moisture control directly into the milling process by using humidified nitrogen as the grinding gas. This technique is particularly effective for reducing product dehydration during comminution or for facilitating the simultaneous re-crystallization of amorphous content as it is generated by the high-energy impacts.
In this protocol, the micronized product is spread uniformly on trays and placed within environmental chambers. The material is exposed to predetermined Relative Humidity (RH) and Temperature (T) conditions, allowing for the controlled relaxation of surface energy and the stabilization of the crystalline lattice.
For more intensive processing, the product is handled inside an ad hoc cyclone filter that functions as a fluid bed. Humidified nitrogen is insufflated into the system to keep the product in suspension, ensuring that every particle is uniformly exposed to the required moisture levels for rapid stabilization or re-hydration.
Conditioning is a "healing" step for medicine powders after they have been shrunk into tiny pieces. High-speed crushing can sometimes damage the surface of the particles or dry them out too much. These damaged particles act like sponges, soaking up moisture from the air and clumping together into large, messy lumps. During conditioning, we place the powder in special rooms with carefully controlled temperature and moisture. This allows the particles to "relax" and return to a stable, healthy state. This ensures the medicine stays effective and safe throughout its shelf life.
Whether you are at the start of your development journey or scaling to commercial supply, we are ready to work with you. Let's talk about your molecule.