As changes are made to the manufacturing process during drug development, it is often necessary to ensure that a drug or drug product made in a new way is the same as the material produced using the original methods. These equivalence studies often focus on chemical or physical properties and are relatively straight-forward for well-defined, crystalline materials. However, what about amorphous materials? Contrary to popular belief, there is structure in an amorphous material and this structure can be the cause of a batch of material passing or failing a stability test. To fully assess the structure, powerful synchrotron X-ray Pair Distribution Function (SXPDF) techniques are required. Improved Pharma, LLC has spent years honing the approach at Argonne National Laboratory, working alongside Dr. Chris Benmore, an expert in the field. This technology is now available as a protocol-based proprietary service for the Pharmaceutical industry.
Specifically, PDF methods can be used to:
- Determine the sameness of amorphous dispersions prepared by different techniques such as spray drying and hot melt extrusion. For amorphous dispersions, the PDF provides information on the miscibility of the system and the presence of domains of API molecules, which would lead to crystallization.
- Determine the sameness of API samples prepared under different milling, crystallization, or drying conditions. For API samples prepared in different ways, the PDF pattern reflects the degree of disorder in the material.
- Provide information on the structures of liquid crystals and nanoparticles. We have established a formal collaboration with Professor Simon Billinge, a recognized leader in the field of using synchrotron-based methods to analyze nanoparticles.
All these methods provide important regulatory information including the sameness of different trial formulations and clinical trial lots. Improved Pharma can also perform more conventional sameness studies including: (1) Determination of the sameness of the solid form present; (2) Design of sameness methods; (3) Determination of the form of the drug substance in the drug product; (4) Verification that the drug substance has not changed in the drug product; and (5) Accelerated stability studies to test sameness.
For a protocol aimed at solving sameness problems please contact Improved Pharma at email@example.com.