Polymorphism

Synchrotron

For the last 5 years, Improved Pharma has carried out a number of Synchrotron-based studies at Argonne National Laboratory, and especially beamlines 6-ID-D and 11-BM.  Beamline 11-BM is optimized for powder diffraction analysis of crystals and formulations containing crystalline materials and beamline 6-ID-D is optimized for total scattering analysis of amorphous materials and formulations.  Both of these beamlines are the best in the world or among the best two or three beamlines in the world for their particular analysis.  Improved Pharma has the required arrangements with the US Department of Energy to use these facilities for proprietary measurements.  Additionally, Improved Pharma has the proper agreements to carry out proprietary studies at the Industrial Pharmacy Services Laboratory and at charge-back X-ray diffraction, NMR, and porcine pharmacology centers at Purdue University.  The COO of Improved Pharma is responsible for all studies and has access to consultants and technicians needed to carry out all of the studies in a highly accurate, professional manner.

·       Structure of amorphous formulations at the angstrom level using PDF

Pair distribution function (PDF) analysis of amorphous materials is a well-established technique having been used for many years in the physics and materials science community.  Our research team at Purdue began using this method in the early 2000s for analysis of the structure of pharmaceutical liquid crystals.  Then in the last few years, our team has used this method for amorphous pharmaceutical materials and pharmaceutical formulations.  Recently, our team published a major paper in Nature Scientific Reports (de Araujo, G. L. B., Benmore, C.J., Byrn, S.R., Local Structure of Ion Pair Interaction in Lapatinib Amorphous Dispersions characterized by Synchrotron X-Ray diffraction and Pair Distribution Function Analysis. Nature Sci. Rep. 7, 46367; doi: 10.1038/srep46367 (2017).  This paper showed that for lapatinib (a weak base containing a secondary amine) only an amorphous dispersion with the salt forming polymer HPMCP gave a dispersion devoid of the lapatinib-lapatinib interactions present in the pure amorphous drug and in HPMC dispersions.  Furthermore, stability studies showed that pure lapatinib and the HPMC dispersions crystallized but the amorphous dispersion devoid of molecule-molecule interactions was stable to crystallization.  This study also showed that pair distribution function analysis can determine the structure of amorphous dispersions and formulations down to the angstrom level.  Heretofore, the highest resolution technique was solid-state NMR relaxation times which was able to determine domain sizes an order of magnitude larger (10 to 300-angstrom level).

Improved Pharma provides services that can determine the structure of your dispersion using this same method.  Our approach allows selection of the most stable formulation without long-term stability studies.  Improved Pharma can also carry out solid-state NMR studies or other analytical testing on dispersions if requested.

·       Structure of nanoparticles using PDF

Professor Billinge has utilized PDF to detect nanoparticles of drugs in suspension.  This capability is helpful for understanding the behavior of nanoparticulate formulations. 

·       Amorphous Screening using Levitated Drops

Our team has also collaborated over the past few years with Dr. Rick Weber, CEO, of Materials Development, Inc., Evanston, IL and Dr. Chris Benmore of Argonne National lab to levitate drops of organic solvents containing various ratios of drug and polymer.  As these drops evaporate, the total X-ray scattering is measured and converted into PDF patterns for analysis.  This analysis allows for the rapid determination of the optimum polymer and polymer ratio for scale-up and testing.  Thus, Improved Pharma can perform amorphous formulation screens in a rapid and efficient manner.  In some cases, standard fast evaporation techniques are also used for Improved Pharma’s amorphous screens.

·       Structural Studies and Phase Diagrams of Liquid Crystals, Cocrystals, and other Complex Systems

Improved Pharma can also carry out structural studies of liquid crystals, cocrystals, and other complex systems.  Further, Improved Pharma can construct phase diagrams of complex systems to further understand the structure and properties of these systems.

·       Structure Determination using Powder Diffraction

Through its collaboration with Excelsus, Improved Pharma can determine the structure of materials using X-ray powder diffraction.  Having the crystal structure available provides invaluable insight into its material properties. 

 

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Powerful methods of analysis including IVIVC

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Quality by Design for formulations

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Rapid assessment of the risk of stability problems

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