Application of Low-Frequency (LF) Raman Spectroscopy to an Isoenergetic Polymorph Study

This application note outlines the evaluation of post-dissolution ACE SDD. The results indicated that in all of the cases studied, ACE remained amorphous upon dissolution if it was intimately mixed in the dispersion. However, phase separation from the polymer allowed ACE to crystallize as expected. Interestingly, the type of polymer used affected the ACE polymorph generated. The mixture of polymorphs was observed in the powder X-ray diffraction (PXRD) result (though it could easily be overlooked), while LF Raman maps showed distinct regions of the different polymorphs. This study demonstrated the utility of LF Raman mapping in elucidating the dissolution mechanism of amorphous dispersions. Keywords: Low Frequency Raman, Amorphous, Spray dried dispersion, Dissolution, Crystallization, Polymorphs

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What is the impact of recent changes in FDA guidance on regulatory and intellectual property issues? The FDA reclassification of cocrystals as active pharmaceutical ingredients (APIs) has created exciting opportunities for the pharmaceutical industry. That reclassification means cocrystals can now be developed as if they were polymorphs, providing new avenues for dealing with poor API physical properties and extending intellectual property lifetimes. It is important to understand how the revised guideline impacts API development, regulatory submissions, and intellectual property protection. Those topics are discussed in this whitepaper. Also considered is the importance of identifying whether an API is a salt or a cocrystal, a critical classification from a regulatory point of view. In addition, a list of FDA-approved, marketed cocrystals is presented. Finally, recommendations for cocrystal screening, evaluation, formulation, and production at scale are given.

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Amorphous solid dispersions (ASD) have long been used to increase the solubility and bio-availability of poorly-soluble compounds. A considerable amount of research has been car-ried out and has generated useful techniques in the area of ASD development. Surprisingly, the number of examples with successful application of the available techniques has been meager. Herein, a case study with nifedipine is presented where ASD candidates were rap-idly determined within 2-3 weeks by utilizing a compilation of these techniques. Keywords: Amorphous Solid Dispersion (ASD), Spray Drying, Crystallization, Solubility, Sta-bility, Dissolution

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