Ghazala Sadiq, Shubham Sharma, Joanna S Stevens, Pablo Martinez-Bulit, Lily M Hunnisett, Christopher Cameron, Brian Samas, Emma Hawking, Nicholas Francia, Jeff Lengyel, Elna Pidcock, Sadia Rahman, Matthew Nisbet, Kevin Back, Cheryl Doherty, Patricia Basford, Timothy G Cooper, Garry O'Connor, Rajni M Bhardwaj
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An integrated approach combining experimental, informatics and energetic methods for solid form derisking of PF-06282999.
The landscapes of observed and predicted three-dimensional crystal packing arrangements of small-molecule drug candidates can be complex. The possible appearance of a more thermodynamically stable solid form during drug development has led to the digital workflow of informatics-based risk assessments, named a Solid Form Health Check. Herein, we describe the use of a combined approach consisting of experiments, informatics together with energetic calculations in analysis of four competing polymorphs of PF-06282999, a myeloperoxidase (MPO) inhibitor with conformational flexibility and multiple plausible hydrogen bond networks. This combined approach offered a comprehensive understanding of the solid form structure, properties, and performance, ensuring robust solid form derisking and selection.
期刊介绍:
The Journal of Pharmaceutical Sciences will publish original research papers, original research notes, invited topical reviews (including Minireviews), and editorial commentary and news. The area of focus shall be concepts in basic pharmaceutical science and such topics as chemical processing of pharmaceuticals, including crystallization, lyophilization, chemical stability of drugs, pharmacokinetics, biopharmaceutics, pharmacodynamics, pro-drug developments, metabolic disposition of bioactive agents, dosage form design, protein-peptide chemistry and biotechnology specifically as these relate to pharmaceutical technology, and targeted drug delivery.