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Screening and Characterization of Hydrate Forms of T-3256336, a Novel Inhibitor of Apoptosis (IAP) Protein Antagonist.
Chem Pharm Bull (Tokyo). 2015; 63(11):858-65.CP

Abstract

Different crystal packing of hydrates from anhydrate crystals leads to different physical properties, such as solubility and stability. Investigation of the potential of varied hydrate formation, and understanding the stability in an anhydrous/hydrate system, are crucial to prevent an undesired transition during the manufacturing process and storage. Only one anhydrous form of T-3256336, a novel inhibitor of apoptosis (IAP) protein antagonist, was discovered during synthesis, and no hydrate form has been identified. In this study, we conducted hydrate screening such as dynamic water vapor sorption/desorption (DVS), and the slurry experiment, and characterized the solid-state properties of anhydrous/hydrate forms to determine the most desirable crystalline form for development. New hydrate forms, both mono-hydrate and hemi-hydrate forms, were discovered as a result of this hydrate screening. The characterization of two new hydrate forms was conducted, and the anhydrous form was determined to be the most desirable development form of T-3256336 in terms of solid-state stability. In addition, the stability of the anhydrous form was investigated using the water content and temperature controlled slurry experiment to obtain the desirable crystal form in the crystallization process. The water content regions of the stable phase of the desired form, the anhydrous form, were identified for the cooling crystallization process.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Takeuchi S
Analytical Development Laboratories, CMC Center, Takeda Pharmaceutical Company Limited.
Kojima T
No affiliation info available
Hashimoto K
No affiliation info available
Saito B
No affiliation info available
Sumi H
No affiliation info available
Ishikawa T
No affiliation info available
Ikeda Y
No affiliation info available

MeSH

Calorimetry, Differential ScanningCrystallography, X-RayDrug DiscoveryDrug StabilityHumansHumidityInhibitor of Apoptosis ProteinsModels, MolecularOligopeptidesPhase TransitionPyrazinesSolubilityWater

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26521850

Citation

Takeuchi, Shoko, et al. "Screening and Characterization of Hydrate Forms of T-3256336, a Novel Inhibitor of Apoptosis (IAP) Protein Antagonist." Chemical & Pharmaceutical Bulletin, vol. 63, no. 11, 2015, pp. 858-65.
Takeuchi S, Kojima T, Hashimoto K, et al. Screening and Characterization of Hydrate Forms of T-3256336, a Novel Inhibitor of Apoptosis (IAP) Protein Antagonist. Chem Pharm Bull (Tokyo). 2015;63(11):858-65.
Takeuchi, S., Kojima, T., Hashimoto, K., Saito, B., Sumi, H., Ishikawa, T., & Ikeda, Y. (2015). Screening and Characterization of Hydrate Forms of T-3256336, a Novel Inhibitor of Apoptosis (IAP) Protein Antagonist. Chemical & Pharmaceutical Bulletin, 63(11), 858-65. https://doi.org/10.1248/cpb.c15-00262
Takeuchi S, et al. Screening and Characterization of Hydrate Forms of T-3256336, a Novel Inhibitor of Apoptosis (IAP) Protein Antagonist. Chem Pharm Bull (Tokyo). 2015;63(11):858-65. PubMed PMID: 26521850.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Screening and Characterization of Hydrate Forms of T-3256336, a Novel Inhibitor of Apoptosis (IAP) Protein Antagonist. AU - Takeuchi,Shoko, AU - Kojima,Takashi, AU - Hashimoto,Kentaro, AU - Saito,Bunnai, AU - Sumi,Hiroyuki, AU - Ishikawa,Tomoyasu, AU - Ikeda,Yukihiro, PY - 2015/11/3/entrez PY - 2015/11/3/pubmed PY - 2016/5/18/medline SP - 858 EP - 65 JF - Chemical & pharmaceutical bulletin JO - Chem Pharm Bull (Tokyo) VL - 63 IS - 11 N2 - Different crystal packing of hydrates from anhydrate crystals leads to different physical properties, such as solubility and stability. Investigation of the potential of varied hydrate formation, and understanding the stability in an anhydrous/hydrate system, are crucial to prevent an undesired transition during the manufacturing process and storage. Only one anhydrous form of T-3256336, a novel inhibitor of apoptosis (IAP) protein antagonist, was discovered during synthesis, and no hydrate form has been identified. In this study, we conducted hydrate screening such as dynamic water vapor sorption/desorption (DVS), and the slurry experiment, and characterized the solid-state properties of anhydrous/hydrate forms to determine the most desirable crystalline form for development. New hydrate forms, both mono-hydrate and hemi-hydrate forms, were discovered as a result of this hydrate screening. The characterization of two new hydrate forms was conducted, and the anhydrous form was determined to be the most desirable development form of T-3256336 in terms of solid-state stability. In addition, the stability of the anhydrous form was investigated using the water content and temperature controlled slurry experiment to obtain the desirable crystal form in the crystallization process. The water content regions of the stable phase of the desired form, the anhydrous form, were identified for the cooling crystallization process. SN - 1347-5223 UR - https://www.unboundmedicine.com/medline/citation/26521850/Screening_and_Characterization_of_Hydrate_Forms_of_T_3256336_a_Novel_Inhibitor_of_Apoptosis__IAP__Protein_Antagonist_ DB - PRIME DP - Unbound Medicine ER -