Coupling Polymorphism/Solvatomorphism and Physical Stability Evaluation with Early Salt Synthesis Optimization of an Investigational Drug
| Autor: | Arto Tolvanen, Jouko Yliruusi, Saara Tiittanen, Karjalainen Arto Johannes, Mäkelä Mikko, David Din Belle, Veli Pekka Tanninen, Anna Shevchenko, Jorma Haarala, Inna Miroshnyk |
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| Rok vydání: | 2011 |
| Předmět: |
Investigational drug
010405 organic chemistry Chemistry Stereochemistry Hemihydrate Organic Chemistry Sorption 02 engineering and technology 021001 nanoscience & nanotechnology 01 natural sciences 0104 chemical sciences Chemical engineering Polymorphism (materials science) Anhydrous Gravimetric analysis Physical stability Physical and Theoretical Chemistry 0210 nano-technology Powder diffraction |
| Zdroj: | Organic Process Research & Development. 15:666-672 |
| ISSN: | 1520-586X 1083-6160 |
| Popis: | The need for effective solid-form screening approaches, especially designed for the early discovery phases, is well recognized within the pharmaceutical industry. Here we report on the early polymorphism and solvatomorphism evaluation of a new drug candidate for selective α2C-adrenoceptor antagonists ORM10921·HCl. The approach we use is based on the systematic batch-to-batch characterization of the solids generated during the salt synthesis optimization. Within this study three crystalline forms, two anhydrous and one hemihydrate, were discovered and identified by X-ray powder diffraction (XRPD), differential scanning calorimery (DSC), and thermal gravimetry (TGA). Moreover, coupling the gravimetric vapor sorption analysis with a conventional XRPD enabled the relative stability of these solid-state forms at ambient conditions to be established and the most stable form, the hemihydrate, to be selected for further development. Hence, the utilized approach has proven to be an effective and fast tool for init... |
| Databáze: | OpenAIRE |
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