Progettazione, sintesi e caratterizzazione in solido di forme cristalline di farmaci, pesticidi e fitofarmaci, in accordo con i principi di green chemistry

Nanna, Saverio (2015) Progettazione, sintesi e caratterizzazione in solido di forme cristalline di farmaci, pesticidi e fitofarmaci, in accordo con i principi di green chemistry, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Chimica, 27 Ciclo. DOI 10.6092/unibo/amsdottorato/7050.
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This doctorate was funded by the Regione Emilia Romagna, within a Spinner PhD project coordinated by the University of Parma, and involving the universities of Bologna, Ferrara and Modena. The aim of the project was: - Production of polymorphs, solvates, hydrates and co-crystals of active pharmaceutical ingredients (APIs) and agrochemicals with green chemistry methods; - Optimization of molecular and crystalline forms of APIs and pesticides in relation to activity, bioavailability and patentability. In the last decades, a growing interest in the solid-state properties of drugs in addition to their solution chemistry has blossomed. The achievement of the desired and/or the more stable polymorph during the production process can be a challenge for the industry. The study of crystalline forms could be a valuable step to produce new polymorphs and/or co-crystals with better physical-chemical properties such as solubility, permeability, thermal stability, habit, bulk density, compressibility, friability, hygroscopicity and dissolution rate in order to have potential industrial applications. Selected APIs (active pharmaceutical ingredients) were studied and their relationship between crystal structure and properties investigated, both in the solid state and in solution. Polymorph screening and synthesis of solvates and molecular/ionic co-crystals were performed according to green chemistry principles. Part of this project was developed in collaboration with chemical/pharmaceutical companies such as BASF (Germany) and UCB (Belgium). We focused on on the optimization of conditions and parameters of crystallization processes (additives, concentration, temperature), and on the synthesis and characterization of ionic co-crystals. Moreover, during a four-months research period in the laboratories of Professor Nair Rodriguez-Hormedo (University of Michigan), the stability in aqueous solution at the equilibrium of ionic co-crystals (ICCs) of the API piracetam was investigated, to understand the relationship between their solid-state and solution properties, in view of future design of new crystalline drugs with predefined solid and solution properties.

Tipologia del documento
Tesi di dottorato
Nanna, Saverio
Dottorato di ricerca
Scuola di dottorato
Scienze chimiche
Settore disciplinare
Settore concorsuale
Parole chiave
solid-state, polymorphism, crystal engineering, solubility, folic acid, bentazon, imazamox, piracetam, solid state synthesis, mechanochemistry, co-crystal, ionic co-crystal, intrinsic dissolution rate, single crystal X-ray diffraction, X-ray powder diffraction, DSC, TGA, solid-state properties
Data di discussione
29 Aprile 2015

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