Survey of methodologies of pharmaceutical interest for quantification of crystal form via X-Ray Powder Diffraction

Dall'Olio, Laura (2021) Survey of methodologies of pharmaceutical interest for quantification of crystal form via X-Ray Powder Diffraction, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Nanoscienze per la medicina e per l'ambiente, 33 Ciclo. DOI 10.48676/unibo/amsdottorato/9769.
Documenti full-text disponibili:
[img] Documento PDF (English) - Richiede un lettore di PDF come Xpdf o Adobe Acrobat Reader
Disponibile con Licenza: Salvo eventuali più ampie autorizzazioni dell'autore, la tesi può essere liberamente consultata e può essere effettuato il salvataggio e la stampa di una copia per fini strettamente personali di studio, di ricerca e di insegnamento, con espresso divieto di qualunque utilizzo direttamente o indirettamente commerciale. Ogni altro diritto sul materiale è riservato.
Download (22MB)

Abstract

The interest on polymorphism of arises from their different properties. A strategy to improve the properties of compound, is the formation of cocrystal. In this PhD project, cocrystal statistical analysis and experimental screening of allantoin and some coformers were performed. No cocrystal was obtained, experimental results disagree with the statistical analysis. Quantitative method of crystalline forms via X-Ray Powder Diffraction are extremely interesting for pharmaceutical companies. In the thesis real cases with different approaches of quantitative analysis are reported. I presented the quantification of paracetamol form II impurity in Tachifludec containing paracetamol form I using univariate method in which the main issue is the identification of a specific peak. The presence of several peaks in the formulation was overcome by applying the standard addition method spiking the formulation with form II. Univariate and multivariate method NAS were compared, and the best results were obtained with the application of the multivariate method. These approaches were also evaluated in the case of mixture amorphous-crystalline. Furthermore, it was studied the potential use of stable amorphous surrogate instead to the unstable real amorphous. Even in these cases, multivariate method achieved the best results. The novel quantification method Direct derivation (DD) based on intensity–composition equation was applied to determine crystallinity of mixture amorphous-crystalline. The quantification method was evaluated in three scenarios: method a) with unit cell parameters, method b) structural information is unknown, and method c) only the mixtures’ patterns are available. Method a and b achieved more accurate results because of better description of the crystalline phase. Method b was evaluated in sample covered by containment system as the Kapton® film to evaluate the analysis of highly potent compounds. The DD method has been revealed the best method to estimate the crystallinity degree of formulation containing highly potent compound deposited on catheter balloon.

Abstract
Tipologia del documento
Tesi di dottorato
Autore
Dall'Olio, Laura
Supervisore
Co-supervisore
Dottorato di ricerca
Ciclo
33
Coordinatore
Settore disciplinare
Settore concorsuale
Parole chiave
X-ray powder diffraction, quantification, cocrystal, allantoin, paracetamol, stardard addition method, crystalline, amorphous, drug coated balloon, direct-derivation method, solid-state, high potent compound, polymorphism, crystallinity degree
URN:NBN
DOI
10.48676/unibo/amsdottorato/9769
Data di discussione
31 Maggio 2021
URI

Altri metadati

Statistica sui download

Gestione del documento: Visualizza la tesi

^