• Survey of methodologies of pharmaceutical interest for quantification of crystal form via X-Ray Powder Diffraction
  • Dall'Olio, Laura <1991>


  • CHIM/03 Chimica generale e inorganica


  • 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.


  • 2021-05-31


  • Doctoral Thesis
  • PeerReviewed


  • application/pdf



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.