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Process-induced disorder of pharmaceutical materials : Mechanisms and quantification of disorder

One of the most important prerequisites in the drug development is to attain a reproducible and robust product in terms of its nature, and its chemical and physical properties. This can be challenging, since the crystalline form of drugs and excipients can be directly transformed into the amorphous one during normal pharmaceutical processing, referred to as process-induced amorphisation or process-induced disorder. The intention of this thesis was to address the mechanisms causing disorder during powder flow and milling and, in association with this, to evaluate, the ability of Raman spectroscopy and atomic force microscopy (AFM) to quantify and characterize process-induced disorder. The amorphisation mechanisms were controlled by stress energy distribution during processing, which in turn was regulated by a series of process parameters. Compression and shearing stress caused by sliding were stress types that acted on the particles during powder flow and ball milling process. However, sliding was the most important inter-particulate contact process giving rise to amorphisation and the transformation was proposed to be caused by vitrification. The plastic stiffness and elastic stiffness of the milling-induced particles were similar to a two-state particle model, however the moisture sorption characteristics of these particles were different. Thus the milled particles could not be described solely by a two-state particle model with amorphous and crystalline domains.  Raman spectroscopy proved to be an appropriate and effective technique in the quantification of the apparent amorphous content of milled lactose powder. The disordered content below 1% could be quantified with Raman spectroscopy. AFM was a useful approach to characterize disorder on the particle surfaces. In summary, this thesis has provided insight into the mechanisms involved in process-induced amorphisation of pharmaceutical powders and presented new approaches for quantification and characterization of disordered content by Raman spectroscopy and atomic force microscopy.

Identiferoai:union.ndltd.org:UPSALLA1/oai:DiVA.org:uu-317801
Date January 2017
CreatorsPazesh, Samaneh
PublisherUppsala universitet, Institutionen för farmaci, Uppsala
Source SetsDiVA Archive at Upsalla University
LanguageEnglish
Detected LanguageEnglish
TypeDoctoral thesis, comprehensive summary, info:eu-repo/semantics/doctoralThesis, text
Formatapplication/pdf
Rightsinfo:eu-repo/semantics/openAccess
RelationDigital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, 1651-6192 ; 228

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