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Spray Drying of Cocrystals for Engineering Particle Properties: Diploma Work
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
2015 (English)Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

The goals of this work were to combine crystal and particle engineering in a single

step using spray drying and improve particle properties that can potentially minimize

the need for coating agents. Specific aim was to prepare and characterize theophylline

cocrystal particles intended for inhalation using by spray drying.

Theophylline is a bronchodilator used in the treatment of asthma and is used as a

model drug in this study. Theophylline cocrystals with citric acid, flufenamic acid and

saccharin were chosen as model systems. The solubilities of different components of

cocrystals in different solvents were determined to get an idea of the stability

landscape of cocrystals. Thereafter, the cocrystals were prepared by slurry

crystallization method. The cocrystal particles from similar solutions were prepared

using spray drying. The processing variables are carefully chosen for optimal particle

engineering. The resulting solids were subjected to different characterizations such as

particle size analysis, tap density and bulk density analysis and new generation

impactor studies.

Theophylline cocrystals were successfully obtained by both slurry crystallization and

spray drying methods. Despite rapid drying, spray dried particles were predominantly

crystalline with a particle size and other attributes suitable for inhalation. However,

the process yields were low due to adhesion to cyclone walls. The impactor results

indicated a decent aerosolization performance of the spray dried particles in pure and

when blended with lactose.

The cocrystal particles with interesting properties suitable for inhalation application

can be prepared in one step using spray drying. The mechanisms behind reasons for

adhesion of cocrystal particles should be further elucidated.

Key words: spray drying, cocrystals, cocrystallization, coformers, particle engineering,

design of experiments, inhalation, theophylline, citric acid, flufenamic acid, saccharin.

Place, publisher, year, edition, pages
UPTEC K, ISSN 1650-8297 ; 15029
National Category
Chemical Sciences
URN: urn:nbn:se:uu:diva-265788OAI: diva2:866593
External cooperation
AstraZeneca, Mölndal
Educational program
Master Programme in Chemical Engineering
Available from: 2016-01-07 Created: 2015-11-03 Last updated: 2016-01-07Bibliographically approved

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