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Preparation and characterization of functional particles for inhalation

Marcin Odziomek

Abstract

The thesis is focused on the application of chemical and process engineering methodology to develop inhalable particles with functionality which allows them to modify of bronchial mucus. The functional particles were produced by spray drying in controlled conditions using appropriately selected aqueous precursors containing excipients currently approved for pharmaceutical use or waiting for the approval. The mucolytic – N-acetylcystine (NAC) was used as the excipient modifying the mucus structure. In order to ensure required stability of functional particles and their good aerosol properties it was necessary to use additional substances: low molecular weight dextran (4 kDa) and mannitol. Based on these excipients two types of particles were produced: a) two-component particles which can be used as carriers for different drug particles; b) three-component particles which contain the drug in its structure. Powders were characterized in respect of the most important physicochemical properties including: size, water content, glass transition temperature – Tg and morphology. The important therapeutic indicators such like fine particle fraction (FPF) and mass median aerodynamic diameter (MMAD) were determined for aerosols obtained after dispersion of the powders. Additionally, the efficiency of spray-drying process was determined. The results of experimental studies have been supplemented by results of mathematical modelling which described the process of evaporation of multicomponent droplet and particle forming. The results obtained in this part indicate that spray drying technique allows to produce inhalation powders which are characterized by the required aerodynamic parameters and which contain the functional ingredient (NAC). Based on the experimental results it was proven that production process performance and effective resuspension of obtained powders is correlated to the glass transition temperature. The high value of Tg was ensured by using dextran as additional compound. Powders obtained from this excipient and NAC were characterized by very good aerosol parameters, which - as shown by mathematical modeling - can also be the result of favorable components segregation inside the produced particles.
Record ID
WUT4dc9d13272b84ca19d05e8b1ce33d50d
Diploma type
Doctor of Philosophy
Author
Title in Polish
Otrzymywanie i badanie właściwości funkcjonalnych cząstek inhalacyjnych
Title in English
Preparation and characterization of functional particles for inhalation
Language
(pl) Polish
Certifying Unit
Faculty of Chemical and Process Engineering (FCPE)
Discipline
chemical engineering / (technology domain) / (technological sciences)
Status
Finished
Start date
26-06-2012
Defense Date
28-10-2014
Supervisor
External reviewers
Andrzej Noworyta Andrzej Noworyta,, External affiliation of publication: Zakład Procesów Chemicznych i Biochemicznych
Marek Darowski Marek Darowski,, External affiliation of publication: Instytut Biocybernetyki i Inżynierii Biomedycznej im. Macieja Nałęcza Polskiej Akademii Nauk
Honored
yes
Pages
155
Internal identifier
DICHP-2335
Keywords in English
xxx
Abstract in English
The thesis is focused on the application of chemical and process engineering methodology to develop inhalable particles with functionality which allows them to modify of bronchial mucus. The functional particles were produced by spray drying in controlled conditions using appropriately selected aqueous precursors containing excipients currently approved for pharmaceutical use or waiting for the approval. The mucolytic – N-acetylcystine (NAC) was used as the excipient modifying the mucus structure. In order to ensure required stability of functional particles and their good aerosol properties it was necessary to use additional substances: low molecular weight dextran (4 kDa) and mannitol. Based on these excipients two types of particles were produced: a) two-component particles which can be used as carriers for different drug particles; b) three-component particles which contain the drug in its structure. Powders were characterized in respect of the most important physicochemical properties including: size, water content, glass transition temperature – Tg and morphology. The important therapeutic indicators such like fine particle fraction (FPF) and mass median aerodynamic diameter (MMAD) were determined for aerosols obtained after dispersion of the powders. Additionally, the efficiency of spray-drying process was determined. The results of experimental studies have been supplemented by results of mathematical modelling which described the process of evaporation of multicomponent droplet and particle forming. The results obtained in this part indicate that spray drying technique allows to produce inhalation powders which are characterized by the required aerodynamic parameters and which contain the functional ingredient (NAC). Based on the experimental results it was proven that production process performance and effective resuspension of obtained powders is correlated to the glass transition temperature. The high value of Tg was ensured by using dextran as additional compound. Powders obtained from this excipient and NAC were characterized by very good aerosol parameters, which - as shown by mathematical modeling - can also be the result of favorable components segregation inside the produced particles.
Thesis file
  • File: 1
    Odziomek.pdf
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Reviews
  • File: 1
    M. Odziomek - Recenzja 1.pdf
  • File: 2
    M. Odziomek - Recenzja 2.pdf
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Uniform Resource Identifier
https://repo.pw.edu.pl/info/phd/WUT4dc9d13272b84ca19d05e8b1ce33d50d/
URN
urn:pw-repo:WUT4dc9d13272b84ca19d05e8b1ce33d50d

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