Characterization of the Mechanisms of Drug Release from Polymer-Coated Formulations using Experiments and Modelling

Mariagrazia Marucci

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

Sammanfattning

The main objectives of the work presented in this thesis were to develop new experimental methods to improve the understanding of the release mechanism from a coated formulation and to develop new mechanistic models to describe the release process for pellets coated with a semi-permeable film. Another aim was to characterize the release mechanism from a formulation coated with films made of a blend of a water-insoluble polymer, ethyl cellulose (EC), and a water-soluble polymer, hydroxypropyl cellulose (HPC). The work dealt with free films intended for coating and with coated multiple-unit systems.
Two methodologies were mainly used in the study of free films. Electronic speckle pattern interferometry made it possible to discriminate between a semi-permeable and a permeable film. For a permeable film, the effective diffusion coefficient of a drug in the film was determined. A new release cell equipped with a manometer was developed. The combination of pressure and release data made it possible to easily and accurately characterize the release mechanism, to discriminate between semi-permeable and permeable films, and to detect changes in the structure of the film and in the release mechanism during the release.
A mechanistic model describing the lag phase of pellets coated with a semi-permeable film undergoing cracking due to hydrostatic pressure build-up was developed. The model was validated against experimentally determined whole-dose release profiles of pellets coated with an EC-based film. The model showed that a small variation in the film thickness has a significant influence on the lag time. A mechanistic model to describe the osmotic pumping release from pellets coated with a semi-permeable film containing water-filled channels was also developed. The model was validated by comparison with experimentally determined release profiles of single pellets coated with a film made of EC and HPC. Via model simulation it was found that the concentration profile in the channels was almost constant.
The HPC content of EC/HPC films affects the amount of HPC leached out of the films, and thus the release mechanism. The release mechanism changed from osmotic pumping to diffusion as the amount of HPC increased. When release occurs by diffusion, the effective diffusion coefficient of a drug in the coating is not constant but increases significantly during the release process as a consequence of HPC leaching.
Originalspråkengelska
KvalifikationDoktor
Tilldelande institution
  • Institutionen för kemiteknik
Handledare
  • Axelsson, Anders, handledare
Tilldelningsdatum2009 apr. 3
Förlag
StatusPublished - 2009

Bibliografisk information

Defence details

Date: 2009-04-03
Time: 13:15
Place: Lecture hall K:C, Center for Chemistry and Chemical Engineering, Getingevägen 60, Lund University Faculty of Engineering

External reviewer(s)

Name: Grassi, Mario
Title: [unknown]
Affiliation: Faculty of Engineering, University of Trieste, Italien

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Ämnesklassifikation (UKÄ)

  • Kemiteknik

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