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Mechanistic model for drug release during the lag phase from pellets coated with a semi-permeable membrane.

Marucci, Mariagrazia LU ; Ragnarsson, Gert; Nyman, Ulf LU and Axelsson, Anders LU (2008) In Journal of Controlled Release 127. p.31-40
Abstract
A new mechanistic model of drug release during the lag phase from coated pellets undergoing cracking in the coating due to the hydrostatic pressure built up inside the pellet has been developed. The model describes dynamically all the main release processes occurring during the lag phase in pellets coated with a semi-permeable membrane, i.e. the influx of solvent driven by the difference in osmotic pressure across the coating, dissolution of the drug, swelling of the pellet due to solvent accumulation, build-up of hydrostatic pressure inside the pellet, tensile stress acting on the coating, and the efflux of the dissolved drug. The water uptake is described using irreversible thermodynamics theory, while the tensile stress is described... (More)
A new mechanistic model of drug release during the lag phase from coated pellets undergoing cracking in the coating due to the hydrostatic pressure built up inside the pellet has been developed. The model describes dynamically all the main release processes occurring during the lag phase in pellets coated with a semi-permeable membrane, i.e. the influx of solvent driven by the difference in osmotic pressure across the coating, dissolution of the drug, swelling of the pellet due to solvent accumulation, build-up of hydrostatic pressure inside the pellet, tensile stress acting on the coating, and the efflux of the dissolved drug. The water uptake is described using irreversible thermodynamics theory, while the tensile stress is described using solid mechanics theory. Importantly, the model allows the prediction of the lag time prior to crack formation. The effect of the pellet size, the pellet shape and the coating thickness on the lag time and on the lag phase release profile has been investigated via computer simulations. The model was validated by comparison with dose release data obtained from pellets coated with an ethyl-cellulose-based film. The good agreement found between the predicted release and the experimental data confirmed the validity of the model. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Controlled Release
volume
127
pages
31 - 40
publisher
Elsevier
external identifiers
  • pmid:18262303
  • wos:000255296200004
  • scopus:40649088816
ISSN
1873-4995
DOI
10.1016/j.jconrel.2007.12.003
language
English
LU publication?
yes
id
51b50276-cdcb-47ed-b08c-1d87d98e3bfd (old id 1042112)
date added to LUP
2008-03-13 13:33:09
date last changed
2017-01-01 04:35:29
@article{51b50276-cdcb-47ed-b08c-1d87d98e3bfd,
  abstract     = {A new mechanistic model of drug release during the lag phase from coated pellets undergoing cracking in the coating due to the hydrostatic pressure built up inside the pellet has been developed. The model describes dynamically all the main release processes occurring during the lag phase in pellets coated with a semi-permeable membrane, i.e. the influx of solvent driven by the difference in osmotic pressure across the coating, dissolution of the drug, swelling of the pellet due to solvent accumulation, build-up of hydrostatic pressure inside the pellet, tensile stress acting on the coating, and the efflux of the dissolved drug. The water uptake is described using irreversible thermodynamics theory, while the tensile stress is described using solid mechanics theory. Importantly, the model allows the prediction of the lag time prior to crack formation. The effect of the pellet size, the pellet shape and the coating thickness on the lag time and on the lag phase release profile has been investigated via computer simulations. The model was validated by comparison with dose release data obtained from pellets coated with an ethyl-cellulose-based film. The good agreement found between the predicted release and the experimental data confirmed the validity of the model.},
  author       = {Marucci, Mariagrazia and Ragnarsson, Gert and Nyman, Ulf and Axelsson, Anders},
  issn         = {1873-4995},
  language     = {eng},
  pages        = {31--40},
  publisher    = {Elsevier},
  series       = {Journal of Controlled Release},
  title        = {Mechanistic model for drug release during the lag phase from pellets coated with a semi-permeable membrane.},
  url          = {http://dx.doi.org/10.1016/j.jconrel.2007.12.003},
  volume       = {127},
  year         = {2008},
}