Modelling of Drug Release from Reservoir and Matrix Formulations - Multiple Unit Dosage Forms and Swelling and Dissolving Matrix Systems
(2005)- Abstract
- In this work, mathematical models have been developed describing drug release from film-coated reservoir systems as well as drug release and polymer dissolution from swelling and dissolving polymer tablets. The model derivation of both systems is based on a mechanistic approach. The model describing drug release from reservoir systems, i.e. from single, film-coated pellets, was validated against experimental release data from single ethyl-cellulose-coated pellets. The model was also expanded to account for the simultaneous release from an ensemble of single pellets, i.e. a multiple-unit model. This study was verified against release data from ensembles of ethyl-cellulose-coated pellets. Qualitative studies using SEM on the film-coated... (More)
- In this work, mathematical models have been developed describing drug release from film-coated reservoir systems as well as drug release and polymer dissolution from swelling and dissolving polymer tablets. The model derivation of both systems is based on a mechanistic approach. The model describing drug release from reservoir systems, i.e. from single, film-coated pellets, was validated against experimental release data from single ethyl-cellulose-coated pellets. The model was also expanded to account for the simultaneous release from an ensemble of single pellets, i.e. a multiple-unit model. This study was verified against release data from ensembles of ethyl-cellulose-coated pellets. Qualitative studies using SEM on the film-coated pellets together with the information gained from the model evaluation of the experimental release data, indicated that a major release mechanism from these pellets is drug transport through cracks and holes in the polymer film. This finding confirms the view that it is essential to obtain information on release characteristics on the single-unit level in order to increase our knowledge concerning release-controlling mechanisms.The model for polymer swelling and dissolution, i.e. the polymer dissolution model, and the model for drug release from a swelling and dissolving polymer matrix, i.e. the drug release model, are based on mass transfer in cylindrical geometry. Diffusive and convective contributions to mass transfer are accounted for. The polymer dissolution model was fitted to experimental polymer dissolution and front position data of the dissolution of poly (ethylene oxide). The information gained from fitting was applied to the drug release model, which was validated against drug release data for a soluble drug and a slightly soluble drug. It was concluded that the convective contribution to drug mass transfer can be of considerable importance, leading to erroneous fitting results if neglected. (Less)
- Abstract (Swedish)
- Popular Abstract in Swedish
I denna avhandling behandlas modeller för simulering av läkemedelsfrisättning från enskilda filmdragerade pellets, samtidig frisättning från ett antal filmdragerade pellets, samt frisättning av läkemedel och/eller polymer från svällande polymertabletter. Modellerna är validerade mot experimentella data.
Modellen för frisättning från filmdragerade pellets är validerad mot experimentella frisättningsdata för enskilda pellets, samt data för frisättning från den slutliga läkemedelsdosen som består av ett större antal pellets. Vidare har kvalitativa studier utförts med hjälp av svepelektronmikroskopi och energidispersiv röntgenanalys på enskilda filmdragerade pellets. En slutsats... (More) - Popular Abstract in Swedish
I denna avhandling behandlas modeller för simulering av läkemedelsfrisättning från enskilda filmdragerade pellets, samtidig frisättning från ett antal filmdragerade pellets, samt frisättning av läkemedel och/eller polymer från svällande polymertabletter. Modellerna är validerade mot experimentella data.
Modellen för frisättning från filmdragerade pellets är validerad mot experimentella frisättningsdata för enskilda pellets, samt data för frisättning från den slutliga läkemedelsdosen som består av ett större antal pellets. Vidare har kvalitativa studier utförts med hjälp av svepelektronmikroskopi och energidispersiv röntgenanalys på enskilda filmdragerade pellets. En slutsats från arbetet är att frisättningen från den studerade formuleringen sker genom hål eller sprickor i polymerfilmen. Detta visar på hur viktigt det är att veta frisättningskarakteristika för enskilda pellets och inte bara för den slutliga läkemedelsdosen.
Modellerna för läkemedels och/eller polymerfrisättning från svällande polymertabletter är beskriver masstransporten av läkemedel och/eller lösningsmedel i en cylindrisk geometri. Diffusiva och konvektiva (svällning pga. diffusion) bidrag till masstransporten är inkluderat i modellbeskrivningen. Modellen för polymerfrisättning är validerad mot experimentella polymerupplösnings- och svällningsdata för polyetenoxid. Modellen för läkemedelsfrisättning från en svällande polymertablett är validerad mot experimentella frisättningsdata för en löslig och en obetydligt löslig aktiv substans. En slutsats av detta arbete är att det konvektiva bidraget till frisättningen kan vara av stor betydelse, beroende på den aktiva komponentens och polymerens fysikaliska egenskaper. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/544138
- author
- Borgquist, Per LU
- supervisor
- opponent
-
- Professor Siepmann, Juergen, College of Pharmacy Université de Lille 2 3, rue du Professor Laguesse, B.P. 83 59006 Lille Cedex, F
- organization
- publishing date
- 2005
- type
- Thesis
- publication status
- published
- subject
- keywords
- swelling, XEDS, Chemical technology and engineering, Kemiteknik och kemisk teknologi, Polymer technology, biopolymers, Polymerteknik, Pharmaceutical and related technologies, Läkemedelsteknik och relaterad teknik, simulation, single pellet, single-unit release, SEM, reservoir system, poly (ethylene oxide), film-coated, matrix, mathematical model, diffusion, pellet shape, controlled release, polymer dissolution, modelling, ethyl cellulose, Coating, multiple-unit release
- pages
- 222 pages
- publisher
- KFS AB
- defense location
- Kemicentrum, Getingevägen 60, Lund, hörsal A
- defense date
- 2005-02-04 10:30:00
- external identifiers
-
- other:ISRN: LUTKDH/(TKKA-1001)/1-109/(2005)
- ISBN
- 91-628-6374-6
- language
- English
- LU publication?
- yes
- id
- 896b983e-9a66-4745-a089-547cd44ab41c (old id 544138)
- date added to LUP
- 2016-04-01 16:13:30
- date last changed
- 2018-11-21 20:39:42
@phdthesis{896b983e-9a66-4745-a089-547cd44ab41c,
abstract = {{In this work, mathematical models have been developed describing drug release from film-coated reservoir systems as well as drug release and polymer dissolution from swelling and dissolving polymer tablets. The model derivation of both systems is based on a mechanistic approach. The model describing drug release from reservoir systems, i.e. from single, film-coated pellets, was validated against experimental release data from single ethyl-cellulose-coated pellets. The model was also expanded to account for the simultaneous release from an ensemble of single pellets, i.e. a multiple-unit model. This study was verified against release data from ensembles of ethyl-cellulose-coated pellets. Qualitative studies using SEM on the film-coated pellets together with the information gained from the model evaluation of the experimental release data, indicated that a major release mechanism from these pellets is drug transport through cracks and holes in the polymer film. This finding confirms the view that it is essential to obtain information on release characteristics on the single-unit level in order to increase our knowledge concerning release-controlling mechanisms.The model for polymer swelling and dissolution, i.e. the polymer dissolution model, and the model for drug release from a swelling and dissolving polymer matrix, i.e. the drug release model, are based on mass transfer in cylindrical geometry. Diffusive and convective contributions to mass transfer are accounted for. The polymer dissolution model was fitted to experimental polymer dissolution and front position data of the dissolution of poly (ethylene oxide). The information gained from fitting was applied to the drug release model, which was validated against drug release data for a soluble drug and a slightly soluble drug. It was concluded that the convective contribution to drug mass transfer can be of considerable importance, leading to erroneous fitting results if neglected.}},
author = {{Borgquist, Per}},
isbn = {{91-628-6374-6}},
keywords = {{swelling; XEDS; Chemical technology and engineering; Kemiteknik och kemisk teknologi; Polymer technology; biopolymers; Polymerteknik; Pharmaceutical and related technologies; Läkemedelsteknik och relaterad teknik; simulation; single pellet; single-unit release; SEM; reservoir system; poly (ethylene oxide); film-coated; matrix; mathematical model; diffusion; pellet shape; controlled release; polymer dissolution; modelling; ethyl cellulose; Coating; multiple-unit release}},
language = {{eng}},
publisher = {{KFS AB}},
school = {{Lund University}},
title = {{Modelling of Drug Release from Reservoir and Matrix Formulations - Multiple Unit Dosage Forms and Swelling and Dissolving Matrix Systems}},
year = {{2005}},
}