Logotyp: till Uppsala universitets webbplats

uu.sePublikationer från Uppsala universitet
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Model for the Analysis of Membrane-Type Dissolution Tests for Inhaled Drugs
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.ORCID-id: 0000-0003-4013-9704
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.ORCID-id: 0000-0001-8327-6755
AstraZeneca, Inhaled Prod Dev Pharmaceut Technol & Dev, S-43183 Gothenburg, Sweden..
AstraZeneca, Adv Drug Delivery, Pharmaceut Sci, R&D, S-43183 Gothenburg, Sweden..
Visa övriga samt affilieringar
2020 (Engelska)Ingår i: Molecular Pharmaceutics, ISSN 1543-8384, E-ISSN 1543-8392, Vol. 17, nr 7, s. 2426-2434Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Impactor-type dose deposition is a common prerequisite for dissolution testing of inhaled medicines, and drug release typically takes place through a membrane. The purpose of this work is to develop a mechanistic model for such combined dissolution and release processes, focusing on a drug that initially is present in solid form. Our starting points are the Noyes-Whitney (or Nernst-Brunner) equation and Fick's law. A detailed mechanistic analysis of the drug release process is provided, and approximate closed-form expressions for the amount of the drug that remains in solid form and the amount of the drug that has been released are derived. Comparisons with numerical data demonstrated the accuracy of the approximate expressions. Comparisons with experimental release data from literature demonstrated that the model can be used to establish rate-controlling release mechanisms. In conclusion, the model constitutes a valuable tool for the analysis of in vitro dissolution data for inhaled drugs.

Ort, förlag, år, upplaga, sidor
AMER CHEMICAL SOC , 2020. Vol. 17, nr 7, s. 2426-2434
Nyckelord [en]
drug delivery, dissolution, lung, mathematical model, formulation development
Nationell ämneskategori
Farmaceutiska vetenskaper
Identifikatorer
URN: urn:nbn:se:uu:diva-419691DOI: 10.1021/acs.molpharmaceut.0c00163ISI: 000548455300017PubMedID: 32463245OAI: oai:DiVA.org:uu-419691DiVA, id: diva2:1470444
Tillgänglig från: 2020-09-24 Skapad: 2020-09-24 Senast uppdaterad: 2023-02-28Bibliografiskt granskad
Ingår i avhandling
1. Characterisation of an in vitro dissolution method for assessment of novel pulmonary drug delivery systems: With a focus on controlled release systems
Öppna denna publikation i ny flik eller fönster >>Characterisation of an in vitro dissolution method for assessment of novel pulmonary drug delivery systems: With a focus on controlled release systems
2023 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Pulmonary drug delivery has been used for decades to treat local diseases like asthma. When using the pulmonary route to deliver drugs, several important lung features are being used, such as a large surface area available for absorption, high organ vascularization, and a thin blood-alveolar barrier. Pulmonary drug delivery systems on the market are formulations with a rapid release, which leads to a high drug concentration initially and a prompt decline in concentration shortly thereafter. This could cause unfavourable adverse effects or toxicity to the lung tissue at the onset of the release and could also result in decreased efficacy. To overcome these challenges, there is a need to develop controlled release drug delivery systems to improve the therapeutic effectiveness of inhaled drugs. When a drug is inhaled, the drug particles will deposit in the lung, and the drug needs to dissolve in the lung fluids before the drug is available for uptake locally or in the systemic circulation. The absorption inhaled drug thus depends on the dissolution of the drug particles in the lung fluid. As a result, it could be possible to prolong the duration of the drug effect, by prolonging the time it takes for the dissolution of the drug particles. Due to this, in vitro methods analysing the dissolution of the drug particles in the lung are of high relevance for the development of novel pulmonary drug delivery systems. It is therefore of high importance that the dissolution profiles that are measured are well understood. The overall aim of this thesis was to evaluate and characterise an in vitro dissolution method (Transwell system) for assessment of novel pulmonary drug delivery systems, with a focus on future controlled release systems. A developed mechanistic model was used to analyse experimental dissolution data and to predict which process was the rate limiting step in the obtained profiles. The developed mechanistic model provided the same rank order as the Weibull fit, however the model provided additional detailed understanding of the used dissolution process and setup. In addition, two novel controlled release drug delivery systems, mesoporous silica particles and hyaluronic based hydrogels, were successfully analysed using this in vitro dissolution system. Both delivery systems showed a promising aerosolization and control over the release profiles. Finally, the micellar contribution to diffusion of poorly soluble inhaled drugs during in vitro dissolution was defined and validated using the obtained in vitro dissolution profiles. Physiologically based biopharmaceutics modelling tools were successfully established for Bud, BDP and FP using the diffusivity values taking into account the micellar contribution of the surfactant.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2023. s. 59
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 327
Nyckelord
Pulmonary drug delivery, in vitro dissolution, mechanistic model, controlled release, physiologically based biopharmaceutics modelling
Nationell ämneskategori
Farmaceutiska vetenskaper
Identifikatorer
urn:nbn:se:uu:diva-497535 (URN)978-91-513-1733-5 (ISBN)
Disputation
2023-04-21, Room A1:107a, BMC, Husargatan 3, Uppsala, 09:15 (Engelska)
Opponent
Handledare
Tillgänglig från: 2023-03-30 Skapad: 2023-02-28 Senast uppdaterad: 2023-03-30

Open Access i DiVA

fulltext(2206 kB)660 nedladdningar
Filinformation
Filnamn FULLTEXT01.pdfFilstorlek 2206 kBChecksumma SHA-512
11cbe12fcdb4cd0180dc9ed652c00d45eb9cb8df700480c6cbd9db83f1723218b631232e0bb8ffd94b777191689be29eb3469fe3866c5ba39e642e600e6e246c
Typ fulltextMimetyp application/pdf

Övriga länkar

Förlagets fulltextPubMed

Person

Frenning, Göranvan der Zwaan, Ires

Sök vidare i DiVA

Av författaren/redaktören
Frenning, Göranvan der Zwaan, Ires
Av organisationen
Institutionen för farmaceutisk biovetenskap
I samma tidskrift
Molecular Pharmaceutics
Farmaceutiska vetenskaper

Sök vidare utanför DiVA

GoogleGoogle Scholar
Totalt: 661 nedladdningar
Antalet nedladdningar är summan av nedladdningar för alla fulltexter. Det kan inkludera t.ex tidigare versioner som nu inte längre är tillgängliga.

doi
pubmed
urn-nbn

Altmetricpoäng

doi
pubmed
urn-nbn
Totalt: 289 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf