Searching for physiologically relevant in vitro dissolution techniques for orally inhaled drugs

Snezana Radivojev, Sarah Zellnitz, Amrit Paudel, Eleonore Froehlich

Publikation: Beitrag in einer FachzeitschriftReview eines Fachbereichs (Review article)ForschungBegutachtung

Abstract

Inhalation is the preferred route for the treatment of lung diseases. More recently, also formulations for systemic treatment have been developed. For efficient development of inhalation products it is necessary to identify a link between particle parameters and in vivo performance. Such a relation exists for oral drugs where dissolution and permeation across Caco-2 monolayers are correlated to in vivo absorption. By contrast, the only in vitro parameter with established link to absorption for inhalation is particle size. In vitro dissolution could be another important parameter because low solubility determines bioavailability of inhaled drugs. The review highlights the importance of dissolution for drug availability in general and lists important differences in dissolution testing of oral and inhaled formulations. Dissolution testing protocols are summarized with focus on the composition of the various fluids, which are used to mimic particle dissolution in the deep lung. Finally, a role of in silico modelling in identification of physiologically relevant dissolution fluids and in in vitro in vivo correlation is suggested.
Originalspracheenglisch
Seiten (von - bis)45-56
Seitenumfang12
FachzeitschriftInternational Journal of Pharmaceutics
Jahrgang556
DOIs
PublikationsstatusVeröffentlicht - 10 Feb 2019

Fingerprint

Inhalation
Pharmaceutical Preparations
Particle Size
Computer Simulation
Solubility
Biological Availability
Lung Diseases
Lung
In Vitro Techniques
Drug Liberation

Schlagwörter

    ASJC Scopus subject areas

    • !!Pharmaceutical Science

    Dies zitieren

    Searching for physiologically relevant in vitro dissolution techniques for orally inhaled drugs. / Radivojev, Snezana; Zellnitz, Sarah; Paudel, Amrit; Froehlich, Eleonore .

    in: International Journal of Pharmaceutics, Jahrgang 556, 10.02.2019, S. 45-56.

    Publikation: Beitrag in einer FachzeitschriftReview eines Fachbereichs (Review article)ForschungBegutachtung

    @article{e4e76f1ec5af4fd089f4cef96c1b55aa,
    title = "Searching for physiologically relevant in vitro dissolution techniques for orally inhaled drugs",
    abstract = "Inhalation is the preferred route for the treatment of lung diseases. More recently, also formulations for systemic treatment have been developed. For efficient development of inhalation products it is necessary to identify a link between particle parameters and in vivo performance. Such a relation exists for oral drugs where dissolution and permeation across Caco-2 monolayers are correlated to in vivo absorption. By contrast, the only in vitro parameter with established link to absorption for inhalation is particle size. In vitro dissolution could be another important parameter because low solubility determines bioavailability of inhaled drugs. The review highlights the importance of dissolution for drug availability in general and lists important differences in dissolution testing of oral and inhaled formulations. Dissolution testing protocols are summarized with focus on the composition of the various fluids, which are used to mimic particle dissolution in the deep lung. Finally, a role of in silico modelling in identification of physiologically relevant dissolution fluids and in in vitro in vivo correlation is suggested.",
    keywords = "In vitro dissolution, Oral inhalation, Simulated lung fluid, Dissolution testing, Inhalation treatment, PBPK modelling",
    author = "Snezana Radivojev and Sarah Zellnitz and Amrit Paudel and Eleonore Froehlich",
    year = "2019",
    month = "2",
    day = "10",
    doi = "10.1016/j.ijpharm.2018.11.072",
    language = "English",
    volume = "556",
    pages = "45--56",
    journal = "International Journal of Pharmaceutics",
    issn = "0378-5173",
    publisher = "Elsevier B.V.",

    }

    TY - JOUR

    T1 - Searching for physiologically relevant in vitro dissolution techniques for orally inhaled drugs

    AU - Radivojev, Snezana

    AU - Zellnitz, Sarah

    AU - Paudel, Amrit

    AU - Froehlich, Eleonore

    PY - 2019/2/10

    Y1 - 2019/2/10

    N2 - Inhalation is the preferred route for the treatment of lung diseases. More recently, also formulations for systemic treatment have been developed. For efficient development of inhalation products it is necessary to identify a link between particle parameters and in vivo performance. Such a relation exists for oral drugs where dissolution and permeation across Caco-2 monolayers are correlated to in vivo absorption. By contrast, the only in vitro parameter with established link to absorption for inhalation is particle size. In vitro dissolution could be another important parameter because low solubility determines bioavailability of inhaled drugs. The review highlights the importance of dissolution for drug availability in general and lists important differences in dissolution testing of oral and inhaled formulations. Dissolution testing protocols are summarized with focus on the composition of the various fluids, which are used to mimic particle dissolution in the deep lung. Finally, a role of in silico modelling in identification of physiologically relevant dissolution fluids and in in vitro in vivo correlation is suggested.

    AB - Inhalation is the preferred route for the treatment of lung diseases. More recently, also formulations for systemic treatment have been developed. For efficient development of inhalation products it is necessary to identify a link between particle parameters and in vivo performance. Such a relation exists for oral drugs where dissolution and permeation across Caco-2 monolayers are correlated to in vivo absorption. By contrast, the only in vitro parameter with established link to absorption for inhalation is particle size. In vitro dissolution could be another important parameter because low solubility determines bioavailability of inhaled drugs. The review highlights the importance of dissolution for drug availability in general and lists important differences in dissolution testing of oral and inhaled formulations. Dissolution testing protocols are summarized with focus on the composition of the various fluids, which are used to mimic particle dissolution in the deep lung. Finally, a role of in silico modelling in identification of physiologically relevant dissolution fluids and in in vitro in vivo correlation is suggested.

    KW - In vitro dissolution

    KW - Oral inhalation

    KW - Simulated lung fluid

    KW - Dissolution testing

    KW - Inhalation treatment

    KW - PBPK modelling

    UR - http://www.scopus.com/inward/record.url?scp=85058188693&partnerID=8YFLogxK

    U2 - 10.1016/j.ijpharm.2018.11.072

    DO - 10.1016/j.ijpharm.2018.11.072

    M3 - Review article

    VL - 556

    SP - 45

    EP - 56

    JO - International Journal of Pharmaceutics

    JF - International Journal of Pharmaceutics

    SN - 0378-5173

    ER -