In vitro and in vivo characterization of long-acting aqueous suspensions – Towards a predictive semi-mechanistic pharmacokinetic model.

Nguyen, Thi Thanh Vy
Faculteit Farmaceutische Wetenschappen
Vakgroep Bioanalyse
Master of Science in Pharmaceutical Sciences – Drug development, Ghent University, Belgium, 2015 – 2017; Bachelor of Science in Pharmaceutical Sciences, Ghent University, Belgium, 2012 – 2015; Secondary education, Sciences Mathematics, Sint-Vincentiusinstituut, Dendermonde, Belgium, 2006 – 2012.
Academische graad
Doctor in de farmaceutische wetenschappen
Taal proefschrift
Vertaling titel
In vitro en in vivo karakterisatie van langwerkende waterige suspensies – Naar een voorspellend semi-mechanistisch farmacokinetisch model.
Prof. dr. An Vermeulen, UGent-Bioanalyse - dr. Jens Ceulemans, Janssen Pharmaceutica NV
Prof. dr. Chris Vervaet, UGent-Geneesmiddelenleer - Prof. dr. Katrien Remaut, UGent-Geneesmiddelenleer - Prof. Dr. Guy Van De Moorter, KU Leuven- Dr. Philippe Jacqmin, Department of Pharmacometrics, Modelling and Simulation - Dr. Stefaan Rossenu, Argenx - Dr. Bernard Van Eerdenbrugh, Janssen Pharmaceutica NV

Korte beschrijving

The overall aim of this research project was to develop a semi-mechanistic pharmacokinetic model that would be able to predict, before long-acting aqueous suspensions are tested in vivo, the in vivo drug exposure of intramuscularly administered long-acting aqueous suspensions in rats based on the input of mainly a set of well-defined in vitro and in vivo parameters, and this within a certain fold error range. The development of long-acting aqueous suspensions provides an option to address the limitations related to the increasing prevalence of poorly water-soluble drugs as new chemical entities and to reduce treatment failure in chronic diseases as well as the associated costs. However, the current development process of a long-acting aqueous suspension that achieves a certain drug release profile and duration is by trial-and-error. Unlike the more conventional dosage forms, fundamental research on the drug release mechanisms after parenteral administration of long-acting aqueous suspensions remains sparse and physiologically based in vitro models as well as predictive in silico models are inexistent or in their infancy. Predictive in vitro and in silico models would help unravel the gaps in mechanistic knowledge of the in vivo performance of parenterally administered long-acting aqueous suspensions, thereby establishing a more rational development of safe and effective formulations in the future. The subsequent research focused on the impact of relevant formulation properties on in vitro and/or in vivo drug release from long-acting aqueous suspensions by applying different aqueous suspensions varying in particle size or stabilizing excipients. Predictive in vitro and in silico models were developed and applied across aqueous suspensions of different drug compounds varying in relevant formulation properties to further elucidate the complex in vivo drug exposure of long-acting aqueous suspensions and support a more rational drug formulation development.


Dinsdag 4 oktober 2022, 18:00
Faculteit Farmaceutische Wetenschappen - Auditorium B - Andreas Vesalius, Ottergemsesteenweg 460, 9000 Gent