PhD Position in Drug Delivery and Disposition Catholic University of Leuven Department of Pharmaceutical and Pharmacological Sciences

The work will be performed in the Drug Delivery and Disposition research group (Department of Pharmaceutical and Pharmacological Sciences; KU Leuven) under the direct supervision of Prof. G. Van den Mooter (https://www.kuleuven.be/wieiswie/nl/person/00006817). KU Leuven is one of the top 50 universities in the world (top 10 in Europe) according to the "Times Higher Education" ranking, and ranks #7 (top in Europe) in the "World’s Most Innovative Universities" ranking elaborated by Reuters. KU Leuven offers an exciting multi-disciplinary research environment, a broad range of training courses for PhD students, and full social and medical insurance. Responsibilities The number of new chemical entities (NCEs) in the pipeline of pharmaceutical industry that display unfavorable water solubility, is in constant growth. As the development of these poorly water-soluble compounds is generally constrained due to a reduced absorption and hence reduced oral bioavailability, solubility enhancing formulation approaches are generally required. In this respect, amorphous solid dispersions (ASDs) have become a common formulation strategy to overcome the solubility issue and improve the drug absorption. Chiou and Riegelman (1971) were the first to define the term “solid dispersion” as “a dispersion of one or more active ingredients in an inert carrier at the solid state, prepared by the melting, the solvent, or the melting solvent method”. Despite the advantages solid dispersions offer regarding dissolution rate and solubility, physical stability of amorphous formulations during storage (i.e. amorphous phase separation and conversion of amorphous into crystalline material) impedes their development and commercial success. The inherent instability of ASD formulations is a complex process which results from the combination of thermodynamic considerations (miscibility of the blend and solubility of the API in the polymer matrix), kinetic factors (Tg, molecular mobility,inter-molecular interactions and presence of seed materials), manufacturing (downstream) processes and storage conditions (influence of temperature and humidity). This complexity together with the lack of understanding of the basic physics of the amorphous state makes that, despite significant research efforts in this area, a prediction of long-term stability of amorphous formulations remains with limited success. In order to accomplish optimum stability, the choice of a suitable carrier is essential in the kinetic stabilization of the amorphous drug. A general rule of thumb is that the molecular mobility of an amorphous system can be neglected at a temperature of 50°C below the Tg of the mixture. However recent advanced research pointed out the influence of local mobility called β-relaxation process in the physical stability of pure amorphous drugs. This finding confirms the importance of molecular mobility as a relevant parameter with respect to the crystallization process and brings up the need to explore in a systematic way the β-transition, or more in general, sub-Tg transitions or relaxation processes of ASD systems and to evaluate how it translates in terms of long-term stability of amorphous formulations. The objectives of the study are: To determine the Tgα and Tgβ of a set of solid dispersions made up of model drug and polymer To investigate the evolution of Tgβ as a function of drug-loading (by DMA, DES) To explore the difference and significance in Tgα and Tgβ obtained from different analytical techniques (i.e. mDSC, DMA, DES) To characterize the relaxation process (α and β) of the model solid dispersions as function of time and temperature * To determine the onset of physical instability (i.e. phase separation, onset of crystallization) of the solid dispersions under stressed conditions (temperature and humidity) To explore the relationship between β-relaxation process and physical stability (related to ) To investigate polymer-API miscibility/intimacy with Solid State NMR/relaxometry and phase diagrams of the polymer-API combinations. Profile* Profile: PhD in physical chemistry (polymer chemistry, polymer physics) or other relevant experience in this domain. Communication skills: Ability to work both independently and in a team, direct communication style. Fluency in spoken and written English is mandatory! Offer We offer a fulltime position for 2 years (starting as from January, 2021) in a stimulating environment at a top European university in a well-equiped, experienced and internationally oriented research unit. You will be based at the Department of Pharmaceutical and Pharmacological Sciences at the Gasthuisberg Campus in Leuven. Interested? For more information please contact Prof. dr. Guy Van den Mooter, tel.: +32 16 33 03 04, mail: guy.vandenmooter@kuleuven.be. You can apply for this job no later than November 01, 2020 via the KU Leuven seeks to foster an environment where all talents can flourish, regardless of gender, age, cultural background, nationality or impairments. If you have any questions relating to accessibility or support, please contact us at diversiteit.HR@kuleuven.be. Employment percentage: Voltijds Location: Leuven Apply before: November 1, 2020 Tags: Farmaceutische en Farmacologische Wetenschappen If you apply for this position please say you saw it on Medicinoxy Apply

The work will be performed in the Drug Delivery and Disposition research group (Department of Pharmaceutical and Pharmacological Sciences; KU Leuven) under the direct supervision of Prof. G. Van den Mooter (https://www.kuleuven.be/wieiswie/nl/person/00006817). KU Leuven is one of the top 50 universities in the world (top 10 in Europe) according to the "Times Higher Education" ranking, and ranks #7 (top in Europe) in the "World’s Most Innovative Universities" ranking elaborated by Reuters. KU Leuven offers an exciting multi-disciplinary research environment, a broad range of training courses for PhD students, and full social and medical insurance.

Responsibilities

The number of new chemical entities (NCEs) in the pipeline of pharmaceutical industry that display unfavorable water solubility, is in constant growth. As the development of these poorly water-soluble compounds is generally constrained due to a reduced absorption and hence reduced oral bioavailability, solubility enhancing formulation approaches are generally required. In this respect, amorphous solid dispersions (ASDs) have become a common formulation strategy to overcome the solubility issue and improve the drug absorption. Chiou and Riegelman (1971) were the first to define the term “solid dispersion” as “a dispersion of one or more active ingredients in an inert carrier at the solid state, prepared by the melting, the solvent, or the melting solvent method”.

Despite the advantages solid dispersions offer regarding dissolution rate and solubility, physical stability of amorphous formulations during storage (i.e. amorphous phase separation and conversion of amorphous into crystalline material) impedes their development and commercial success. The inherent instability of ASD formulations is a complex process which results from the combination of thermodynamic considerations (miscibility of the blend and solubility of the API in the polymer matrix), kinetic factors (Tg, molecular mobility,inter-molecular interactions and presence of seed materials), manufacturing (downstream) processes and storage conditions (influence of temperature and humidity). This complexity together with the lack of understanding of the basic physics of the amorphous state makes that, despite significant research efforts in this area, a prediction of long-term stability of amorphous formulations remains with limited success.

In order to accomplish optimum stability, the choice of a suitable carrier is essential in the kinetic stabilization of the amorphous drug. A general rule of thumb is that the molecular mobility of an amorphous system can be neglected at a temperature of 50°C below the Tg of the mixture. However recent advanced research pointed out the influence of local mobility called β-relaxation process in the physical stability of pure amorphous drugs. This finding confirms the importance of molecular mobility as a relevant parameter with respect to the crystallization process and brings up the need to explore in a systematic way the β-transition, or more in general, sub-Tg transitions or relaxation processes of ASD systems and to evaluate how it translates in terms of long-term stability of amorphous formulations.

The objectives of the study are:

To determine the Tgα and Tgβ of a set of solid dispersions made up of model drug and polymer
To investigate the evolution of Tgβ as a function of drug-loading (by DMA, DES)
To explore the difference and significance in Tgα and Tgβ obtained from different analytical techniques (i.e. mDSC, DMA, DES)
To characterize the relaxation process (α and β) of the model solid dispersions as function of time and temperature *
To determine the onset of physical instability (i.e. phase separation, onset of crystallization) of the solid dispersions under stressed conditions (temperature and humidity)
To explore the relationship between β-relaxation process and physical stability (related to *)
To investigate polymer-API miscibility/intimacy with Solid State NMR/relaxometry and phase diagrams of the polymer-API combinations.

Profile

Profile: PhD in physical chemistry (polymer chemistry, polymer physics) or other relevant experience in this domain.
Communication skills: Ability to work both independently and in a team, direct communication style. Fluency in spoken and written English is mandatory!

Offer

We offer a fulltime position for 2 years (starting as from January, 2021) in a stimulating environment at a top European university in a well-equiped, experienced and internationally oriented research unit. You will be based at the Department of Pharmaceutical and Pharmacological Sciences at the Gasthuisberg Campus in Leuven.

Interested?

For more information please contact Prof. dr. Guy Van den Mooter, tel.: +32 16 33 03 04, mail: guy.vandenmooter@kuleuven.be.

You can apply for this job no later than November 01, 2020 via the

KU Leuven seeks to foster an environment where all talents can flourish, regardless of gender, age, cultural background, nationality or impairments. If you have any questions relating to accessibility or support, please contact us at diversiteit.HR@kuleuven.be.

Employment percentage: Voltijds
Location: Leuven
Apply before: November 1, 2020
Tags: Farmaceutische en Farmacologische Wetenschappen

If you apply for this position please say you saw it on Medicinoxy

Apply