Ranking in vitro dissolution rate of poorly soluble orally inhaled powders

Aim of study:
The aim is to rank the in vitro dissolution of poorly soluble orally inhaled powders using two different apparatuses

After lung deposition, rapidly dissolving and permeating drug substance (DS) will be minimally influenced by mucociliary clearance and will thus be absorbed almost completely. For poorly soluble DSs however, pulmonary dissolution may rate-limit absorption after lung deposition and consequently influence clinical performance (e.g. safety, efficacy and duration of treatment).

Consequently, it is important to characterize the dissolution rate of poorly soluble DSs during inhaled drug development.

Furthermore, the in vitro dissolution rate may function as a critical quality attribute (CQA) and thus be monitored in addition to e.g. solubility, particle size and amorphicity.

Practically, in vitro dissolution of orally inhaled powders often requires proper dispersion of DS particles prior to dissolution. In vitro dissolution of poorly soluble DSs often requires the addition of surfactants to maintain sink conditions during dissolution. Manual sampling may also be required with subsequent DS quantification using UPLC-UV.

We believe that by using two new apparatuses we can implement on-line DS quantification and/or auto-sampling, thus increasing the frequency by which dissolution-profiles can be generated.

The Master-thesis work will revolve around in vitro dissolution of poorly soluble drug substances by using two different apparatuses and methods. UPLC-UV will be used for quantification of concentrations and a report is to be written in English.

Last date to submit your application is April 15th. For questions please contact Frans Franek, PhD, Senior Scientist Biopharmaceutics Inhalation, PT&D. E-mail: frans.franek@astrazeneca.com