ECTS: 15
Vejleder: René Holm
Background of the project
Oral administration is still one of the preferred administration routes, however, as more and more compounds becomes poorly soluble a formulation challenge has hit the pharmaceutical industry. The application of enabling formulations, such as lipid based formulations and amorphous solid dispersions have largely still enabled the pharmaceutical industry to turn even poor pharmaceutical druggable molecules into drug products. However, when working with these approaches, the physical chemistry of the intestinal track may become a source of variation due to e.g. interindividual variation on bile salt concentrations, pHs or simply hydration habits that may induce a variation in the pharmacokinetic profile between patients and between days.
Higashino (2025) recent conducted a comparative analysis between compounds physical chemical parameters and the pharmacokinetic variability based upon internal data based in Towa Pharmaceuticals and reported good predictive value of the defined model. Similarily Krajcar et al. (2023) analysed Sandoz databased for clinical studies and linked the variation to BCS class, suggesting that higher variation was observed for low soluble compounds.
These studies provides good insights into expected variations, however, both was company diagnostic and generating an overview across the industry, for formulation type, physical chemical data and time could further help the pharmaceutical area to understand the area even better
Problem formulation
Is there an interlink between the formulation type and/or the BSC/DCS classification of the pharmacokinetic variation in drug products approved the last 10 years ?
Methods
The FDA and EMA databases as well as clinictrials.gov should be searched to generate a historical insight over molecules approved over the last 10 years (2015-2025) for oral administration with respect to commercial dosage form, pharmacokinetic and physical chemical data. These should be supplemented with determination of biorelevant solubilities and dissolution studies to ensure BCS/DCS classification of all compounds – which should be investigated relative to the pharmacokinetic variations reported in the clinical trials.
Analytical techniques including and high-performance liquid chromatography (HPLC), but other techniques may be relevant as well
Guidance
There will be scheduled meetings every two weeks where the student is expected to present results, interpretations and what is subsequently planned – and from here a professional discussion is taken. In addition, there will always be the possibility of ad hoc guidance meeting.
References
Higashino M. Prediction of Intra-individual Variability in Bioequivalence Studies of 278 Formulations: Comprehensive Analysis Using Physicochemical and Pharmacokinetic Parameters. Chem Pharm Bull (Tokyo). 2025;73(4):349-354. doi: 10.1248/cpb.c24-00806.
Krajcar D, Grabnar I, Jereb R, Legen I, Opara J. Predictive Potential of BCS and Pharmacokinetic Parameters on Study Outcome: Analysis of 198 In Vivo Bioequivalence Studies. Eur J Drug Metab Pharmacokinet. 2023 May;48(3):241-255. doi: 10.1007/s13318-023-00821-z