Characterisation of colloidal structures and their solubilising potential for BCS class II drugs in fasted state simulated intestinal fluid

A suite of fasted state simulated intestinal fluid (SIF), based on variability observed in a range of fasted state human intestinal fluid (HIF) samples was used to study the solubility of eight poorly soluble drugs (three acidic drugs (naproxen, indomethacin and phenytoin), two basic drugs (carvedilol and tadalafil) and three neutral drugs (felodipine, fenofibrate, griseofulvin)). Particle size of the colloidal structures formed in these SIF in the presence and absence of drugs was measured using dynamic light scattering and nanoparticle tracking analysis.

Results indicate that drug solubility tends to increase with increasing total amphiphile concentration (TAC) in SIF with acidic drugs proving to be more soluble than basic or neutral drug in the media evaluated. Dynamic light scattering showed that as the amphiphile concentration increased, the hydrodynamic diameters of the structures decreased. The scattering distribution confirmed the polydispersity of the simulated intestinal fluids compared to the monodisperse distribution observed for FaSSIF v1). There was a large difference in the size of the structures found based on the composition of the SIF, for example, the diameter of the structures measured in felodipine in the minimum TAC media was measured to be 170 ± 5 nm which decreased to 5.1 ± 0.2 nm in the maximum TAC media point. The size measured of the colloidal structures of felodipine in the FaSSIF v1 was 86 ± 1 nm. However, there was no simple correlation between solubility and colloidal size.

Nanoparticle tracking analysis was used for the first time to characterise colloidal structures within SIF and the results were compared to those obtained by dynamic light scattering. The particle size measured by dynamic light scattering was generally greater in media with a lower concentration of amphiphiles and smaller in media of a higher concentration of amphiphiles, compared to that of the data yielded by nanoparticle tracking analysis.

This work shows that the colloidal structures formed vary depending on the composition of SIF which affects the solubility. Work is ongoing to determine the relationship between colloidal structure and solubility.