Combining optical coherence tomography and UV-vis imaging for real-time monitoring of amorphous solid dispersion dissolution

Amorphous solid dispersions (ASDs) represent an innovative solution to limited aqueous solubility in new pharmaceutical small molecules, however, the mechanisms of ASD dissolution are poorly understood. A dissolution monitoring system featuring a custom-designed flow cell, Optical Coherence Tomography (OCT) and a UV-visible dip probe in a closed loop set up was developed to monitor the structural changes on and within a dissolving Ritonavir-Soluplus ASD extrudate. With this system key structural phenomena were identified that appear to coincide with changes in dissolution behaviour. It was observed from UV-vis absorbance that overall dissolution performance decreased with increasing drug load above a threshold. In addition, above this threshold, samples displayed a delayed onset of release, the extent of the delay increasing with increasing drug load, high loading samples showed minimal release for more than 45 minutes before API concentration in the media started to increase.

By integrating OCT with the system, it was possible to observe physical changes through the sample cross section during dissolution. For all drug loadings, samples underwent an initial swelling phase. This swelling phase culminated in a delamination of the top surface of the sample. The delamination event appeared to coincide with the onset of API release, suggesting that the surface of the sample is inhibitory to API release and needs to be removed before dissolution can begin[1].

UV-vis imaging enables development of a deeper understanding of the effects of dissolution at the surface of a solid with high spatial and temporal resolution [2], while OCT allows similar monitoring of physical, structural effects at the surface and through a translucent solid[3]. These two techniques have been successfully integrated together to simultaneously monitor structural and dissolution changes at the surface of a dissolving ASD. Initial results show this technique provides better temporal correlation between delamination and release. In addition, there appears to be a relationship between delamination time and flow cell hydrodynamics.