Resolving drug release mechanisms of amorphous solid dispersions during dissolution using optical coherence tomography

Amorphous Solid Dispersions (ASDs) are a drug delivery system for enhancing the dissolution poorly water soluble drugs [1]. The project Digital Design and Manufacture of Amorphous Pharmaceuticals aims to characterize the mechanisms of drug release from ASDs during dissolution. Optical Coherence Tomography (OCT) is a contact free, non-destructive imaging technique based on low-coherence interferometry [2]. OCT allows the collection of high-quality images that penetrate beneath the surface of an object. The objective of this work is to utilize OCT to image amorphous extrudates during dissolution to analyse swelling and liquid absorption of the polymer.

In this study, dissolution of Hot Melt Extruded (HME) ASDs was conducted using a novel flow cell. Liquid absorption and swelling mechanisms were analysed using OCT. Previous work in the pharmaceutical space has used OCT for imaging dry tablets [2]. Utilizing OCT for in-line dissolution analysis represents a new application of this technology. OCT images collected from dissolving extrudate show swelling and liquid absorption which can be tracked by applying a Random Forest machine learning algorithm.

Liquid penetration appears to be a quicker process than swelling in these samples due to dissolution at the swelling front. Application of OCT to amorphous extrudates can highlight features in the internal structure post-manufacture and some structural changes that occur during dissolution with detailed resolution to a depth of 1 mm. OCT is a powerful tool for in- situ analysis of ASD dissolution, with the collection of high-quality data that penetrates deep into the ASD extrudate.