Imaging of Calcium chloride drug dissolution by single molecule microscopy

The most common mode of drug delivery - Oral administration, brings with it an uncertainty in the variation of bioavailability of the drug. This is a common problem faced by the pharmaceutical industry. Current in-vivo models for drug dissolution are based on the phenomenological Whitney-Noyes equation. They generate inconsistent results because they ignore the heterogeneities of dissolution at the molecular level, among other reasons. This research aims to unveil heterogeneities of dissolution at the molecular level. Total internal reflection fluorescence microscopy (TIRF) is used to image the dissolution of CaCl2 (active pharmaceutical ingredient or API) in water at the single molecule level. The change in "turn-on" events as agarose-CaCl2 composite film dissolves in aqueous Rhod-2 solution is observed over time. The size of these events with respect to the entire image frame is also computed. These techniques allow for detecting changes in the concentration of aqueous Ca2+ during the dissolution process, and to quantify the heterogeneities respectively. This proof-of-principle single molecule detection method will be used to develop a pharmacokinetic model for molecular drug dissolution.