Automating Aqueous Compound Solubility Using the 96-Well Multiscreen® Solubility Filter Plate on a Hamilton Microlab® Star Workstation

Determining aqueous compound solubility has become an essential tool in the early stages of the drug discovery process. Solubility of a compound is important in the Biopharmaceutics Classification System (BCS). BCS classifies compounds based on their solubility and permeability. Low solubility can lead to unreliable results during in-vitro testing. Also, insoluble precipitates have been shown to cause false positives in bioassays, wasting valuable time and resources. Such issues will typically add significant cost to drug research projects. In addition to these factors, the standard shake-flask method used to evaluate drug solubility is inherently low throughput and labor intensive.

Here we describe an automated method for determining drug solubility using Millipore’s MultiScreen Solubility filter plate on the Hamilton MICROLAB STAR workstation. The procedure requires minimal manual intervention by utilizing the iSWAP for all plate movements on the deck, but vacuuming occurs offline. The vacuuming occurs off-line because the Hamilton’s Automated Vacuum System does not have a support grid needed for the MultiScreen Solubility plate. Eight compounds were tested in twelve replicates and the results were compared to those achieved through the manual method to demonstrate the viability of the automated protocol. It takes about 1 hour and 48 minutes to process one plate of 96 samples (this includes 90 minute shaking on the deck with a VARIOMAG® shaker). This translates to about six or more plates being able to be processed in a standard 8-hour day.