Comparative Drug Solubility Studies Using Shake-Flask Versus a Laser-Based Robotic Method

Drug solubility is of central importance to the pharmaceutical sciences, but reported values often show discrepancies. Various factors have been discussed in the literature to account for such differences, but the influence of manual testing in comparison to a robotic system has not been studied adequately before. In this study, four expert researchers were asked to measure the solubility of four drugs with various solubility behaviors (i.e., paracetamol, mesalazine, lamotrigine, and ketoconazole) in the same laboratory with the same instruments, method, and material sources and repeated their measurements after a time interval. In addition, the same solubility data were determined using an automated laser-based setup. The results suggest that manual testing leads to a handling influence on measured solubility values, and the results were discussed in more detail as compared to the automated laser-based system. Within the framework of unavoidable uncertainties of solubility testing, it is a possibility to combine minimal experimental testing that is preferably automated with mathematical modeling. That is a practical suggestion to support future pharmaceutical development in a more efficient way.