Application of a light scattering microtiter plate-based method for the detection of the excipient-mediated drug precipitation inhibition
Inhibition of drug precipitation using excipients is classically determined by the quantification of the dissolved compound in the solution. Herein, a light scattering microtiter plate-based method based on the quantification of the compound precipitate was used for this purpose as an alternative methodology.By measuring light scattering in supersaturated solution the screening of 23 excipients on the precipitation inhibition of poorly soluble fenofibrate and dipyridamole was performed.The light scattering method resulted in excellent correlation (r>0.91) between the calculated precipitation inhibitor parameters (PIPs) and the precipitation inhibition index (PIclassical) obtained by the classical approach for fenofibrate and dipyridamole. Among the evaluated PIPs, AUC100 resulted in only four false positives and lack of false negatives. In conclusion, the light scattering-based method could be reliably used for identification of novel precipitation inhibitors as a first screening tool in formulation development processes.
AUC – area under curve
Fa/FeSSIF – fasted/fed state simulated intestinal fluid
GIT – gastrointestinal tract
HTE – high throughput experimentation
PI – precipitation inhibition index
PIclassical – precipitation inhibition index determined
by the classical approach
PIPs – precipitation inhibition parameters
RNU – relative nephelometric unit
RNUmax – maximum relative nephelometric unit
UPLC – ultra pressure liquid chromatography
A sufficient drug oral bioavailability followed by the desired clinical efficacy is of critical importance for the positive outcome of drug discovery and formulation development projects (1). The improvement of oral bioavailability by proper formulation design has gained importance and is now recognized as a powerful tool, not just in early drug development formulation design, but also in the later stages of drug discovery. In the past several years, research groups and drug discovery units have developed high-throughput experimental (HTE) technique ...