An in vitro kinetic method for detection of precipitation of poorly soluble drugs

In-vitro prediction of bioavailability following extravascular injection of poorly soluble drugs: an insight into clinical failure and the role of delivery systems

“…Overall, the in‐vitro data correlate well with the intramuscular/subcutaneous absorption reported during clinical evaluations and animal experiments with six poorly soluble drugs in nine formulations (Table ). The results also suggest that the in‐vitro model can be used to indicate not only the possibility but also the degree of precipitation (measured as OD), which potentially occurs upon injection, as shown with CBZ.…”

“…Except for the pH‐controlled CD formulation of PTN, which resulted in the highest precipitation (OD at 500 nm = 1.267 ± 0.061; DF 0.75) as shown in Figure , all formulations solubilized using CD alone resulted in no precipitation compared with both co‐solvent and mixed co‐solvent/complexation formulations. However, overnight crystal formation in CD formulations at less dilution (DF 0.75) was observed, despite the fact that the 96‐well plate was covered to minimize solvent evaporation, possibly due to the inhibitory effect of CD on crystal formation …”

“…The tissue damage induced by drug precipitation was circumvented by the use of HP‐β‐CD even though most of the RBZ in the formulation (94.6%) was not complexed . Previous in‐vitro studies suggested that while the low pH RBZ aqueous solutions readily precipitated on dilution with buffer, addition of HP‐β‐CD produced a concentration‐dependent inhibition to the drug precipitation by maintaining the mixture as a supernatant solution for long time …”

“…The method first reported by Wu et al . in 2005 is based on a 96‐well plate and needs minimal amounts of drug substance and formulation. The programmatic monitoring of the OD by a microplate reader can be tailored according to the purpose of study, and maximum OD and T max (time to reach maximum OD) can be determined.…”

“…The programmatic monitoring of the OD by a microplate reader can be tailored according to the purpose of study, and maximum OD and T max (time to reach maximum OD) can be determined. It was found that the lower the wavelength for detection, the more sensitive the method is (500–600 nm) …”