Surfactants enhance recovery of poorly soluble drugs during microdialysis sampling: Implications for in vitro dissolution-/permeation-studies
Aim of this project was to investigate the applicability of a recently developed in vitro microdialysis-sampling approach in connection with a dissolution-/permeation (D/P) system, especially the impact of surfactants within the perfusion fluid. The D/P-system is based on side-by-side chambers, separated by a barrier that simulates the intestinal barrier. Here, in contrast to conventional D/P-systems, the dissolution of the drug (donor chamber concentration) is followed by microdialysis sampling. This approach appears promising, because it is expected not to disturb the dynamic interplay between drug-dissolution (-release) and drug permeation. Furthermore, it should allow quantification of the unbound (free) drug concentration. In the first step, it was assessed, if the addition of the anionic surfactant sodium dodecyl sulphate (SDS) to the perfusate of the microdialysis system affects the recovery of the (slightly) water-soluble model drug acyclovir and the poorly water soluble model drug celecoxib (CXB). SDS had no influence on acyclovir-recovery, but substantially enhanced CXB-recovery, partly due to improved extraction efficiency, partly due to inhibition of loss of CXB due to non-specific binding to surfaces and the probe. The fraction of CXB recovered from aqueous CXB-solutions by microdialysis sampling using SDS-containing perfusates correlated well with the celecoxib concentration in the samples, but was found independent of the SDS-concentrations (above critical micelle concentration). In the next step microdialysis sampling with SDS-containing perfusates was assessed for celecoxib solutions in fasted state simulated intestinal fluid (FaSSIF) and compared to that in buffer. In FaSSIF, the measured CXB-concentrations were far below the overall CXB concentration, likely representing the free celecoxib, i.e. the fraction of drug, which is not associated with taurocholate surfactant micelles. In buffer, the measured concentrations matched the overall CXB concentrations. By the use of SDS-containing perfusates microdialysis sampling enabled reliable quantification of minute amounts of free CXB, which renders its use promising for dissolution-/permeation experiments with other poorly soluble drugs.