New biphasic system in side-by-side chambers for testing drug dissolution and permeation in vitro (BiDP system)

This study aims to develop a new in vitro system for evaluating oral absorbability of drugs or drug candidates from solid, especially of poorly water-soluble compounds. The system, named Biphasic Dissolution and Permeation system (BiDP system), was designed based on previously developed in vitro systems for improving their throughput and the predictability, one is a Dissolution/Permeation system developed in our laboratory (Kataoka et al., 2003) and another is a Biphasic system (Shi et., 2010). BiDP system consists of side-by-side chambers for donor and receiver, and octanol was used as a receiver fluid to accept the drugs according to the lipophilicity. Solid drugs were applied to the donor side which were filled with simulated fasted state or fed state intestinal fluid (FaSSIF or FeSSIF) and the permeated amounts of the drug to the receiver side was determined. To separate the donor and receiver fluid, hydrophilic filter was equipped between chambers. As a filter, Duropre filter (MERCK Millipore, MA, USA) with smaller pore size (0.1 or 0.2 mu m) was found to be most appropriate for this system, since it can work as an unstirred water layer at the border of aqueous and octanol phase. To check the predictability of BiDP system for oral drug absorption, 8 drugs with diverse physicochemical properties were used and tested for their dissolution in the donor side and permeation to the receiver side. Sigmoidal correlations were obtained between permeated amounts/2 h in BiDP system and in vivo absorption in human (Fraction dose absorbed, Fa). By using this correlation as a standard curve, Fa of tested drugs were predicted. The predictability of BiDP system was found to be equal to or better than the existing D/P system. Since BiDP system does not require the cell culture process, this system was expected to enable a simple and high throughput screening of oral absorbability of drugs or drug candidates at the early stage of development.

Automated summary

This study developed a new in vitro system called BiDP system to evaluate the oral absorbability of solid drugs, utilizing side-by-side chambers with octanol as the receiver fluid and a hydrophilic filter to separate the donor and receiver fluids. The predictability of the system was shown to be equal to or better than existing in vitro systems, making it a promising tool for high throughput screening of oral absorbability of drugs or drug candidates at an early stage of development.