Study of a Standardized Taurocholate– Lecithin Powder for Preparing the Biorelevant Media FeSSIF and FaSSIF

The properties of taurocholate–lecithin powder (SIF Powder) and the biorelevant media FeSSIF and FaSSIF prepared from the powder were investigated using various techniques. The powder is stable and shows no change in the physical or chemical characteristics for at least 12 months in the original container stored at 2–8 °C. FeSSIF and FaSSIF were stable with respect to hydrolysis for at least 48 h at 37 °C. Oxidation in FeSSIF was detected at a very low level and to an even lower extent in FaSSIF. FaSSIF comprises a complex mixture of colloidal aggregates including rod-like, spherical, disc-like mixed micelles and vesicles. Consistent particle size was achieved by equilibrating the medium at room temperature (RT) after preparation. In comparison, FeSSIF only comprises smaller mixed micelles and requires no equilibration. The dissolution rates of three poorly water-soluble model drugs tested in FaSSIF media differing in average particle size controlled at 30 nm and 50 nm were not statistically different. However, differences in the average particle size can affect visual clarity: FaSSIF is generally slightly opalescent above an average size of approximately 50 nm and appears clear below approximately 50 nm. Challenge tests showed that FaSSIF is more susceptible to microbial spoilage than FeSSIF. Reproducible FeSSIF and FaSSIF can be made conveniently from the powder by employing standard preparation methods at RT. INTRODUCTION Simulated small intestinal biorelevant media are increasingly seen as a helpful tool to assess the dissolution and solubility of drugs. Fasted-state simulated intestinal fluids (FaSSIF) and fed-state simulated intestinal fluids (FeSSIF) were introduced by Prof. Jennifer Dressman in 1998 (1) and contain the natural solubilizers bile salt and lecithin in amounts similar to intestinal fluids. Since their introduction, numerous articles have correlated the in vitro dissolution behavior of poorly water-soluble drugs in biorelevant media to in vivo oral absorption (for recent reviews of IVIVR, see 2, 3). Biorelevant media are also of interest to anticipate potential food effects and to model drug-absorption processes (4). Conventional dissolution media for poorly soluble drugs contain synthetic surfactants, such as sodium dodecyl sulfate, which form micelles. In contrast, FeSSIF and FaSSIF contain natural surfactants that form more complex lipid aggregates. Methods of preparing biorelevant media involve emulsification in a chlorinated solvent (5) or sequential additions (6). Regardless of the method used, for reproducibility, the quality and specification of the taurocholate and lecithin must be taken into account (7). Recently, modified compositions for FeSSIF and FaSSIF have been proposed (8). Phares introduced SIF Powder (www.ePhares.com) consisting of high-specification taurocholate and lecithin to facilitate the rapid and standardized preparation of either FaSSIF or FeSSIF (9). In a recent publication (10), the performance of FaSSIF prepared by the emulsion method, “instant” FeSSIF and FaSSIF prepared by a solvent elimination method, and commercially available SIF Powder were compared. It was concluded that the powder provides an accurate, reproducible, and efficient way of preparing ready-to-use biorelevant media. This paper characterizes SIF Powder and examines how FeSSIF and FaSSIF media can be reproducibly prepared from the powder. The physical, chemical, and microbiological stability of the media were investigated along with the dissolution of three poorly water-soluble drugs in FaSSIF. The results of the structures observed in both biorelevant media are discussed in the context of the physicochemical characteristics of the lecithin and taurocholate. MATERIALS AND METHODS Ketoconazole was obtained from Piramal Healthcare Limited (Mumbai, India); dipyridamole and phenytoin were from Sigma Aldrich Chemie GmbH (Buchs, Switzerland). All other chemicals conform to at least analytical quality. *Corresponding author. diss-17-03-02.indd 6 8/18/2010 1:41:06 PM dx.doi.org/10.14227/DT170310P6