Dissolution behavior of various drugs in different FaSSIF versions.

Biorelevant media have proven to be useful in predicting the performance of poorly soluble drugs in the gastrointestinal tract. Several versions of fasted state simulated intestinal fluids have been published and compared with respect to their physical chemical properties and solubilization of drugs. However, to date there have been no reports in the literature comparing dissolution of poorly soluble drugs in these media.

Advances in the design of fasted state simulating intestinal fluids: FaSSIF-V3.

Biorelevant media are commonly used to simulate the physiological composition of human intestinal fluids (HIF) in in vitro solubility and dissolution investigations. In comparison with the surfactant solutions or blank buffers, these media are able to better reflect the physiological solubility and dissolution behavior of poorly soluble active pharmaceutical ingredients (APIs). The aim of this investigation was to review the composition of FaSSIF and FaSSIF-V2 according to recently summarized data about the physiological composition of fasted state human intestinal fluid and propose an updated version, FaSSIF-V3.

The apparent solubilizing capacity of simulated intestinal fluids for poorly water-soluble drugs.

Drug solubility testing in biorelevant media has become an indispensable tool in pharmaceutical development. Despite this importance, there is still an incomplete understanding of how poorly soluble compounds interact with these media. The aim of this study was to apply the concept of the apparent solubilization capacity to fasted and fed state simulated intestinal fluid (FaSSIF and FeSSIF, respectively).

Instant solubilization of poorly water-soluble drugs by in-situ loading of aqueous phospholipid dispersions suitable for parenteral administration.

The features of a new, in situ method for solubilizing poorly soluble drugs (SupraVail Instant Solubilization) are demonstrated. The resulting formulations are suitable for parenteral administration in preclinical and clinical studies. The technique avoids drug precipitation upon dilution and circumvents the need for co-administration of high organic solvent concentrations.

Absorption of poorly water soluble drugs subject to apical efflux using phospholipids as solubilizers in the Caco-2 cell model.

The purpose of this work was to determine the influence of liposomal solubilization of poorly water soluble drugs exhibiting apical efflux on permeation kinetics and cell toxicity in Caco-2 cells. The HIV-protease inhibitors indinavir and saquinavir were incorporated in phosphatidylcholine liposomes at maximal drug-to-lipid mass ratios and their absorption was determined in Caco-2 cell cultures grown on Transwell inserts using purely aqueous drug solutions as reference. A novel mathematical model was developed to quantitatively delineate the contribution of passive membrane permeation and carrier mediated efflux to transport across the cell monolayer and passive permeability coefficient and maximal efflux rate and affinity constant of the transporter system were determined.

Lipophilic drug transfer between liposomal and biological membranes: what does it mean for parenteral and oral drug delivery?

This review presents the current knowledge on the interaction of lipophilic, poorly water soluble drugs with liposomal and biological membranes. The center of attention will be on drugs having the potential to dissolve in a lipid membrane without perturbing them too much. The degree of interaction is described as solubility of a drug in phospholipid membranes and the kinetics of transfer of a lipophilic drug between membranes.

Characteristics of a novel phospholipid-based depot injectable technology for poorly water-soluble drugs.

Phospholipid concentrates in a water miscible solvent were explored as injectable formulations for the poorly water-soluble drugs, using the anti-infective PHA 244 as model substance. Formulations containing up to 70% w/v phospholipid could dissolve 15% PHA 244. The formulations showed excellent syringe-ability and no precipitation of the drug after dilution in an excess of water.