Pion Inc.

F. Hoffmann-la Roche Ag

Alex Avdeef

Per E Nielsen

Manfred Kansy

Deren J Dohoda

Konstantin L Tsinman

Dmytro Voloboy

Michael J DeMaria

Chau M Du

The invention provides a permeation device () comprising a receiving vessel () having an aperture adapted for receiving an insert well (). Both the vessel () and well () are used as either donor or acceptor compartments for permeability assays. The vessel () or well () comprises a porous suppor ()t, which may comprise biological or biomimetic materials, adapted for a molecular entity to permeate therethrough. In one embodiment, a stirring member () disposed in the vessel () can provide solution agitation to reduce aqueous boundary layer thickness adjacent to the support (). Boundary layer thicknesses can be reduced by a device () of the invention to less than about 15 um such that a molecular entity permeating the support closely approximates in vivo absorption and transport conditions.

Permeation device and method for reducing aqueous boundary layer thicknesses

The invention deals with a method for the assessment of the effect of excipients, pH and combinations thereof on the predicted absorption properties of low solubility compounds, comprising the step of assessing a change in a flux function for a combination of a low solubility compound and an excipient at at least one predefined pH value. The method allows a fast, accurate, and economic evaluation of an excipient being capable of optimizing the absorption of drug molecules, i.e. low solubility compounds. Furthermore, animal experiments can be excluded and use of compounds can be reduced in such evaluation. Thus, screening for future formulation efficacy (pH and excipient effects on solubility and permeability) of drug candidates can be justified, since the method is fast, compound-sparing, cost-effective, and reasonably accurate.

Method for assessing absorption properties of low solubility compounds

An apparatus for evaluating physicochemical properties of sample materials contained in an array of vessels includes: a light detector; a light source for transmitting a light beam through the sample material in a vessel to the light detector; an analyzer for processing data from the light detector to determine concentration-related properties of the sample material as a function of time; and a mixing system. The mixing system includes: a plurality of magnetic stirrer elements, each for being placed in a sample material in a different one of the array of vessels; an array of magnetic drive elements, each associated with a different one of the array of vessels and being magnetically coupled with a magnetic stirrer element in an associated vessel; and a drive mechanism coupled to the array of magnetic drive elements for simultaneously moving each of the magnetic drive elements relative to an associated vessel.

Methods and systems for in situ physicochemical property testing

This invention improves the PAMPA (parallel artificial membrane permeability assay) method used in pharmaceutical, biotechnological, and agrochemical R&D. This new high-throughput method and apparatus for measurement of permeability and membrane retention of compounds overcomes shortcomings of prior art and includes sensitivity and speed enhancing reagents. The phospholipid membranes used here consist of 10&#x2013;74% wt/vol soybean lecithin extract dissolved in dodecane. Concentrations are measured by direct UV spectroscopy. To reduce membrane retention, surfactants, cyclodextrins, or water-soluble lipophilic polymers with low UV absorption are used in the acceptor comparment of the permeation cells and create an artificial sink state. A pH gradient established between donor and acceptor solutions creates a secondary sink state. This 'double-sink' makes successful modeling of passive-diffusion transport of molecules possible. By accelerating transport of certain molecules, it shortens measurement time and increases assay throughput. A new permeability equation accounts for the 'double-sink' condition as well as membrane retention.

Method and apparatus for improving in vitro measurement of membrane permeability of chemical compounds

This invention relates to a method for the determination of solubility of a compound and an analytical device for carrying out said method. The basic method involves determining solubility of a compound by measuring the UV spectrum of a reference solution of the compound, under conditions avoiding or suppressing precipitation, and comparing it to the UV spectrum of a saturated sample solution of the compound. Variations of the basic method include: (a) making reference solutions either by dilution of the sample solution to the point where precipitation is avoided, or making reference solutions by adding a water-miscible cosolvent to the sample solution so that precipitation is suppressed, and comparing the UV absorbances of the compound under reference conditions to the compound in a saturated solution, (b) determining the true aqueous solubility from the effect on the pK that results from dissolving the compound in an aqueous solution containing some DMSO (typically 0.1-5% v/v), and (c) correcting concentrations determined from the UV absorbance values for impurities and other factors that might affect the shape of the sample absorbance curve taken of the saturated solution.

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Reading, MA, United States of America

Alex Avdeef