Abstract: The present disclosure relates generally to crosslinked cation-binding polymers comprising monomers containing carboxylic acid groups, wherein the polymer contains calcium and/or magnesium cations that are counterions to about 15% to about 35% of the carboxylic acid groups in the polymer. The present disclosure also relates to methods of preparation of the polymers, and compositions, formulations, and dosage forms containing the polymers, and methods of using the polymers, compositions, formulations, and/or dosage forms to treat various diseases or disorders, including those involving ion and/or fluid imbalances.

Abstract: A secondary compound library produced by a method of screening a compound library or portion thereof by absorption is provided. The method includes a step (i) that screens a primary compound library or portion thereof having a plurality of test samples containing isolated compounds or isolated mixtures of compounds per test sample by generating an in vivo absorption profile for each of the test samples from initial dose data and from in vitro bioavailability data comprising permeability and solubility data for each of the test samples, wherein the absorption profile includes at least one of rate of absorption, extent of absorption, and concentration of a test sample. Step (ii) produces a secondary compound library that includes at least one compound from the primary compound library having a desired absorption profile.

Abstract: Permeability models and methods for creating the models are disclosed. The models include receiving as an input in vitro permeability and structure data for a particular compound. Then the data is mapped to at least one permeability. In some models the data is mapped to a plurality of permeabilities, each associated with a specific region in a mammalian GI tract. Some models may take into consideration solubility, permeability and at least one molecular descriptor associated with the compound of interest.

Abstract: A system for simulating metabolism of a compound in a mammal is disclosed that includes a metabolism simulation model of a mammalian liver. This model has equations which, when executed on a computer, calculate the rate of metabolism of the compound in the cells of the mammalian liver and a rate of transport of the compound into the cells, wherein the simulation model determines an amount of the metabolism product. The rate of metabolism may be a rate of depletion of the compound. The metabolism product may be an amount of the compound remaining after the compound's first passage through the mammalian liver (This is not necessarily limited to first pass, nor would it need to be limited to the liver. Intestinal metabolism could also be modeled). The rate of metabolism may alternatively be a rate of accumulation of a metabolite of the compound.

Abstract: The present invention relates to a pharmacokinetic-based design and selection tool (PK tool) and methods for predicting absorption of an administered compound of interest. The methods utilize the tool, and optionally a separately operable component or subsystem thereof. The PK tool includes as computer-readable components: (1) input/output system; (2) physiologic-based simulation model of one or more segments of a mammalian system of interest having one or more physiological barriers to absorption that is based on the selected route of administration; and (3) simulation engine having a differential equation solver. The invention also provides methods for optimizing as well as enabling minimal input requirements a physiologic-based simulation model for predicting in vivo absorption, and optionally one or more additional properties, from either in vitro or in vivo data.

Abstract: The present invention relates to a pharmacokinetic-based design and selection tool (PK tool) and methods for predicting absorption of an administered compound of interest. The methods utilize the tool, and optionally a separately operable component or subsystem thereof. The PK tool includes as computer-readable components: (1) input/output system; (2) physiologic-based simulation model of one or more segments of a mammalian system of interest having one or more physiological barriers to absorption that is based on the selected route of administration; and (3) simulation engine having a differential equation solver: The invention also provides methods for optimizing as well as enabling minimal input requirements a physiologic-based simulation model for predicting in vivo absorption, and optionally one or more additional properties, from either in vitro or in vivo data.

Abstract: A secondary compound library produced by a method of screening a compound library or portion thereof by absorption is provided. The method includes a step (i) that screens a primary compound library or portion thereof having a plurality of test samples containing isolated compounds or isolated mixtures of compounds per test sample by generating an in vivo absorption profile for each of the test samples from initial dose data and from in vitro bioavailability data comprising permeability and solubility data for each of the test samples, wherein the absorption profile includes at least one of rate of absorption, extent of absorption, and concentration of a test sample. Step (ii) produces a secondary compound library that includes at least one compound from the primary compound library having a desired absorption profile.

Abstract: The present invention relates to a pharmacokinetic-based design and selection tool (PK tool) and methods for predicting absorption of an administered compound of interest. The methods utilize the tool, and optionally a separately operable component or subsystem thereof. The PK tool includes as computer-readable components: (1) input/output system; (2) physiologic-based simulation model of one or more segments of a mammalian system of interest having one or more physiological barriers to absorption that is based on the selected route of administration; and (3) simulation engine having a differential equation solver. The invention also provides methods for optimizing as well as enabling minimal input requirements a physiologic-based simulation model for predicting in vivo absorption, and optionally one or more additional properties, from either in vitro or in vivo data.

Abstract: The present invention relates to a pharmacokinetic-based design and selection tool (PK tool) and methods for predicting absorption of an administered compound of interest. The methods utilize the tool, and optionally a separately operable component or subsystem thereof. The PK tool includes as computer-readable components: (1) input/output system; (2) physiologic-based simulation model of one or more segments of a mammalian system of interest having one or more physiological barriers to absorption that is based on the selected route of administration; and (3) simulation engine having a differential equation solver. The invention also provides methods for optimizing as well as enabling minimal input requirements a physiologic-based simulation model for predicting in vivo absorption, and optionally one or more additional properties, from either in vitro or in vivo data.

Abstract: The present invention relates to a pharmacokinetic-based design and selection tool (PK tool) and methods for predicting absorption of an administered compound of interest. The methods utilize the tool, and optionally a separately operable component or subsystem thereof. The PK tool includes as computer-readable components: (1) input/output system; (2) physiologic-based simulation model of one or more segments of a mammalian system of interest having one or more physiological barriers to absorption that is based on the selected route of administration; and (3) simulation engine having a differential equation solver. The invention also provides methods for optimizing as well as enabling minimal input requirements a physiologic-based simulation model for predicting in vivo absorption, and optionally one or more additional properties, from either in vitro or in vivo data.

Abstract: The present invention relates to a pharmacokinetic-based design and selection tool (PK tool) and methods for predicting absorption of an administered compound of interest. The methods utilize the tool, and optionally a separately operable component or subsystem thereof. The PK tool includes as computer-readable components: (1) input/output system; (2) physiologic-based simulation model of one or more segments of a mammalian system of interest having one or more physiological barriers to absorption that is based on the selected route of administration; and (3) simulation engine having a differential equation solver. The invention also provides methods for optimizing as well as enabling minimal input requirements a physiologic-based simulation model for predicting in vivo absorption, and optionally one or more additional properties, from either in vitro or in vivo data.

Abstract: There is disclosed a composition containing a biologically active polypeptide selected from LHRH, an LHRH analog, somatostatin and a somatostatin analog, in a therapeutically effective amount, a membrane permeability enhancing agent, and a protease enzyme inhibitor enveloped within an enteric coating. The composition possesses enhanced bioavailability upon oral administration.

Abstract: A disposable or recyclable device is provided for packaging and transporting ready-to-use viable cell monolayers, particularly confluent cell monolayers. The device includes a liquid impervious housing having a housing base defining an interior filled with fluid medium, a plurality of detachable and spatially separated permeable membrane inserts each having a confluent cell monolayer attached thereon, and a removable lid. The permeable membrane inserts are disposed in an interior of the housing in a spatially addressable array and the housing base is sealed by the lid so as to separate the membrane inserts from an external environment and to exclude excess air from the fluid filled interior. The device optionally includes a disposable or recyclable environmental control system for regulating chemical and/or physical conditions during transport.

Abstract: The invention provides a compact device and simple method for circulating fluid over the surface of a membrane. The device comprises a housing that in combination with the surface of the membrane defines an enclosed volume through which the fluid is circulated. Some embodiments will include a membrane holding layer, a fluid dispersing layer, or both. The membrane holding layer has an opening through it to expose a predetermined surface area of the membrane to the fluid. The dispersing layer has a set of openings, typically slits, through the dispersing layer to disperse fluid over the surface of the membrane. Some embodiments may include electrodes for sensing or applying electrical potential to the membrane. A particularly preferred embodiment comprises a double sided device including a first housing, dispersing layer and membrane holding layer on one side of a membrane and a second housing dispersing layer and membrane holding layer on the other side of the membrane.

Abstract: The invention provides a compact device of simple construction for holding a membrane in contact with a pair of fluids, one on each side of the membrane. According to the invention, the membrane holder comprises a base and an upper cap, with the membrane held between them. Fluids may be circulated over the surfaces of the membrane. Electrode ports are provided through which electrodes may be placed in proximity to the membrane for measuring or applying electrical potential across the membrane. The membrane holder comprises a base, which includes a lower plate and a center plate secured thereto, and an upper cap, which screws into the base by means of a threaded connection between them. The upper cap may be sealed to provide an enclosed volume for holding one of the fluids or the upper cap may be open to provide an open reservoir for holding the fluid. One or more membrane holders according to the invention may be placed in and held by a specially constructed heater stand.

Abstract: An apparatus for determining transport characteristics across membranes and tissue sections comprises a plurality of cell blocks, where each cell block includes a pair of half-cells which hold the membrane or tissure section therebetween. A circulation path is provided in each half-cell block for exposing a fluid to one side of the membrane or tissue section. The cell blocks are maintained linearly within a base unit including a front plate and a back plate. The front and back plates are heated to maintain the cell blocks at a desired temperature.