Abstract: The present invention includes controlled release dosage forms and methods of designing and manufacturing dosage forms to obtain specific release profiles, for example, zero-order release profiles, escalating release profiles or decreasing release profiles. The dosage forms of the present invention can include spatial variation of API concentration in the dosage form and can include nested regions. Dosage forms according to the present invention may be manufactured by any appropriate method for obtaining the internal structure as disclosed herein for producing zero-order release profiles and increasing or decreasing release profiles. The invention further includes methods of manufacturing such dosage forms, such as by three-dimensional printing, possibly also including compression of the dosage form after three-dimensional printing. The invention further includes methods of designing such dosage forms.

Abstract: A new mold solves problems that arise from differential changes in geometry inherent to casting metal in a ceramic mold, by control of the internal morphology between the surfaces of the mold that face the casting, and that face the external environment. Layered fabrication techniques are used to create a ceramic mold. For example, an internal geometry composed of a cellular arrangement of voids may be created within the mold wall. Structures may be designed and fabricated so that the ceramic mold fails at an appropriate time during the solidification and/or cooling of the casting. Thus, the casting itself is not damaged. The mold fails to avoid rupture, or even distortion, of the casting. A thin shell of ceramic defines the casting cavity. This shell must be thin enough to fail due to the stresses induced (primarily compressive) by the metal next to it and partly adherent to it.

Abstract: The present invention relates to high-throughput systems and methods to prepare a large number of component combinations, at varying concentrations and identities, at the same time, and high-throughput methods to test tissue barrier transfer, such as transdermal transfer, of components in each combination. The methods of the present invention allow determination of the effects of inactive components, such as solvents, excipients, enhancers, adhesives and additives, on tissue barrier transfer of active components, such as pharmaceuticals. The invention thus encompasses the high-throughput testing of pharmaceutical compositions or formulations in order to determine the overall optimal composition or formulation for improved tissue transport, such as transdermal transport.

Abstract: The invention concerns arrays of solid-forms of substances, such as compounds and rapid-screening methods therefor to identify solid-forms, particularly of pharmaceuticals, with enhanced properties. Such properties include improved bioavailability, solubility, stability, delivery, and processing and manufacturing characteristics. The invention relates to a practical and cost-effective method to rapidly screen hundreds to thousands of samples in parallel. The invention further provides methods for determining the conditions and/or ranges of conditions required to produce crystals with desired compositions, particle sizes, habits, or polymorphic forms. In a further aspect, the invention provides high-throughput methods to identify sets of conditions and/or combinations of components compatible with particular solid-forms, for example, conditions and/or components that are compatible with advantageous polymorphs of a particular pharmaceutical.

Abstract: A uniaxially compressed dosage form manufactured by three-dimensional printing that preserves the predetermined internal architecture of the dosage form while producing an improved surface finish. The compression compacts the dosage form, eliminating at least some of the void space that remains at the end of conventional three-dimensional printing. Surface finish obtained as a result of the uniaxial compression process can be essentially equal to that obtained from conventional tablet pressing. Additionally, the internal structure or spatial variation of composition of the dosage form is preserved during the pressing operation, with geometric shrinkage occurring mostly in the direction of the axis of pressing. Further, as a result of compression, a greater quantity of API can be packed into a given final volume of dosage form.

Abstract: Systems and methods are described that allow the high-throughput preparation, processing, and study of arrays of samples, each of which comprises at least one compound. Particular embodiments of the invention allow a large number of experiments to be performed in parallel on samples that comprised of one or more compounds on the milligram or microgram quantities of compounds. Other embodiments of the invention encompass methods and devices for the rapid screening of the results of such experiments, as well as methods and devices for rapidly determining whether or not similarities exist among groups of samples in an array. Particular embodiments of the invention encompass methods and devices for the high-throughput preparation of different forms of compounds (e.g., different crystalline forms), for the discovery of new forms of old compounds, and for the discovery of new methods of producing such forms.

Abstract: A powder bed (32) is built up by repeated deposition of a slurry that contains powder. Layers are made by depositing a liquid dispersion of the desired powdered material, which then slip-casts into the forming powder bed to make a new layer (34). The slurry may be deposited in any suitable manner, such as by raster or vector scanning, or by a plurality of simultaneous jets that coalesce before the liquid slip-casts into the bed, or by individual drops, the deposits of which are individually controlled, thereby generating a regular surface for each layer.

Abstract: A device for controlling or altering the temperature of a liquid at the point of dispensing. A temperature-altering device is thermally coupled to a dispensing device to compensate for heat dissipated into the liquid as it passes through the dispensing device during dispensing. The dispensing device may be for example, a miniature solenoid valve (microvalve), a piezoelectric printhead, or the like. According to aspects of the invention, a temperature-altering device provides or reduces heat at the point of dispensing in order to alter, control or maintain a constant temperature of the dispensed liquid. As a result, improvement is obtained in the consistency of the fluid regime of the dispensed droplet stream. The temperature-altering device may be a thermoelectric device capable of moving heat either from or to the dispensing structure, or may be a heater.

Abstract: A method of producing an oriented oxide superconducting film. A metal oxyfluoride film is provided on a substrate. The metal oxyfluoride film comprises the constituent metallic elements of an oxide superconductor in substantially stoichiometric proportions. The film is then converted into the oxide superconductor in a processing gas having a total pressure less than atmospheric pressure.

Abstract: Systems and methods are described that allow the high-throughput preparation, processing, and study of arrays of samples, each of which comprises at least one compound. Particular embodiments of the invention allow a large number of experiments to be performed in parallel on samples that comprised of one or more compounds on the milligram or microgram quantities of compounds. Other embodiments of the invention encompass methods and devices for the rapid screening of the results of such experiments, as well as methods and devices for rapidly determining whether or not similarities exist among groups of samples in an array. Particular embodiments of the invention encompass methods and devices for the high-throughput preparation of different forms of compounds (e.g., different crystalline forms), for the discovery of new forms of old compounds, and for the discovery of new methods of producing such forms.

Abstract: Systems and methods are described that allow the high-throughput preparation, processing, and study of arrays of samples, each of which comprises at least one compound. Particular embodiments of the invention allow a large number of experiments to be performed in parallel on samples that comprised of one or more compounds on the milligram or microgram quantities of compounds. Other embodiments of the invention encompass methods and devices for the rapid screening of the results of such experiments, as well as methods and devices for rapidly determining whether or not similarities exist among groups of samples in an array. Particular embodiments of the invention encompass methods and devices for the high-throughput preparation of different forms of compounds (e.g., different crystalline forms), for the discovery of new forms of old compounds, and for the discovery of new methods of producing such forms.

Abstract: Microchip delivery devices are provided that control both the rate and time of release of molecules. In one embodiment, an implantable microchip device is provided for the controlled delivery of drug molecules into a patient comprising at least one substrate; a plurality of reservoirs in the substrate; a release system which includes drug molecules for release, the release system being provided in each of the reservoirs; a reservoir cap positioned on or in each of the reservoirs over the release system, the reservoir cap comprising a material that undergoes a phase change in response to a change in temperature; and a heating means capable of selectively causing the phase change independently in each reservoir cap, to release the molecules from the reservoirs. The reservoirs can contain multiple drugs or other molecules in variable dosages. Each of the reservoirs of a single microchip can contain different molecules and/or different amounts and concentrations, which can be released independently.

Abstract: The invention includes dispensing a suspension containing solid particles for use in manufacturing a dosage form or other biomedical article by 3DP. The suspension contains solid particles suspended in a liquid. The solid particles may be one or more Active Pharmaceutical Ingredients. The solid particles may be particles of material that are insoluble in the liquid, or they may be particles of a substance that have already dissolved in the liquid up to the saturation level and are present in a concentration beyond what can be dissolved. In addition to solid particles, the liquid may also contain other substances dissolved in it, either substances containing Active Pharmaceutical Ingredients (API) or substances without API. One aspect of the invention includes prevention of agglomeration by adding one or more of several categories of additives to the suspending liquid.

Abstract: Micron scale dielectric items are manipulated by methods and apparatus taking advantage of spatially non-uniform field. Such fields give rise to a force on dielectric items, directing them generally toward regions of more concentrated field. The electrode may be elongated, either unitary, with a generally planar counter electrode, or dual, such as parallel pins, loops or plates. If dual, particles are generally attracted to regions of high field concentration, including tips, edges and spaces between electrode conductors. Items can be granular, threadlike, or sheets, and microelectronic parts and other shapes. Items can also be collected directly into a recess of a pharmaceutical material delivery microchip, with a conductive membrane of the microchip acting as a manipulating electrode. Items are attracted without regard to their surface charge, or the polarity of the field, which can be AC or DC. Charging, or knowing the charge of items to be manipulated is not necessary.

Abstract: The transdermal assay apparatus includes first, second, and third members. The first member has one or more sample surfaces, each of which is configured to receive a sample thereon. The second member defines one or more reservoirs, each of which has an opening on a surface of the second member. Each sample surface is substantially the same size as each opening. The transdermal assay apparatus also includes a magnetic clamp configured to clamp a tissue specimen between the sample surface and the opening. The magnetic clamp preferably includes a magnet having a strength that is selected based on the clamping force required between the first member and the second member. The invention also provides a method for using a transdermal assay apparatus.

Abstract: Apparatus and methods are provided for the delivery of molecules to a site via a carrier fluid. The apparatus include microchip devices which have reservoirs containing the molecules for release. The apparatus and methods provide for active or passive controlled release of the molecules. Embodiments include systems for release of fragrance molecules and beverage additives.

Abstract: Solid free-form (SSF) techniques for making medical devices for implantation and growth of cells from polymers or polymer/inorganic composites using computer aided design are described. Examples of SFF methods include stereo-lithography (SLA), selective laser sintering (SLS), ballistic particle manufacturing (BPM), fusion deposition modeling (FDM), and three dimensional printing (3DP). The devices can incorporate inorganic particles to improve the strength of the walls forming the pores within the matrix and to provide a source of mineral for the regenerating tissue. The devices can contain tissue adhesion peptides, or can be coated with materials which reduce tissue adhesion. The macrostructure and porosity of the device can be manipulated by controlling printing parameters. Most importantly, these features can be designed and tailored using computer assisted design (CAD) for individual patients to optimize therapy.

Abstract: Microchip delivery devices are provided that control both the rate and time of release of molecules, wherein the device includes a substrate, at least one reservoir in the substrate containing the molecules, and a reservoir cap positioned on the reservoir over the molecules, wherein the molecules are released from the reservoir upon heating or cooling the device or a portion thereof sufficient to rupture the reservoir cap. In a preferred embodiment, the device includes a resistor integrated into the reservoir or mounted near the reservoir, which upon application of an electric current through the resistor, causes at least one of the contents of the reservoir to thermally expand, vaporize, phase change, or undergo a thermally driven reaction, such that the reservoir cap ruptures due to mechanical stress.

Abstract: Dosage forms prepared by solid free form fabrication (SFF) provide release of medicament in multiple phases.

Abstract: Apparati and methods are provided for the delivery of molecules to a site via a carrier fluid. The apparati include microchip devices which have reservoirs containing the molecules for release. The apparati and methods provide for active or passive controlled release of the molecules. Preferred embodiments include systems for intravenous administration of drugs, wherein drug molecules are released from the microchip devices into a carrier fluid ex vivo, such as a saline solution, forming a drug/saline solution mixture which is then delivered to a patient intravenously.