Abstract: A pharmaceutical composition and an oral dosage form are disclosed comprising an opiate and an irritant. A method is also described for discouraging abuse of an opiate comprising combining a therapeutically effective amount of an opiate and an irritant into an oral dosage form. A method is also described for treating pain by administering a therapeutically effective amount of an opiate and an irritant in an oral dosage form.

Abstract: A method of identifying a peptide which permits or facilitates the transport of an active agent through a human or animal tissue. A predetermined amount of phage from a random phage library or preselected phage library is plated unto or brought into contact with a first side, preferably the apical side, of a tissue sample or polarized tissue cell culture. At a predetermined time, the phage which is transported to a second side of the tissue opposite the first side, preferably the basolateral side, is harvested to select transported phage. This modified phage is amplified in a host. This cycle of events is repeated (using the transported phage produced in the most recent cycle) a predetermined number of times to obtain a selected phage library containing phage which can be transported from the first side to the second side.

Abstract: A small-scale or micro media-mill and a method of milling materials or products, especially pharmaceutical products, use a dispersion containing attrition milling media and the product to be milled. The milling media can be polymeric, formed of polystyrene or cross-linked polystyrene, having a nominal diameter of no greater than 500 microns. Other sizes include 200 microns and 50 microns and a mixture of these sizes. The mill has a relatively small vessel having an opening, an agitator, a coupling and a motor. The agitator can have a rotor and a shaft extending therefrom. The rotor can be cylindrical or have other configurations, and can have tapered end surfaces. The coupling can close the vessel opening, or attaching the coupling to the motor can close the opening. The coupling has an opening through which the rotor shaft extends into the motor. A sealing mechanism, such as a mechanical or lip seals the shaft while permitting the rotor shaft to rotate.

Abstract: A composition for enteral administration having a non-ionic vegetable oil GIT absorption enhancer capable of increasing the enteral absorbability of drugs, especially oral absorbability of hydrophilic and macromolecular drugs. The non-ionic vegetable oil GIT absorption enhancer, particularly Babassu oil or a derivative thereof, is capable of enhancing the uptake of a drug from the gastrointestinal tract so as to allow therapeutically effective amounts of the drug to be transported across the GIT of an animal such as a human without significant toxic side effects.

Abstract: Controlled release oral pharmaceutical preparations are provided which comprise a therapeutically effective amount of tiagabine or a pharmaceutically acceptable salt thereof dispersed in a rate controlling polymeric matrix comprising at least one rate controlling polymer. The preparation can be formulated into oral dosage forms such as tablets or multiparticulates which provide therapeutically effective plasma levels of tiagabine for a period of at least 12 hours, preferably 24 hours or more. The preparation can provide tiagabine mean plasma concentrations equal to or greater than 50% of the maximum plasma concentration for at least 10 hours, preferably 14 hours, most preferably 16 hours or more.

Abstract: A method of identifying a peptide which permits or facilitates the transport of an active agent through a human or animal tissue. A predetermined amount of phage from a random phage library or a preselected phage library is administered in vivo or in situ to a site in an animal, such as into the gastro-intestinal tract. At a predetermined time, the phage which is transported across a tissue barrier is harvested at a harvesting site, such as in portal or systemic blood or brain tissue, which is separated from the site of administration by the tissue barrier to select transported phage. This transported phage is amplified in a host. This cycle of events is repeated (using the transported phage produced in the most recent cycle) a predetermined number of times to obtain a selected phage library containing phage which can be transported from the site of administration to the harvesting site.

Abstract: A needle (10) for the delivery of a liquid to a subject comprises a shaft (11) having an internal surface defining a longitudinally extending internal bore open at one end (15) to receive a liquid supply, the other end (16) being sharpened for penetration of the skin of the subject. A plurality of apertures (18) are provided, each in the form of a cut extending across the external surface of the side of the shaft (11) at a sufficient depth to establish communication with the bore. The external aperture area is approximately three times greater than the internal aperture area, thereby ensuring that the liquid is delivered to a large surface area of tissue to improve absorption and eliminate fluctuations in the delivery rate. The needle (10) can be mass-produced by aligning a batch of shafts alongside one another and running a grinder across the surfaces of the shafts to create the apertures (18) in the entire batch of needles simultaneously.

Abstract: A composition and method for enhancing paracellular transport across cell layers in an animal comprising an antisense oligonucleotide hybridizable with a region of the messenger RNA coding for the protein occludin which, when hybridized to the occludin mRNA, interferes with its translation such that occludin function is disrupted and paracellular permeability is increased across an epithelial cell layer or and endothelial cell layer in an animal.

Abstract: A drug delivery device having a base member defining a skin-contacting surface, a syringe serving as a reservoir for the drug, and means for expelling drug from the syringe. The syringe is connected to the base member such that the longitudinal axis of the syringe is substantially parallel to the skin surface. A delivery needle is in communication with the syringe. The needle has an angled bend which directs the tip of the needle substantially perpendicular to the skin-contacting surface. In use, the tip of the needle is adapted to penetrate the skin of the subject.

Abstract: A device (10) for generating a pulsatile fluid drug flow comprises a housing (11) containing an expandable-contractible chamber (12) having an inlet (14) and an outlet (15), a valve (16) associated with the outlet (15) which is actuated by the expansion and contraction of the chamber (12), and means (13, 23) for biasing the chamber (12) to its contracted state. When the inlet (14) is connected to a pressurised fluid drug supply the chamber (12) is expanded by the drug, and this expansion of the chamber (12) actuates the valve (16) to open, thereby allowing release of the drug from the chamber (12), following which the chamber (12) contracts under the influence of the biasing means (13, 23), this contraction in turn actuating the valve (16) to close thereby allowing the chamber (12) to refill. By this mechanism, a constant supply of liquid, such as from an osmotic or elastomeric drug delivery pump, can be converted to a pulsatile flow, which may provide a more suitable delivery of certain drugs.

Abstract: A drug delivery device having a base member defining a skin-contacting surface, a syringe serving as a reservoir for the drug, and means for expelling drug from the syringe. The syringe is connected to the base member such that the longitudinal axis of the syringe is substantially parallel to the skin surface. A delivery needle is in communication with the syringe. The needle has an angled bend which directs the tip of the needle substantially perpendicular to the skin-contacting surface. In use, the tip of the needle is adapted to penetrate the skin of the subject.

Abstract: A method of calibrating an analyte sensor in vivo, by providing a first predetermined stimulus to the sensor when the sensor is applied to a subject to produce a first sensor signal, measuring the first sensor signal, and determining a calibration function based on the first measured sensor signal resulting from the predetermined stimulus. The calibration function, when applied to further signals received from the sensor, can be used to provide a calibrated output.

Abstract: A needle (10) for the delivery of a liquid to a subject comprises a shaft (11) having an internal surface defining a longitudinally extending internal bore open at one end (15) to receive a liquid supply, the other end (16) being sharpened for penetration of the skin of the subject. A plurality of apertures (18) are provided, each in the form of a cut extending across the external surface of the side of the shaft (11) at a sufficient depth to establish communication with the bore. The external aperture area is approximately three times greater than the internal aperture area, thereby ensuring that the liquid is delivered to a large surface area of tissue to improve absorption and eliminate fluctuations in the delivery rate. The needle (10) can be mass-produced by aligning a batch of shafts alongside one another and running a grinder across the surfaces of the shafts to create the apertures (18) in the entire batch of needles simultaneously.

Abstract: The present invention provides drug delivery compositions in both concentrated and diluted forms for use as vehicles in the administration of various active agents. The drug delivery compositions are primarily designed for use with lipophilic, amphipathic, and sparingly water soluble active agents, preferably drugs. The drug delivery compositions are to be administered to an animal to effect uptake of the active agent. The primary mode of administration is by intravenous, intra-arterial, intrathecal, intraperitoneal, intraocular, intra-articular, intramuscular or subcutaneous injection. The concentrated drug delivery compositions are formulated with a phospholipid component, a component selected from propylene glycol or certain polyethylene glycol compounds, a high HLB surfactant, and the drug component, with water and/or an oil component optional. The concentrated drug delivery compositions can be diluted with an aqueous fluid to form an oil-in-water microemulsion composition.

Abstract: The present invention provides compositions containing corticosteroid compounds as active agents for the treatment of ailments and diseases of the respiratory tract, particularly the lungs, by way of nasal and pulmonary administration. The corticosteroid compounds are present in a dissolved state in the compositions. The compositions can be formulated in a concentrated, essentially non-aqueous form for storage or in a diluted, aqueous-based form for ready delivery. In a preferred embodiment, the corticosteroid composition contains an ethoxylated derivative of vitamin E and/or a polyethylene glycol fatty acid ester as the high-HLB surfactant present in the formulation. The compositions are ideally suited for inhaled delivery with a nebulizer or for nasal delivery.

Abstract: The invention relates to a multiparticulate modified release composition that in operation delivers an active ingredient in a pulsed or bimodal manner. The multiparticulate modified release composition comprises an immediate release component and a modified release component; the immediate release component comprising a first population of active ingredient containing particles and the modified release component compnsimg a second population of active ingredient containing particles coated with a controlled release coating; wherein the combination of the immediate release and modified release components in operation deliver the active ingredient in a pulsed or a bimodal manner. The invention also relates to a solid oral dosage form containing such a multiparticulate modified release composition.

Abstract: A subcutaneous drug delivery device having a housing having an internal reservoir in communication with a drug delivery needle via a fluid path. An expandable chamber disposed adjacent to the reservoir forces drug from the reservoir to the needle when supplied with a gas. A flow regulating chamber, in communication with the fluid path, is capable of volumetric changes in response to temperature and/or pressure changes. An increase in the volume of the flow regulating chamber increases flow resistance to the needle and thereby counteracts the corresponding increase in delivery rate resulting from the expansion of the expandable chamber due to the same volumetric changes in response to temperature and/or pressure. The device also includes an improved filling system that enables the reservoir within the device to be filled with drug from a source without regard to filling position and with a decreased risk of injury from needles.