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 sustained release cisapride oral dosage formulation suitable for once-daily administration comprises a plurality of mini-tablets containing cisapride or a salt thereof with an organic acid and capable of releasing cisapride at different sites along the gastrointestinal tract. The mini-tablets include a proportion of immediate release tablets and a proportion of tablets which release cisapride in response to the pH environment at a given site in the distal regions of the gastrointestinal tract and which include cisapride or a salt thereof embedded in a matrix of hydrophilic polymer, said matrix being coated with a pH dependent polymer, the formulation having a Cmax/Cmin ratio under steady state conditions of 2:1 or less as evidenced by a substantially flat plasma profile in vivo.

Abstract: An oral morphine multiparticulate formulation for once-daily administration to a patient, comprising sustained release particles each having a core containing water soluble morphine and an osmotic agent, the core being coated with a rate-controlling polymer coat comprised of ammonio methacrylate copolymers in an amount sufficient to achieve therapeutically effective plasma levels of morphine over at least 24 hours in the patient.

Abstract: A once-daily naproxen formulation for oral administration having a first portion of the naproxen as a multi-particulate pellet form, each pellet having a core of naproxen or a pharmaceutically acceptable salt thereof in association with an organic acid, the core being surrounded by a multi-layer membrane and optionally a second portion of naproxen formulated to release the drug promptly following oral administration.

Abstract: A diltiazem pellet formulation for oral administration comprises a core of diltiazem or a pharmaceutically acceptable salt thereof in association with an organic acid, and a multi-layer membrane surrounding the core and containing a major proportion of a pharmaceutically acceptable film-forming, water insoluble synthetic polymer and a minor proportion of a pharmaceutically acceptable film-forming, water soluble synthetic polymer. The number of layers in the membrane and the ratio of the water soluble to water insoluble polymer being effective to permit release of the diltiazem from the pellet at a rate allowing controlled absorption thereof over a twenty four hour period following oral administration.

Abstract: Pharmaceutical formulations comprise a mono- or di-aminopyridine active agent for administration on a once- or twice-daily basis for use in the treatment of neurological diseases, in particular multiple sclerosis and Alzheimer's disease. The formulations, which are suitable for oral or percutaneous administration of the active agent, include the active agent in a carrier effective to permit release of the mono- or di-aminopyridine at a rate allowing controlled absorption thereof over, on the average, not less than a 12 hour period and at a rate sufficient to achieve therapeutically effective blood levels over a period of 12-24 hours following administration.

Abstract: Pharmaceutical formulations comprise a mono- or di-aminopyridine active agent for administration on a once- or twice-daily basis for use in the treatment of neurological diseases, in particular multiple sclerosis and Alzheimer's disease. The formulations, which are suitable for oral or percutaneous administration of the active agent, include the active agent in a carrier effective to permit release of the mono- or di-aminopyridine at a rate allowing controlled absorption thereof over, on the average, not less than a 12 hour period and at a rate sufficient to achieve therapeutically effective blood levels over a period of 12-24 hours following administration.

Abstract: A transdermal device for the controlled administration of a drug to the skin comprises a reservoir (12) for the drug and an electric circuit which includes an electrode system (13, 14) which is operable to actively transport the drug in a controlled manner from the reservoir (12) towards the skin for transport therethrough, the skin not being part of the electric circuit, and the drug passing through an electrode (13) of said electrode system (13, 14) during the active transport to the skin. The electrode (13) is disposed between the reservoir (12) for the drug and an optional transit chamber (15). The electrode (13) can be permeable to the drug or the electrode can function as a gate, being permeable to the drug in the open condition and less permeable to the drug in the closed condition. The operation of the gate can be determined by the composition or the structure of the electrode (13). The device achieves drug delivery rates comparable to those achieved with iontophoretic devices.

Abstract: Pharmaceutical formulations comprise a mono- or di-aminopyridine active agent for administration on a once- or twice-daily basis for use in the treatment of neurological diseases, in particular multiple sclerosis and Alzheimer's disease. The formulations, which are suitable for oral or percutaneous administration of the active agent, include the active agent in a carrier effective to permit release of the mono- or di-aminopyridine at a rate allowing controlled absorption thereof over, on the average, not less than a 12 hour period and at a rate sufficient to achieve therapeutically effective blood levels over a period of 12-24 hours following administration.

Abstract: A diltiazem pellet formulation for oral administration comprises a core of diltiazem or a pharmaceutically acceptable salt thereof in association with an organic acid, and a multi-layer membrane surrounding the core and containing a major proportion of a pharmaceutically acceptable film-forming, water insoluble synthetic polymer and a minor proportion of a pharmaceutically acceptable film-forming, water soluble synthetic polymer. The number of layers in the membrane and the ratio of the water soluble to water insoluble polymer being effective to permit release of the diltiazem from the pellet at a rate allowing controlled absorption thereof over a twenty four hour period following oral administration.

Abstract: A controlled release powder containing discrete micro-particles for use in edible, pharmaceutical and other controlled release compositions is disclosed. The micro-particles have an average size in the range of from 0.1 to 125 .mu.m. Each of the micro-particles is in the form of a micromatrix of an active ingredient uniformly distributed in at least one non-toxic polymer. The micro-particles have a predetermined release of active ingredient when the dissolution rate thereof is measured according to the Paddle Method of U.S. Pharmacopoeia XX at 37.degree. C. and 75 r.p.m.

Abstract: A diltiazem pellet formulation for oral administration comprises a core of diltiazem or a pharmaceutically acceptable salt thereof in association with an organic acid, and a multi-layer membrane surrounding the core and containing a major proportion of a pharmaceutically acceptable film-forming, water insoluble synthetic polymer and a minor proportion of a pharmaceutically acceptable film-forming, water soluble synthetic polymer. The number of layers in the membrane and the ratio of the water soluble to water insoluble polymer being effective to permit release of diltiazem from the pellet at a rate allowing controlled absorption thereof over a twelve hour period following oral administration. The pellet has a dissolution rate in vitro which when measured in a dissolution apparatus (Paddle) according to U.S. Pharmacopoeia XXI in 0.05 M KC1 at pH 7.0 results in not more than 35% of the total diltiazem being released after 2 hours of measurement.

Abstract: A cap assembly for an enteral feeding container having an inner and outer cap. The inner cap has an upper end forming a tray with an inner peripheral lip and an outer peripheral lip, A flexible inner membrane covers the inner side of the tray of the inner cap to form a seal between the neck of the container and the tray. An outer membrane is placed over the outer side of the tray to form a sealed chamber, A cavity containing an appropriate disinfectant is centrally formed in the tray for receiving an enteral feeding tube spike when the outer membrane is removed, Access to the cavity is achieved by first removing the outer cap, then stripping away the outer membrane.

Abstract: A preparation for the once-daily, percutaneous administration of nicotine comprises nicotine uniformly distributed in a solid, semi-solid or mucilaginous medium which can be placed in intimate contact with the skin, the solid, semi-solid or mucilaginous medium is formed by adding a given amount of nicotine to a solution of a solidifying or gel-forming agent or mixture thereof in a suitable solvent or mixture of solvents and mixing or heating the mixture thereby obtained so as to form the solid, semi-solid or mucilaginous medium. The preparation can be used in a method of treating withdrawal symptoms associated with smoking cessation and for combating the psychological dependence that occurs through frequent smoking.

Abstract: A diltiazem pellet formulation for oral administration comprises a core of diltiazem or a pharmaceutically acceptable salt thereof in association with an organic acid, and a multi-layer membrane surrounding the core and containing a major proportion of a pharmaceutically acceptable film-forming, water insoluble synthetic polymer and a minor proportion of a pharmaceutically acceptable film-forming, water soluble synthetic polymer. The number of layers in the membrane and the ratio of the water soluble to water insoluble polymer being effective to permit release of diltiazem from the pellet at a rate allowing controlled absorption thereof over a twelve hour period following oral administration. The pellet has a dissolution rate in vitro which when measured in a dissolution apparatus (Paddle) according to U.S. Pharmacopoeia XXI in 0.05 M KCl at pH 7.0 results in not more than 35% of the total diltiazem being released after 2 hours of measurement.

Abstract: A non-aqueous pharmaceutical liquid suspension having improved bioavailability for oral administration comprises an active ingredient suspended in an edible, non-aqueous carrier vehicle such as an oil, wherein the active ingredient is in the form of controlled release particles containing the active ingredient and optionally an excipient in intimate admixture with at least one non-toxic polymer, the particles being coated with, distributed through or adsorbed onto said polymer, and the particles further having an average size in the range 0.1 to 150 microns and a predetermined release of active ingredient.

Abstract: A transdermal device having a detachably mounted electrode with a first surface adapted for contact with human skin and through which a drug substance contained in the electrode passes to the skin under the influence of an iontophoretic or electro-osmotic force and a second surface which is electrically conducting, the electrode has a surface area in contact with the skin, in use, in the range 0.1 to 30 cm.sup.2 and a drug dissolved or dispersed in a hydrophilic medium at a concentration in the range 0.1 to 15% (w/v) based on the hydrophilic medium.

Abstract: A method of using nicotine in the treatment of various conditions susceptible to alleviation by nicotine therapy such as disease states characterized by reduced central cholinergic function. Nicotine is administered to a subject initially having a blood supply substantially free of nicotine at a dose and for a period sufficient to allow the subject to tolerate the dose and thereafter increasing the dose of nicotine at intervals until a therapeutic dose is achieved. Smokers may also benefit from the treatment regimen.

Abstract: A controlled absorption diltiazem pellet formulation for oral administration comprises a core of diltiazem or a pharmaceutically acceptable salt thereof in association with an organic acid, and a multi-layer membrane surrounding the core and containing a major proportion of a pharmaceutically acceptable film-forming water insoluble synthetic polymer and optionally a minor proportion of a pharmaceutically acceptable film-forming, water soluble synthetic polymer. The number of layers in the membrane and the ratio of the water soluble to water insoluble polymer, when said water soluble polymer is present, being effective to permit release of diltiazem from the pellet at a rate allowing controlled absorption thereof over not less than a twelve hour period following oral administration. The pellet has a dissolution rate in vitro which when measured in a dissolution apparatus (paddle) according to U.S. Pharmacopoeia XXI in 0.05 M KCl at pH 7.

Abstract: A controlled release formulation comprising an adsorbate of a mixture of a pharmaceutically useful active ingredient and an inactive substance adsorbed on a cross-linked polymer. The inactive substance is selected to modify the dissolution of the active ingredient from the cross-linked polymer in vivo.