Abstract: A taste-masked micromatrix powder in which the ratio of a cationic copolymer synthesized form dimethylaminoethyl methacrylate and neutral methacrylic acid esters compared to a drug having poor organoleptic properties is greater than 2 to 1, preferably 4 to 1, most preferably 6 to 1 (wt/wt). Taste masked immediate release micromatrix powders can be formed by spray drying the drug and cationic copolymer whereas sustained release micromatrix powders can be formed by granulating controlled release powders, which can be made by spray drying the drug with a retarding polymer, with the cationic copolymer. The immediate release or sustained release taste-masked powders of this invention can be incorporated into conventional oral dosage forms such as sprinkles, suspension, fast melt tablets, chewable tablets or effervescent tablets.

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 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: A syringe (10) comprises a barrel (11) containing an internal cylindrical body (12) containing a liquid (14) and communicating with a delivery needle (15). The needle (15) is covered before use by a removable sheath (16), and after the sheath (16) is removed, the needle (15) is concealed by a displaceable sleeve (20). In use the sleeve (20) is pressed against the skin by applying pressure while holding the barrel (11). The sleeve (20) is thereby retracted into the barrel (11) allowing the needle (15) to penetrate the skin. The movement of the sleeve (20) also activates a gas generator (17) which expels the liquid (14) from the needle (15). When delivery is complete and the syringe (10) is taken from the skin, a coil spring (22) moves the sleeve (20) back to the starting position again concealing the needle (15). The coil spring (22) is torsionally biased before use and causes a rotational movement of the sleeve (20) relative to the barrel (11) when the sleeve (20) moves into and out of the barrel (11).

Abstract: An improved electrode and iontophoretic device and method where the electrode exhibits varied resistance. The electrode is made of a conductive material and applied to a flexible substrate. The variation in resistance can be achieved by varying the thickness of the electrode across its length or by varying the conductivity of the material across the area of the electrode or a combination of both. A pair of such electrodes may be used with a power source in electrical relation thereto and applied over a layer of agent to the skin to deliver the agent into the skin iontophoretically. The pair of electrodes may be shaped so as to cover a portion of the face, hands, feet or other body parts to iontophoretically apply particular agents to those areas.

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: An improved drug delivery kit and method of packaging the same. The method includes providing a tray having first and second recesses for receiving a drug delivery device and drug cartridge respectively, and an opening in the tray within the second recess, placing the drug delivery device in the first recess, covering the tray with a sealable material, sealing the material to the tray so as to create a seal around the first and second recesses, so as to isolate the first recess from the second recess, sterilising the tray, and inserting the drug cartridge through the opening and into second recess. The opening is sized such that insertion of the drug cartridge through the opening and into the second recess elastically stresses the tray and removal of the drug cartridge from the opening irreversibly deforms the tray, thereby creating a tamper-proof drug delivery kit.

Abstract: An intradermal drug delivery device comprises a housing (301a, 301b) having a drug reservoir (312) therewithin and a gas generation chamber (313) separated from the reservoir (312) by a displaceable membrane (311). A microprocessor-controlled electrolytic cell (316a, 316b, 319) provides gas to expand the gas generation chamber (313) and thereby contract the reservoir (312). A hollow needle (310), communicating at an inner end thereof with the reservoir (312), extends from a lower surface (308) of the housing (301) such that contraction of the reservoir (312) forces drug to escape therefrom via the needle (310). The device permits delivery of drugs of relatively large molecular weights at slow controllable rates. A displaceable protective cover (303) is mounted in means (307) allowing movement of the cover (303) between extended and retracted positions (305, 306). The cover (303) has an adhesive lower surface (309) for attachment to the skin of a subject.

Abstract: Oral drug delivery device having a housing with walls of water permeable material and having at least two chambers separated by a displaceable membrane. The first chamber receives drug and has an orifice through which the drug is expelled under pressure. The second chamber contains at least one of two spaced apart electrodes forming part of an electric circuit which is closed by the ingress of an aqueous ionic solution into the second chamber. When current flows through the circuit, gas is generated and acts on the displaceable membrane to compress the first chamber and expel the active ingredient through the orifice for progressive delivery to the gastrointestinal tract.

Abstract: A controlled release pharmaceutical formulation comprises nanoparticles formed of a biodegradable polycyanoacrylate polymer in which insulin is entrapped, the insulin being complexed to the polycyanoacrylate. These particles are capable of releasing bioactive insulin in vivo at a slower release rate than nanoparticles in which the insulin is free. The formulation may comprise a mixture of nanoparticles in which the insulin is free and nanoparticles in which it is complexed, so as to obtain the desired release profile. The nanoparticles have a preferred loading of 15-25% w/v insulin and a preferred size of 100-400 nm. Administration may be oral or parenteral, and for oral administration, an enteric coating may be provided to target release to the small intestine. Complexing of the insulin is achieved by the polymerisation of cyanoacrylate monomer in the presence of insulin at a low pH, preferably at about pH=2.

Abstract: A controlled release pharmaceutical formulation which comprises cyclosporin entrapped in a biodegradable polymer to form microspheres or nanospheres such that the cyclosporin is substantially in an amorphous state and the biodegradable polymer comprises greater than 12.5% w/w poly(lactide). The biodegradable polymer is suitably poly-D,L-lactide or a blend of poly-D,L-lactide and poly-D,L-lactide-co-glycolide. Additionally, an enteric coating can be applied to the microspheres or nanospheres or to the oral dosage form incorporating the microspheres or nanospheres to protect the formulation while it passes through the stomach. A particularly suitable formulation comprises 50% w/w cyclosporin-loaded 80:20 blend of poly-D,L-lactide-co-glycolide to poly-D,L-lactide micro- and/or nanospheres. This formulation has the combined properties of nearly complete but relatively slow release of cyclosporin within 8 hours and is useful for targeting cyclosporin to the small intestine when administered orally.

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: An improved controlled release tablet formulation for the release of potassium chloride through a differentially permeable membrane from which the release of potassium chloride can be accurately controlled to minimize the likelihood of producing high localized concentrations of potassium within the gastrointestinal tract.

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.