Abstract: A polymer blend is prepared by dissolving chitosan and a second polymer in an acidic aqueous solution to form an aqueous polymer blend, dehydrating said aqueous polymer blend, and recovering said polymer blend. The second polymer may be selected from the group consisting of polyether glycols including polyethylene glycols; cellulose esters including cellulose acetate; poloxamers; polysaccharides including dextran and guar; polyvinylpyrrolidones; polyvinyl alcohols; and mixtures or copolymers thereof. These polymer blends swell in an acidic environment and deswell in a more neutral or basic environment. This technology is valuable for the dispensing of biologically active material or drugs into a surrounding environment, especially the environment as is found in the gastrointestinal tract.

Abstract: Therapeutic formulations comprising an effective amount of IL-2 or other lymphokine and a biodegradable polymeric carrier having reverse gelation properties and the methods of use thereof for local or both local and systemic control of proliferative cell disorders are disclosed. The formulation can be administered intratumorally/peritumorally and forms an IL-2 containing depot. The IL-2-containing depot provides for continuous, prolonged release of IL-2 sufficient to stimulate the production of cytotoxic T lymphocytes which function both locally and systemically, without causing unacceptable side effects.

Abstract: A composition and method for releasing a bio-active agent or a drug within a biological environment in a controlled manner is disclosed. The composition is a dual phase polymeric agent-delivery composition comprising a continuous biocompatible gel phase, a discontinuous particulate phase comprising defined microparticles and an agent to be delivered. A microparticle containing a bio-active agent is releasably entrained within a biocompatible polymeric gel matrix. The bio-active agent release may be contained in the microparticle phase alone or in both the microparticles and the gel matrix. The release of the agent is prolonged over a period of time, and the delivery may be modulated and/or controlled. In addition, a second agent may be loaded in some of the microparticles and/or the gel matrix.

Abstract: A water soluble, biodegradable ABA- or BAB-type tri-block polymer is disclosed that is made up of a major amount of a hydrophobic A polymer block made of a biodegradable polyester and a minor amount of a hydrophilic polyethylene glycol(PEG) B polymer block, having an overall average molecular weight of between about 2000 and 4990, and that possesses reverse thermal gelation properties. Effective concentrations of the tri-block polymer and a drug may be uniformly contained in an aqueous phase to form a drug delivery composition. At temperatures below the gelation temperature of the tri-block polymer the composition is a liquid and at temperatures at or above the gelation temperature the composition is a gel or semi-solid. The composition may be administered to a warm-blooded animal as a liquid by parenteral, ocular, topical, inhalation, transdermal, vaginal, transurethral, rectal, nasal, oral, pulmonary or aural delivery means and is a gel at body temperature. The composition may also be administered as a gel.

Abstract: A water soluble biodegradable ABA- or BAB-type triblock polymer is disclosed that is made up of a major amount of a hydrophobic polymer made of a poly(lactide-co-glycolide) copolymer or poly(lactide) polymer as the A-blocks and a minor amount of a hydrophilic polyethylene glycol polymer B-block, having an overall weight average molecular weight of between about 2000 and 4990, and that possesses reverse thermal gelation properties. Effective concentrations of the triblock polymer and a drug may be uniformly contained in an aqueous phase to form a drug delivery composition. At temperatures below the gelation temperature of the triblock polymer the composition is a liquid and at temperatures at or above the gelation temperature the composition is a gel or semi-solid. The composition may be administered to a warm-blooded animal as a liquid by parenteral, ocular, topical, inhalation, transdermal, vaginal, transurethral, rectal, nasal, oral, pulmonary or aural delivery means and is a gel at body temperature.

Abstract: The method for automatic dosing of drugs utilizes a microdelivery device which may be implanted in or otherwise administered to an animal or human. A microdelivery device is configured to have at least one compartment containing at least one drug so that a plurality of doses of the drug(s) are held within the device. In accordance with the present invention, the microdelivery device selectively actuates a compartment to selectively release doses of the drug(s) to provide an efficacious dosing pattern. One primary function of the present invention is to release two or more pesticides in such a pattern that parasites are effectively controlled while preventing the development of tolerance to the drugs within the parasites. Preferably, the microdelivery device is programmable to effectuate the release of the drug(s) at a desired time to maintain efficacious levels of the drug while minimizing the amount of drug which must be used.

Abstract: The apparatus for automatic administration and dosing of one or more drugs comprises a microdelivery device which may be implanted in or otherwise administered to an animal or human. The microdelivery device is configured to have at least one compartment containing at least one drug so that a plurality of doses of the drug(s) are held within the device. In accordance with the present invention, the microdelivery device selectively actuates a compartment to selectively release doses of the drug(s) to provide an efficacious dosing pattern. The microdelivery device employs a microprocessor, such as an application specific integrated circuit (ASIC), preprogrammed with a desired dosing regimen and a timing circuit, such as a quartz oscillator, in order to administer the drug(s) according to the dosing regimen. Thus, the microdelivery device is programmable to effectuate the release of the drug(s) at a desired time to maintain efficacious levels of the drug while minimizing the amount of drug which must be used.

Abstract: A water soluble biodegradable ABA-type block copolymer made up of a major amount of hydrophobic poly(lactide-co-glycolide) copolymer A-blocks and a minor amount of a hydrophilic polyethylene glycol polymer B-block, having an overall average molecular weight of between about 3100 and 4500, possesses reverse thermal gelation properties. Effective concentrations of the block copolymer and a drug may be uniformly contained in an aqueous phase to form a drug delivery composition. At temperatures below the gelation temperature of the copolymer the composition is a liquid and at temperatures at or above the gelation temperature the composition is a gel or semi-solid. The gelation temperature is preferably at or below body temperature of a warm-blooded animal. The composition may be administered to a warm-blooded animal as a liquid by parenteral, ocular, topical, transdermal, vaginal, transurethral, rectal, nasal, oral, or aural delivery means and is a gel at body temperature.

Abstract: A bioerodible controlled release dosage form is disclosed comprising a polymer formed by condensing beneficial agents having a hydroxyl functionality of two or more with diketene acetals or divinyl ethers which delivers beneficial agents to a biological environment of use. A statistically significant portion of the beneficial agent is covalently bonded within the polymer matrix.

Abstract: The method for automatic dosing of drugs utilizes a microdelivery device which may be implanted in or otherwise administered to an animal or human. A microdelivery device is configured to have a plurality of compartments, each containing at least one drug so that a plurality of doses of the drug(s) are held within the device. In accordance with the present invention, the microdelivery device selectively actuates the compartments to selectively release doses of the drug(s) to provide an efficacious dosing pattern. One primary function of the present invention is to release two or more pesticides in such a pattern that parasites are effectively controlled while preventing the development of tolerance to the drugs within the parasites. Preferably, the microdelivery device is programmable to effectuate the release of the drug(s) at a desired time to maintain efficacious levels of the drug while minimizing the amount of drug which must be used.

Abstract: The invention comprises a novel process for the spheronization of charged resins. Spherical multiparticlates are produced which range in size from 0.3 mm to 3 mm in diameter. The spherical particle product is microcrystalline-free. The process consists of the steps of mixing followed by wet granulation, spheronization and drying.

Abstract: Process for preparing and film coating a dosage form. An intagliated dosage form core is produced by inscribing one or more areas on the surface of the dosage form core prior to coating. An aqueous dispersion of a polymeric coating is then applied to the intagliated dosage form core. When placed in an environment of use, the film coating within the circumscribed region of the dosage form surface is reproducibly expelled, leaving a coated core tablet with a predefined aperture in the coating which exposes a discrete portion of the core surface to the environment of use.

Abstract: Polymers obtained by condensing polyols with divinyl orthocarbonates are useful for making bioerodible polymers for sustained release of beneficial agents.

Abstract: Bioerodible, thermoset, covalently crosslinked, elastomeric poly(ortho ester)s are disclosed. These materials are comprised of polymer chains that are interlocked in a covalent, three dimensional network which imparts dimensional stability. Use of these thermoset, covalently crosslinked materials as a drug delivery device is also disclosed.

Abstract: A microporous, cellulosic coating useful in combination with osmotically controlled drug delivery devices is disclosed. In one embodiment, this coating results from application to core tablets of a coating dispersion comprised of a synthetic latex formed by emulsification of cellulosic polymers stabilized by surfactants, containing a water-soluble pore forming agent and a plasticizer.

Abstract: A controlled release drug delivery device, comprised of swellable polymers, whose degree of swelling in an environment of use is controlled by swelling modulators blended within the polymers, is disclosed. The swelling modulators can include buffers, osmagents, surfactants or combinations thereof surrounded by a microporous coating or interspersed within individual matrices. The combination of controlled release swelling modulators with swellable polymers may be applied to regulate patterns of beneficial agent (typically a drug) release.

Abstract: Bioerodible, thermoset, covalently crosslinked, elastomeric poly(ortho ester)s are disclosed. These materials are comprised of polymer chains that are interlocked in a covalent, three dimensional network which imparts dimensional stability. Use of these thermoset, covalently crosslinked materials as a drug delivery device is also disclosed.

Abstract: A solubility modulated drug delivery device for controlled release of a therapeutically active ingredient into an environment of use is disclosed. The device comprises a core composition of a solubility modulating agent consisting of a complexing agent or a surfactant and a diffusible, water soluble, therapeutically active agent. The core composition is surrounded by a water insoluble semipermeable wall which is substantially impermeable to the core composition and permeable to the fluids in the environment of use and contains apertures through which active agent is released.

Abstract: The instant invention relates to a drug-delivery device for the controlled release of HMG-CoA reductase inhibitor salts, as the therapeutically active ingredient, into an environment of use which comprises:(A) a core composition comprising(1) a water insoluble, non-diffusible, charged resin entity, and(2) a diffusible, water soluble ionizable therapeutically active HMG-CoA reductase inhibitor salt carrying the same charge as said resin entity; and(B) an imperforate water insoluble wall surrounding said core composition and prepared from a semipermeable material substantially impermeable to core composition and permeable to the passage of an external fluid in the environment of use, with said wall having a means for release of the therapeutic agent through the water insoluble wall; or(C) a water insoluble wall surrounding said core composition and prepared from (1) a polymer material that is permeable to water but substantially impermeable to solute and (2) 0.

Abstract: The instant invention is directed to an osmotic pump comprising:(A) at least one active agent surrounded by(B) a rate controlling water insoluble wall, having a fluid permeability of 6.96.times.10.sup.-18 to 6.96.times.10.sup.-14 cm.sup.3 sec/g and a reflection coefficient of less than 1, prepared from:(i) a polymer permeable to water but impermeable to solute and(ii) 0.1 to 60% by weight, based on the total weight of (i) and (ii), of at least one pH insensitive pore forming additive dispersed throughout said wall.