Abstract: Disclosed are pharmaceutical compositions which have been modified to release pharmaceutically acceptable mycophenolate salts in the upper part of the intestinal tract and methods of treatment using the pharmaceutical compositions.

Abstract: Described is a process for making a liposomal, ion-exchange whey protein and products thereof, which result in the sustained release of amino acids into the body's circulation to generally promote skeletal muscle protein synthesis, decrease body fat in association with diet modification and improve exercise performance. The whey protein is preferably encapsulated in a liposome using a cold, or non-heated, process. After the liposomal, ion-exchange whey protein has been prepared, it is then preferably lyophilized to deliver macronutrients for use as a sports nutrition supplement and for use in medical or clinical catabolic applications.

Abstract: A storage stable aqueous solution or aqueous gel of zinc ions in the presence of bicarbonate ions is disclosed. The solution comprises: (a) a source of zinc ion, (b) a source of a stabilizing anion which can stabilize soluble zinc and bicarbonate and/or carbonate in solution; (c) a source of bicarbonate ion; and (d) a solvent therefor. The solvent comprises a major proportion of water. The zinc salt is present in an amount suitable for the intended purpose; the stabilizing anion in an amount B of at least 1.2 equivalents per equivalent of zinc ion; and the bicarbonate ion cannot exceed certain levels which are related to the level of the stabilizing anion.

Abstract: The specification describes a pharmaceutical combination consisting of dipyridamole or mopidamol and acetylsalicylic acid or the physiologically acceptable salts thereof, processes for preparing this pharmaceutical combination and the use thereof for the controlled prevention of clot formation.

Abstract: Particles are provided that are not rapidly cleared from the blood stream by the macrophages of the reticuloendothelial system, and that can be modified to achieve variable release rates or to target specific cells or organs. The particles have a core of a multiblock copolymer formed by covalently linking a multifunctional compound with one or more hydrophobic polymers and one or more hydrophilic polymers, and contain a biologically active material. The terminal hydroxyl group of the poly(alkylene glycol) can be used to covalently attach onto the surface of the particles biologically active molecules, including antibodies targeted to specific cells or organs, or molecules affecting the charge, lipophilicity or hydrophilicity of the particle. The surface of the particle can also be modified by attaching biodegradable polymers of the same structure as those forming the core of the particles.

Abstract: Modified release pharmaceutical composition and method for the treatment of inflammatory bowel diseases (IBD) such as Crohn's disease and Colitis Ulccrosa, said compositions comprising as active the ingredient 5-aminosalicylic acid (5-ASA), and being adapted for modified and targeted release so as to obtain a clinically important localized effect profile of 5-ASA by means of releasing an appropriate amount of 5-ASA in both the small and large bowel.

Abstract: This invention pertains to a dosage form for the management of epilepsies wherein the dosage form comprises administering valproic acid or a valproic acid derivative at a continuous rate over an extended time.

Abstract: A solid oral dosage form for the treatment of gastrointestinal disorders comprising a therapeutically effective amount of a pharmaceutical suitable for the treatment of gastric disorders selected from the group consisting of granules of diphenoxylate, loperamide, loperamide-N-oxide, pharmaceutically acceptable salts thereof and combinations thereof; and a therapeutically effective amount of simethicone wherein the pharmaceutical and simethicone are separated by a barrier coat on the granules which is substantially impermeable to simethicone.

Abstract: Sustained release oral solid dosage forms of opioid analgesics are provided as multiparticulate systems which are bioavailable and which provide effective blood levels of the opioid analgesic for at least about 24 hours. A unit dose of the opioid analgesic contains a plurality of substrates including the opioid analgesic in sustained release form. The substrates have a diameter from about 0.1 mm to about 3 mm.

Abstract: Liquisolid systems are acceptably flowing and compressible powdered forms of liquid medications. According to the concept of liquisolid systems, liquid lipophilic drugs, or water-insoluble solid drugs dissolved in suitable non-volatile solvents, may be converted into free-flowing and readily compressible powders by a simple admixture with selected powder excipients referred to as the carrier and coating materials. Various grades of microcrystalline or amorphous cellulose may be used as carriers, whereas very fine particle size silica powders may be used as coating materials. Based on the theory that the carrier and coating materials can retain only certain amounts of liquid and at the same time maintain acceptable flow and compression properties, a new formulation-mathematical model is provided to calculate the optimum quantities of carrier and coating materials required to yield acceptably flowing and compressible liquid/powder admixtures.

Abstract: A method for making solid granules containing aromatic, nutritional, dietary or cosmetic substances, wherein a core consisting of excipients optionally combined with active substances is formed for use as a carrier, and the core is coated in three steps with at least one layer, with one layer being formed in each step, by (a) coating the core with active substances optionally combined with excipients, (b) drying the layer and (c) screening the coated core. The method is preferably used to make granules that contain plant extracts and essential oils and may be chewed, sucked, swallowed or dissolved.

Abstract: A vaccine adjuvant composition of an oil-in-water submicron emulsion that has about 0.5 to 50% of a first component of an oil, about 0.1 to 10% of a second component of an emulsifier, about 0.05 to 5% of a nonionic surfactant, about 0.00001 to 1% of an immunogen, and an aqueous continuous phase. This submicron emulsion has a mean droplet size in the range of between about 0.03 and 0.5 .mu.m, and preferably 0.05 and 0.2 .mu.m.

Abstract: The invention relates to a peroral composition providing controlled release of a drug, the composition comprising a) a core comprising the drug and a drug release controlling agent and b) an enteric coating comprising the drug release controlling agent, wherein the drug release controlling agent consists substantially of a pH-sensitive enteric polymer. Preferably the pH-sensitive enteric polymer has a pH dissolving point of at least 6.5. The composition is preferably in the form of granules. Preferably, the composition is in the form of enteric matrix granules coated with an enteric coating. The composition releases the drug gradually in the lower gastrointestinal tract. The composition is especially suitable for the administration of 3-(3-cyanophenyl)methylene-2,4-pentanedione into the colon.

Abstract: Solid controlled-release oral dosage forms comprising a therapeutically effective amount of an opioid analgesic or a salt thereof which provide an extended duration of pain relief of about 24 hours, have a dissolution rate in-vitro of the dosage form, when measured by the USP Paddle Method of 100 rpm in 900 ml aqueous buffer at 37.degree. C. from about 12.5% to about 42.5% (by weight) active agent released after 1 hour, from about 25% to about 55% (by weight) active agent released after 2 hours, from about 45% to about 75% (by weight) opioid analgesic released after 4 hours and greater than about 60% (by weight) opioid analgesic released after 8 hours, the in-vitro release rate being substantially independent of pH and chosen such that the peak plasma level of active agent obtained in-vivo between about 2 and about 8 hours after administration of the dosage form.

Abstract: A multiple unit oral pharmaceutical dosage form having a plurality of pellets in a water soluble capsule or in a tablet compressed from the pellets, wherein each pellet contains (a) a substantially inert core, (b) an active ingredient layer over the inert core, and containing (i) a pharmacologically active particulate active ingredient, (ii) a nonembedding amount of a binder for adhering the active ingredient over the inert core, and optionally (iii) a pharmaceutically acceptable, inert adjuvant, such as colloidal silica, and (c) a coating over the active ingredient layer for retarding the release of the active ingredient from the active ingredient layer into an aqueous body fluid solvent in situ, the nonembedding amount of the binder is suitably from about 1% wt. to about 10% wt.

Abstract: Disclosed are budesonide pellets with a controlled release pattern containing, from the inside to the outside: a) neutral pellets; b) an active principle layer of micronized budesonide and one or more water-soluble auxiliaries; c) a first lacquer coating consisting of 80 to 97% of at least one lacquer insoluble in gastric fluids but soluble in intestinal fluids and 3 to 20% of at least one lacquer insoluble in both gastric and intestinal fluids; and d) a second lacquer coating consisting of at least one lacquer insoluble in gastric and intestinal fluids. The invention also relates to a process for producing budesonide pellets with a controlled release pattern.

Abstract: A drug delivery system for diltiazem-HCl comprises:a blend of fast, medium and slow release fractions of a multi-layered diltiazem bead substrate, the fast release fraction comprised of a diltiazem bead substrate layered with a polymeric membrane coating having a membrane coating weight gain of from 14 to 18 percent, the medium release fraction comprised of a diltiazem bead substrate layered with a polymeric membrane coating having a membrane coating weight gain of from 39 to 43 percent, and the slow release fraction comprised of diltiazem bead substrate layered with polymeric membrane coating having a membrane coating weight gain of from 63 to 67 percent, wherein at least one of the polymeric membrane coatings comprises a water-insoluble, slightly permeable polymer and a plasticizer triethyl citrate.

Abstract: The present invention is directed to a fluid-imbibing drug delivery device which is useful for the initial delayed delivery of an active agent formulation to a fluid environment of use, the initial delay period to startup or activation of the device being of a predetermined length of time. The delivery of the agent formulation from the dispensing device is continued until essentially all of the active agent formulation is delivered as a result of the fluid inhibition into a fluid flow path in the housing of the device and the expansion of an expansion agent in the active agent delivery chamber.

Abstract: The invention relates to pharmaceutical preparations having controlled release of active compound and to processes for their preparation, in particular for poorly soluble active compounds having problematic bioavailability.

Abstract: The object of the present invention is to obtain a targeted and controlled release of drugs, the pharmacological action and absorption of which takes place in the intestine and in particular in the ileum and in the colon.To achieve this objective the drug is coated with two membranes, one having pH dependent solubility and the other insoluble but permeable to intestinal juices.As long as the coated drug remains in the stomach and in the upper part of the intestinal tract, that is as long as the pH is lower than 5.5, it is not released.Only when it reaches an environment with a higher pH (small intestine and/or colon), the pH dependent membrane dissolves and the release of the drug can begin.From this moment the second membrane, pH-independent but permeable to intestinal juices, carries out its action which is to slow down and control the dissolution of the drug in the small intestine-colon tract.

Abstract: A softgel formulation containing retinol comprises a soft gelatin shell and a fill material within that shell containing retinol-impregnated microparticles. The fill material may be an optionally thickened silicone oil, or may be an emulsion comprising a silicone oil. Ascorbic acid may be present as ascorbic acid-impregnated microparticles and/or within the emulsion.

Abstract: A dry moisture barrier film coating composition for forming a moisture barrier film coating for pharmaceutical tablets and the like comprises polyvinyl alcohol, soya lecithin, and optionally a flow aid, a colorant, and/or a suspending agent. A liquid coating solution or dispersion for forming a moisture barrier film coating for pharmaceutical tablets and the like comprises polyvinyl alcohol, soya lecithin, water, and optionally a flow aid, a colorant, and/or a suspending agent. A method of coating pharmaceutical tablets and the like with a moisture barrier film coating comprises forming a liquid coating solution or dispersion for forming a moisture barrier film coating for pharmaceutical tablets and the like comprising polyvinyl alcohol, soya lecithin, water, and optionally a flow aid, a colorant, and/or a suspending agent, applying the coating solution or dispersion onto the tablets to form a film coating on the tablets, and drying the film coating on the tablets.

Abstract: A nifedipine formulation for oral administration is described that provides controlled, constant release of the pharmaceutical for about twenty four hours after a short delay following oral administration. There is also provided a method for preparing a controlled release formulation of nifedipine, which method includes coating pellets with multiple nifedipine-containing layers, along with an outer controlled release coating comprised of a water permeable polymer and lubricant/glidant. The pellets are then cured at an elevated temperature over several days. A method of using the formulations of the present invention for the treatment of patients is also described.

Abstract: The present invention provides oral formulations of Ranitidine Hydrochloride in the form of coated tablets and capsules which produce controlled or regulated dissolution and release at a fairly uniform rate over long periods--as long as 12 to 24 hours--to maintain Ranitidine at desired levels above the MEC.

Abstract: The present invention relates to a new form of biocompatible materials (e.g., lipids, polycations, polysaccharides) which are capable of undergoing free radical polymerization, e.g., by using certain sources of light; methods of modifying certain synthetic and naturally occurring biocompatible materials to make polymerizable microcapsules containing biological material coated with said polymerizable materials, composites of said polymerizable materials, methods of making microcapsules and encapsulating biological materials therein, and apparatus for making microcapsules containing biological cells (particularly islets of Langerhans) coated with polymerizable alginate or with a composite thereof (e.g., alginate and PEG). The present invention also relates to drug delivery systems relating to the foregoing, as well as bioadhesives and wound dressings made utilizing the foregoing technology.

Abstract: A pulsatile drug delivery system comprising of a plurality of particles is able to deliver drug in any desired patterns. A plurality of particles with multi-layer core capable of short-pulse release interlaced with long-duration release is designed for delivery of multi-agents simultaneously or sequentially, or single agent, according to a pre-programmed profile.

Abstract: Dosage forms for oral administration of a methylphenidate drug are provided. The dosage forms provide a substantially immediate dose of methylphenidate upon ingestion, followed by one or more additional doses at predetermined times. By providing such a drug release profile, the dosage forms eliminate the need for a patient to carry an additional dose for ingestion during the day. The dosage forms and methods provided are useful in administering methylphenidate and pharmaceutically acceptable salts thereof, which generally require one or more doses throughout the day.

Abstract: An enteric preparation prepared by coating a solid dosage form with a fine powder enteric coating agent while spraying a liquid plasticizer.

Abstract: A once-a-day controlled release diltiazem formulation is described which includes:(a) from 20 to 50% by weight of enteric polymeric membrane coated pellets comprising a polymer membrane coated core which comprises a biologically inert core which is coated with a first layer which consists essentially of diltiazem and a polymeric binder; and a second layer which comprises a membrane comprising a pH dependent polymeric material; and(b) from 50% to 80% by weight of delayed pulse polymeric membrane coated pellets comprising a polymeric membrane coated core which comprises a biologically inert core which is coated with a first layer which consists essentially of diltiazem and a polymeric binder and a second layer which comprises a polymeric membrane which will substantially maintain its integrity in the varying pH conditions of the gastrointestinal tract but is permeable to diltiazem; and(c) a unit dose containment system.

Abstract: The dissolution at pH 6.5 of prednisolone metasulphobenzoate or a pharmacologically acceptable salt thereof from a non-disintegratable solid enteric composition comprising the prednisolone metasulphobenzoate in an excipient matrix is increased by the presence in the matrix of a rheological modifying agent, especially croscarmellose, in an amount of at least 5 percent by weight of the composition but insufficient to cause disintegration. Preferably the composition is in the form of pellets coated with an enteric coating which is substantially insoluble below pH 7 and contained in a capsule or tablet coated with an enteric coating which is soluble at a pH in the range pH 5.5 to pH 7. The coated capsules and tablets are for use in the treatment of inflammatory bowel disease, especially ulcerative colitis and Crohn's disease.

Abstract: A controlled absorption diltiazem pellet formulation for oral administration comprises a core having diltiazem or a pharmaceutically acceptable salt thereof as the active ingredient. The core is surrounded by a coating which has only a single layer which is comprised of a relatively major proportion of talc and relatively minor proportion of sodium lauryl sulfate admixed with a minor proportion of a pharmaceutically acceptable film-forming, first polymer permeable to water and diltiazem, and a major proportion of a pharmaceutically acceptable film-forming, second polymer that is less permeable to water and diltiazem than the first polymer. The core and the coating layer both exclude organic acids. The composition of the coating layer as well as the proportion of core to coating layer are effective to permit release of the diltiazem allowing controlled absorption following oral administration.

Abstract: A once-a-day diltiazem dosage form which comprises: (a) a core element which is a compressed tablet which contains a therapeutic dose of diltiazem and an amount of a solubility modulating substance that controls the release of said diltiazem in order to provide a therapeutic level over a period of about 24 hours; and (b) on the outer surface of the core element, a sufficient amount of an enteric coating that causes the diltiazem to release at a rate that permits the use of once-a-day dosing to maintain steady state therapeutic levels of diltiazem.

Abstract: Liquisolid systems are acceptably flowing and compressible powdered forms of liquid medications. According to the concept of liquisolid systems, liquid lipophilic drugs, or water-insoluble solid drugs dissolved in suitable non-volatile solvents, may be converted into free-flowing and readily compressible powders by a simple admixture with selected powder excipients referred to as the carrier and coating materials. Various grades of microcrystalline or amorphous cellulose may be used as carriers, whereas very fine particle size silica powders may be used as coating materials. Based on the theory that the carrier and coating materials can retain only certain amounts of liquid and at the same time maintain acceptable flow and compression properties, a new formulation-mathematical model is provided to calculate the optimum quantities of carrier and coating materials required to yield acceptably flowing and compressible liquid/powder admixtures.

Abstract: A controlled release pharmaceutical composition in oral dosage unit form comprising a hard or a soft shell capsule containing a filling comprising a therapeutically effective number of active spherical granules comprising an effective amount of at least one carbonic anhydrase inhibitor active medicament, a pharmaceutically acceptable normally solid diluent adapted to form a diffusable matrix for the carbonic anhydrase inhibitor active medicament and an optional pharmaceutically acceptable excipient. A method for the preparation and for the administration of the above defined composition is provided as well.

Abstract: The present invention relates to compositions and methods for increasing the alertness of an individual through the administration of a stimulant such as xanthine or an xanthine derivative and preferably caffeine. A particular composition has one or more layers containing the stimulant arranged about the cores of microparticles. This allows the composition to release a significant portion of the stimulant within about two hours after administration so that a level of alertness can be readily achieved. Thereafter, the balance of the composition is released within about 6 to 10 hours, so that the stimulant can provide alertness during that time, but then can dissipate to levels which would not affect the individual's ability to sleep. Also, the formulation is carefully designed so that the stimulant does not accumulate in the individual's system.

Abstract: A solid oral dosage form for the treatment of gastrointestinal disorders comprising a therapeutically effective amount of a pharmaceutical suitable for the treatment of gastric disorders selected from the group consisting of cimetidine, ranitidine, famotidine, diphenoxylate, loperamide, loperamide-N-oxide, pharmaceutically acceptable salts thereof and combinations thereof; and a therapeutically effective amount of simethicone wherein the pharmaceutical and simethicone are separated by a barrier which is substantially impermeable to simethicone.

Abstract: A composition, and methods of forming and using said composition, for the sustained release of non-aggregated, biologically active, erythropoietin (EPO). The sustained release composition of this invention comprises a polymeric matrix of a biocompatible polymer and particles of biologically active, aggregation-stabilized EPO, wherein said particles are dispersed within the biocompatible polymer.The method of the invention for producing a composition for the sustained release of biologically active EPO, includes dissolving a biocompatible polymer in a polymer solvent to form a polymer solution, dispersing particles of biologically active, aggregation-stabilized EPO in the polymer solution, and then solidifying the polymer to form a polymeric matrix containing a dispersion of said EPO particles.The method for using a composition of the invention is a method for providing a therapeutically effective blood level of biologically active, non-aggregated erythropoietin in a subject for a sustained period.

Abstract: The present invention provides novel hydrogel-forming, self-solvating, absorbable polyester copolymers capable of selective, segmental association into compliant hydrogels upon contacting an aqueous environment.

Abstract: The novel diclofenac preparation with controlled release is in the form of pellets. The active ingredient, applied to inert pellets, is coated with a membrane layer which contains, in addition to 35-65% by weight of a water-insoluble polymer, 5-20% by weight of at least one water-soluble and/or water-insoluble pore-forming agent and 20-50% by weight of adjuncts. The pore-forming agents permit a very uniform release of diclofenac such that administration twice a day is sufficient. A film coating resistant to gastric juice is applied over the membrane layer.

Abstract: A composition for oral preparations, having a complex formed by dispersing or dissolving an unpleasantly tasting basic drug and a functional polymer compound in a substance having a low melting point, 10 to 70% by weight, based on the composition, of sugar alcohol and 0.1 to 7% by weight, based on the composition, of basic oxide. The composition for oral preparation is excellent in masking unpleasantly tasting basic drugs and has excellent performance in biological use.

Abstract: Thermoplastic materials which comprise a copolymer of(A) 16 to 40 wt % of acrylic and/or methacrylic acid;(B) 30 to 80 wt % of methyl acrylate; and(C) 0 to 40 wt % of another alkyl ester of acrylic and/or methacrylic acid and perhaps conventional auxiliaries for drug coatings are suitable for the production of drug coatings which are soluble in intestinal juices, such as tablet coatings, dies, films, capsules, or multipart dosage units.

Abstract: The present invention relates to compositions and methods for increasing the alertness of an individual through the administration of a stimulant such as xanthine or an xanthine derivative and preferably caffeine. A particular composition has one or more layers containing the stimulant arranged about the cores of microparticles. This allows the composition to release a significant portion of the stimulant within about two hours after administration so that a level of alertness can be readily achieved. Thereafter, the balance of the composition is released within about 6 to 10 hours, so that the stimulant can provide alertness during that time, but then can dissipate to levels which would not affect the individual's ability to sleep. Also, the formulation is carefully designed so that the stimulant does not accumulate in the individual's system.

Abstract: The present invention relates to a pharmaceutical composition in a unit dosage form for peroral administration in a human or lower animal, having a gastrointestinal tract comprising a small intestine and a colon with a lumen therethrough having an inlet to the colon from the small intestine, comprising:a. a safe and effective amount of a therapeutically active agent incorporated into or coated on the surface of a dosage form selected from the group consisting of a spherical substrate, an elliptical substrate, a hard capsule, or a compressed tablet, with a maximum diameter of about 3 mm to about 10 mm; andb. an enteric polymer coating material comprising at least one inner coating layer and one outer coating layer;wherein the dosage form has a smooth surface free from edges or sharp curves; the elliptical substrate and the hard capsule have a ratio of the long to short diameters of no greater than about 1.

Abstract: A solid oral dosage form for the treatment of gastrointestinal disorders comprising a therapeutically effective amount of a pharmaceutical suitable for the treatment of gastric disorders selected from the group consisting of cimetidine, ranitidine, famotidine, diphenoxylate, loperamide, loperamide-N-oxide, pharmaceutically acceptable salts thereof and combinations thereof; and a therapeutically effective amount of simethicone wherein the pharmaceutical and simethicone are separated by a barrier which is substantially impermeable to simethicone.

Abstract: The present invention relates to a pharmaceutical composition in a unit dosage form for peroral administration in a human or lower animal, having a gastrointestinal tract comprising a small intestine and a colon with a lumen therethrough having an inlet to the colon from the small intestine, comprising:a. a safe and effective amount of rapidly dissolving bisacodyl incorporated into or coated on the surface of a dosage form selected from the group consisting of a spherical substrate, an elliptical substrate, a hard capsule, or a compressed tablet, with a maximum diameter of about 3 mm to about 10 mm; andb. an enteric polymer coating material comprising at least one inner coating layer and one outer coating layer;wherein the dosage form has a smooth surface free from edges or sharp curves; the elliptical substrate and the hard capsule have a ratio of the long to short diameters of no greater than about 1.

Abstract: An oral pharmaceutical composition is described for targeted slow release in the treatment of inflammatory bowel diseases. Also described are pharmaceutical compositions for peroral treatment targeted to different areas of the intestinal tract afflicted by ulcerative colitis and certain aspects of Crohn's disease.

Abstract: A programmed release pharmaceutical dosage form comprising a core, containing the active ingredient, coated by a hydrophobic layer is described. Such dosage forms release the active ingredient after a pre-established no-release interval which does not depend on physiological factors.

Abstract: This invention is directed towards pellets and a process for manufacturing pellets of diltiazem HCl having a dissolution kinetic independent from pH.

Abstract: A biocompatible microcapsule containing living cells encapsulated in a membrane is disclosed. The membrane is a complex formed by the cohesion of two polymer layers. An inner layer comprises a substrate biopolymer and an outer layer comprises a synthetic polyelectrolyte having an electrolytic charge opposite that of the substrate biopolymer. Droplets of a solution of substrate biopolymer containing a suspension of living cells can be added to a solution comprising the synthetic polyelectrolyte to form the encapsulates. The membrane is formed by the cohesion of the oppositely-charge polymer layers to form a complex of substrate biopolymer and synthetic polyelectrolyte. Preferably, the inner layer contains a cationic biopolymer, such as collagen modified to have a pKI of 9, or an anionic biopolymer such as esterified or modified hyaluronic acid.

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.