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 process for producing a pharmaceutical composition is disclosed. In the process, 1 part by weight of a physiologically inert powdery additive, 0.001-1 part by weight of a macromolecular additive per part by weight of said insert powdery additive, and at least one drug substance are used as ingredients and processed en bloc by means of a multi-screw extruder. The drug substance used in the process can be selected from the following group: subliminable drug, volatile drug, drug hydrolyzable in the presence of water, drug which develops whiskers, and hygroscopic or deliquescent drug. The process confers increased physicochemical stability to the pharmaceutical composition and the drug substance contained therein.

Abstract: The invention relates to sugar-coated dosage units comprising a steroid having two hydrogen atoms at position 3 of the steroid skeleton, such as desogestrel, allylestrenol, ethylestrenol, or lynestrenol, to a process for the manufacture of such dosage units, and a use of sugar-coated compositions for providing stable dosage units comprising said steroid.

Abstract: Drug formulations comprising coated, very sparingly water-soluble drugs for inhalational pharmaceutical forms, and process for their preparation.Drug formulations comprising micronized particles of very sparingly water-soluble drugs which are coated with a natural, physiologically acceptable ampholytic surfactant soluble in water to give a micellar/colloidal solution, and a process for the preparation of these drug formulations, are described. When placed in an appropriate final container and after the addition of a chlorine-free, partially fluorinated propellant gas liquefiable under pressure, these formulations are suitable for inhalation.

Abstract: A method for substantially reducing the range in daily dosages required to control pain in approximately 90% of patients is disclosed whereby an oral solid controlled release dosage formulation having from about 10 to about 40 mg of oxycodone or a salt thereof is administered to a patient. The formulation provides a mean maximum plasma concentration of oxycodone from about 6 to about 60 ng/ml from a mean of about 2 to about 4.5 hours after administration, and a mean minimum plasma concentration from about 3 to about 30 ng/ml from about 10 to about 14 hours after repeated "q12h" (i.e., every 12 hour) administration through steady-state conditions.

Abstract: The invention relates to a delayed action preparation which comprises a core comprising a drug and a swelling agent and an outer membrane comprising a biodegradable high molecular weight substance characterized in that the swelling agent is contained in a sufficient amount to cause a explosion of the outer membrane of biodegradable high molecular weight substance at a definite time after administration. This preparation provides for free control over the timing of drug release and is suited for administration not only by the oral route but also by the intramuscular, subcutaneous and other routes.

Abstract: A method for the production of microcapsules embedded with pharmaceuticals, peptides, proteins, enzymes and vaccines, which uses biodegradable solvents, and microcapsules free of toxic residual solvents is described. The microcapsules are obtained by spraying of a solution, suspension or water-in-oil dispersion of active materials and biodegradable polymers.

Abstract: The present invention concerns the use of microspheres for therapeutic embolization consisting of a hydrophilic acrylic copolymer coated with a cell adhesion promoter.

Abstract: A novel granular drug delivery system having a gel-forming dietary fiber that can be made into a an orally-ingestible dispersion by admixture with a liquid that can deliver an effective dose of a pharmaceutically-active compound. The granular drug delivery system comprises granules consisting essentially of a pharmaceutically active compound, and a gel-forming dietary fiber, the granules being coated with at least one of the following: a gel-forming dietary fiber, a starch or a protein. The composition may further include a mineral salt that releases a physiologically-acceptable gas upon ingestion. The composition of the granular drug delivery system will deliver microgram quantities of a pharmaceutically-active compound in an orally-ingestible dispersion without forming a thick gel and without forming "hot" and "cold" spots of the pharmaceutically-active compound.

Abstract: The present invention concerns the use of microspheres for therapeutic embolization consisting of a hydrophilic acrylic copolymer coated with a cell adhesion promoter.

Abstract: Particles, preparation methods therefor, and compositions containing same. The particles include at least one esterified polysaccharide and at least one polyamine, as well as at least one gellable polysaccharide when neither the esterified polysaccharide nor the polyamine can be gelled under the selected operating conditions. Said particle includes, at least on its surface, a membrane consisting of the product of the transacylation reaction between the esterified polysaccharide and said polyamine within an optionally gellable gel, said reaction causing the formation of covalent amide bonds. Such particles may be used to encapsulated various active principles useful in the fields of cosmetics, pharmaceuticals and agri-foodstuffs, enzymes, cells and micro-organisms.

Abstract: A method of fabricating hydrogel particles within liposomes, which entails: a) encapsulating an effective amount of each of one or more hydrogel substances and one or more release agents in liposomes in a liquid medium, b) removing any unencapsulated hydrogel substances and release agents from the liquid medium, c) adding initiator to the liquid medium and into the liposomes, thereby initiating reaction of the one or more hydrogel substances, whereby hydrogel particles are formed in the liposomes, and d) removing any extra-liposomal initiator from the medium.

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

Abstract: This invention relates to a novel method for preparing pesticide microcapsules in which the release rate and the release period of the pesticide are controlled. A process has been discovered for encapsulating a trace amount of pesticide with a urea-formaldehyde resin, mechanically stirring the resin in the presence of vegetable oil and the pesticide and reacting the mixture under suitable conditions to form a desired pesticide microcapsule.

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: A method for substantially reducing the range in daily dosages required to control pain in approximately 90% of patients is disclosed whereby an oral solid controlled release dosage formulation having from about 10 to about 40 mg of oxycodone or a salt thereof is administered to a patient. The formulation provides a mean maximum plasma concentration of oxycodone from about 6 to about 60 ng/ml from a mean of about 2 to about 4.5 hours after administration, and a mean minimum plasma concentration from about 3 to about 30 ng/ml from about 10 to about 14 hours after repeated "q12h" (i.e., every 12 hour) administration through steady-state conditions.

Abstract: The improved pharmaceutical preparation for oral administration which is adapted to release the drug at appropriate sites in the intestines comprises: a core that comprises an active ingredient and a pharmaceutically acceptable excipient, a first layer that covers the core and which comprises an enteric or water-soluble ingredient and an optional insoluble ingredient, a second layer that covers the first layer and which comprises a non-enteric ingredient that dissolves upon reacting with at least one ingredient in the core, and a third layer that covers the second layer and which comprises an enteric ingredient. This preparation is characterized in that it will not release the active ingredient until after it reaches a desired site in the intestines and that, in addition, it is capable of controlling the rate at which the active ingredient is released after it has reached the desired site.

Abstract: In the pharmaceutical formulation of at least one alkali-sensitive active substance with an effervescent system, the carbonate component is embedded in at least one edible, organic acid and is preferably covered by said acid or by another acid. The active substance is embedded in at least one of the following compounds: an edible, organic acid, a higher alcohol, a hydrocolloid or a relatively long-chain polyvinylpyrrolidone, preferably covered with at least one of the stated compounds. The contact zone between active substance and effervescent system should have a pH of not more than 4.5. Both effervescent system particles and active substance particles, which are embedded or optionally covered in this manner, may be applied to carrier crystals of the same or another acid. The mixture is preferably pressed to give tablets. The acid provided for the embedding or covering may contain 0.1 to 3 mg of ethylenediaminetetraacetic acid per tablet.

Abstract: This invention describes a device for peroral administration of a therapeutic agent which is capable of existing in an unionized therapeutically active form. The device comprises a reservoir comprising the therapeutic agent in ionized form, which reservoir has a wall permeable to un-ionized material and impermeable to ionized material; and a solid material which upon uptake of water is converted to a buffer; the solid material having, on uptake of water, a pH which determines the rate of permeation of the therapeutic agent in un-ionized form through the reservoir wall. The device enables the release of the therapeutic agent to be controlled by the pH of the buffer and, if desired, the composition of the reservoir walls. The composition of the surrounding aqueous medium does not affect the rate of release.

Abstract: This invention concerns delivery vehicles entrapping active materials suspended in a water immiscible carrier. Methods of making these materials, preferably using a carboxymethylcellulose support martrix, are disclosed. The vehicles of the invention are especially well adapted to delivery of incompatible actives that can be entrapped separately and kept separately until release from the vehicle.

Abstract: A method for substantially reducing the range in daily dosages required to control pain in approximately 90% of patients is disclosed whereby an oral solid controlled release dosage formulation having from about 10 to about 40 mg of oxycodone or a salt thereof is administered to a patient. The formulation provides a mean maximum plasma concentration of oxycodone from about 6 to about 60 ng/ml from a mean of about 2 to about 4.5 hours after administration, and a mean minimum plasma concentration from about 3 to about 30 ng/ml from about 10 to about 14 hours after repeated "q12h" (i.e. every 12 hour) administration through steady-state conditions.

Abstract: A fungicide containing, as an active ingredient, a metal complex of the formula (I),[M{W--Si(OA.sup.1).sub.k A.sub.3-k.sup.2 }.sub.g ]Z.sub.f (I)wherein M, W, A.sup.1, A.sup.2, k, f, g and Z are as defined in the bore formula (I) of claim 1; and use thereof for various fungicidal substances.

Abstract: A novel granular drug delivery system having a gel-forming dietary fiber that can be made into a an orally-ingestible dispersion by admixture with a liquid that can deliver an effective dose of a pharmaceutically-active compound. The granular drug delivery system comprises granules consisting essentially of a pharmaceutically active compound, and a gel-forming dietary fiber, the granules being coated with at least one of the following: a gel-forming dietary fiber, a starch or a protein. The composition may further include a mineral salt that releases a physiologically-acceptable gas upon ingestion. The composition of the granular drug delivery system will deliver microgram quantities of a pharmaceutically-active compound in an orally-ingestible dispersion without forming a thick gel and without forming "hot" and "cold" spots of the pharmaceutically-active compound.

Abstract: The present invention relates to micro-capsules constituted by a solid envelope consisting of a layer of coating materials including at least one gastro-resistant polymer, said solid envelope containing an oily liquid.

Abstract: A process for producing pellets which are markedly spherical and have a particle size in the range from 0.1 to 4 mm and an apparent density above 0.5 g/cm.sup.3, and which are composed of 90-100% by weight of an ephedrine derivative and 0-10% by weight of a pharmaceutical aid, entails suspending ephedrine derivative powder with an average particle size of from 0.5 to 50 .mu.m at 0.degree.-90.degree. C. with stirring in a water-immiscible non solvent with a boiling point in the range from 60.degree. to 160.degree. C., adding 5-60% by weight, based on the ephedrine derivative, of an agglomerating liquid while continuing stirring, and, if there has been previous heating, cooling to from -5 to 25.degree. C. at 5-40K per hour, with the stirring speed being adjusted after the agglomeration of the powder particles to a value which is necessary for the required average particle size, and removing and drying the resulting pellets.

Abstract: A fragrance sampler has an image of a perfume bottle printed on a paper sheet, the image including a body portion and a cap portion. The part of the sheet on which the cap is printed is removable from the rest of the sheet and is connected to a strip on which microcapsules enclosing droplets of the displayed perfume are adhered. The strip is located underneath the sheet on which the image is printed and is concealed from view until removed along with the cap portion. Effective light adhesion is provided by using gelatin-walled microcapsules, which adhere to the strip without use of binder when applied from an aqueous slurry. Upon detaching the cap portion and pulling it away from the sampler, the perfume-carrying strip is also removed, allowing the strip to be used as an applicator for placing sample particles on the skin of the user. The sampler effectively simulates the bottle used for a particular perfume and correlates the visual image of the bottle with a fragrance that is delivered.

Abstract: A prolonged-release unit dosage formulation or pharmaceutical composition, preferably in tablet form, is described. The composition consists essentially of a gel-forming fiber, preferably hydrocolloid-coated, a biologically-absorbable drug or other active therapeutic agent which is also preferably hydrocolloid-coated, a mineral salt which releases a physiologically-acceptable gas upon ingestion, preferably carbon dioxide, e.g., a mineral carbonate or bicarbonate, and optionally an organic or phosphoric acid and a dextrose or like soluble sugar. The fiber-containing composition, when in the form of a tablet or other unit dosage form together with the drug or agent and the stated disintegrants, provides a unique, efficient and controllable prolonged-action drug-delivery system.

Abstract: Cholesterol reductase is administered to humans to convert cholesterol to coprostanol in the small intestine thus decreasing the bloodstream cholesterol level.

Abstract: The present invention relates to a novel oral dosage form of a bisphosphonic active ingredient for use in treatment of diseases involving bone resorption and formulated in an enteric-coated form for administration to subjects exhibiting upper gastrointestinal tract sensitivity to bisphosphonic acid compounds.

Abstract: A process for the preparation of a dry adsorbable extract of at least one active ingredient, comprising the steps of: first, preparing an extract of the active ingredient in a solvent medium specific to the active ingredient; second coating granules of an absorbent carrier with the extract; third drying and calibrating to a predetermined size the coated granules; and finally absorbing the coated granules produced in step 3 in and on porous excipient nebulized microgranules, which have cavities and ducts which are partially filled by the coated granules, with a ratio of between 5 and 20 parts by weight of coated granules to 100 parts microgranules.

Abstract: A controlled release formulation for use with a variety of drugs or hormones are formed in microspherical form. The drug or hormone, e.g. bovine somatropine, is suspended in a polymer matrix. The polymer matrix is formed from at least two highly water soluble biodegradable polymers, selected for example from starch, crosslinked starch, ficoll, polysucrose, polyvinyl alcohol, gelatine, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl-ethyl cellulose, hydroxypropyl-methyl cellulose, sodium carboxymethyl cellulose, cellulose acetate, sodium alginate, polymaleic anhydride esters, polyortho esters, polyethyleneimine, polyethylene glycol, methoxypolyethylene glycol, ethoxypolyethylene glycol, polyethylene oxide,poly(1,3 bis(p-carboxyphenoxy) propane-co-sebacic anhydride, N,N-diethylaminoacetate, block copolymers of polyoxyethylene and polyoxypropylene. The microspheres are coated with a (d,1 lactide-glycolide) copolymer.

Abstract: An oral dosage form of morphine is formulated by powder-layering an homogeneous mixture of morphine sulfate and hydrous lactose impalpable onto inert beads to obtain a multiparticulate product. A plurality of the powder-layered beads may be administered either in immediate release form or in an extended release form by coating with a hydrophobic material.

Abstract: The taste of orally administered drugs is masked by coating the drug with a polymeric membrane which is soluble only at a pH of 5 or more. An acid substance is included in the formulation containing the coated drug to reduce or prevent the dissolution of the membrane in the oral cavity.

Abstract: A physicochemically stable pharmaceutical matrix composition is provided comprising: a pharmaceutical active and a water insoluble aliphatic or fatty acid ester, preferably stearyl stearate; a taste mask carrier for pharmaceutical actives comprising a taste masking effective amount of an aliphatic or fatty acid ester; and a method for preparing a pharmaceutical matrix without the use of organic and/or volatile solvents comprising the steps of: melting an aliphatic or fatty acid ester; admixing at least one pharmaceutical active with the molten aliphatic or fatty acid ester; and solidifying the admixture to produce a pharmaceutical matrix composition. The matrix is composed of an aliphatic, or fatty acid, ester that has a low melting point (50.degree.-100.degree. C.) and the melt exhibits: low viscosity, recongeals rapidly when cooled, does not exhibit polymorphism, and has good mold release properties.

Abstract: This invention provides a homogeneous antiperspirant cosmetic stick or roll-on product containing a deodorant ingredient which consists of particles that contain multiple fine crystallites of a bicarbonate compound encapsulated with a hydrophilic polymer coating that lowers the relative density of the particles and improves the dimensional stability of the cosmetic product.

Abstract: The present invention relates to polymeric microspheres as injectable, drug-delivery systems for use to deliver bioactive agents to sites within the central nervous system, and for the stimulation of nerve fiber growth by implanting such microspheres within the central nervous system of a patient.

Abstract: This invention discloses a composition comprised of nanoparticles having a surface modifier adsorbed on the surface thereof and a non-ionic cloud point modifier associated therewith, which cloud point modifier is present in an amount-sufficient to increase the cloud point of the surface modifier. A preferred surface modifier is a poloxamine such as Tetronic 908, and preferred non-ionic cloud point modifiers include polyethylene glycol, propylene glycol, ethanol, hydroxypropylcyclodextrin and/or glycerol. This invention further discloses a method of making nanoparticles having a surface modifier adsorbed on the surface and a non-ionic cloud point modifier associated therewith, comprised of contacting said nanoparticles with the cloud point modifier for a time and under conditions sufficient to increase the cloud point of the surface modifier.

Abstract: A high-fiber, consumable bulk fiber composition, which may be used as a laxative, comprises powdered psyllium husks agglomerated with a water soluble, low viscosity gum, preferably gum acacia, to form a dry, free-flowing, water dispersible dietary fiber combinate. To form the dietary fiber combinate, the powdered psyllium husks are mixed with an aqueous solution of the water soluble, low viscosity gum, preferably by fluid bed agglomeration, and dried. The composition is employed to treat constipation by ingesting an effective amount of the dietary fiber combinate dispersed in water.

Abstract: A fungicidal composition in particulate or powder form wherein each active particle thereof comprises a fungicidally active compound, especially an acrylamide such as dimethomorph, dispersed in a polymer material having a melting point below the degradation temperature of the compound. The fungicidal composition is particularly useful in the form of a wettable powder or a suspension concentrate.

Abstract: An oral composition which is adapted to be dispersed in an aqueous carrier substantially immediately prior to administration comprises a multiplicity of particles comprising an active substance, the particles being combined with one or more gelling or swelling agents capable of forming a viscous medium around the particles in an aqueous carrier as well as being provided with a masking surface layer when dispersed in the aqueous carrier. This serves to mask uneven surfaces on the particles and prevent them from adhering to oral mucosa when the composition is ingested and thus makes it easier to administer large dosages of an active substance. The masking surface layer is preferably provided by an increased viscosity of the viscous medium in the immediate vicinity of the particles relative to the viscosity of the surrounding aqueous carrier.A ready-to-use composition is prepared by mixing the composition with an aqueous carrier substantially immediately prior to administration of the composition.

Abstract: A method for the treatment of gastrointestinal disorders associated with Helicobacter pylori infections which comprises administering to a patient an orally effective amount of triclosan is disclosed. The triclosan may be administered in the form of powders, granules, spheroids or liquids, or in unit dosage form as capsules or tablets containing 1 to 100 mg, preferably 10 to 60 mg, of triclosan. The triclosan may also be administered in gastric sustained release medicaments either as raft forming tablets or liquids, optionally to be co-administered with a solid pharmaceutically acceptable carboxylic acid or acid salt, or as mucoadherent-coated granules or spheroids.

Abstract: Microencapsulates containing antiperspirant salts, microencapsulates in conjunction with bioadhesives, and antiperspirant/deodorant compositions containing the microencapsulates of the invention.

Abstract: A solid controlled release, oral dosage form, the dosage form comprising a therapeutically effective amount of oxycodone or a salt thereof in a matrix wherein the dissolution rate in vitro of the dosage form, when measured by the USP Paddle Method of 100 rpm in 900 ml aqueous buffer (pH between 1.6 and 7.2) at 37.degree. C. is between 12.5% and 42.5% (by weight) oxycodone released after 1 hour, between 25% and 55% (by weight) oxycodone released after 2 hours, between 45% and 75% (by weight) oxycodone released after 4 hours and between 55% and 85% (by weight) oxycodone released after 6 hours, the in vitro release rate being independent of pH between pH 1.6 and 7.2 and chosen such that the peak plasma level of oxycodone obtained in vivo occurs between 2 and 4 hours after administration of the dosage form.

Abstract: A feed additive granule for ruminants comprising a granulated physiologically active substance as the core, a first coating layer placed on the surface of said core, said first coating layer containing a high molecular substance which dissolves or swells in water in an acidic pH region of not greater than 5.5 and is stable in a pH region of 5.6 to 8.0, and a second coating layer placed on said first coating layer, said second coating layer being of a substance which is stable in an acidic pH region of not greater than 5.5, dissolves or swells in water in a pH region of 5.6 to 8.0 and is acceptable to ruminants, and some modifications thereof, as well as feed for ruminants comprising such a novel feed additive.

Abstract: A sustained-release pranoprofen preparation is disclosed. The preparation comprises an effective amount of pranoprofen and one or more sustained-release components selected from the group consisting of oily components, water-soluble components, water-insoluble components, and intestinally soluble components. It controls release of pranoprofen and lowers the maximum pranoprofen concentration in blood, maintaining its concentration in blood at a certain level for a long period of time. It reduces risks of side effects and can effectively treat diseases with dosing once or twice a day.

Abstract: A composition for increased bioavailability of Vitamin E. The composition contains a Vitamin E material, a surface active agent, an inert carrier, and, optionally, a flow agent.

Abstract: A salt sensitive capsule has been developed which dissolves in the mouth and releases the encapsulated internal ingredient(s). The outer salt sensitive shell maintains its integrity when kept at a preselected aqueous salt concentration. When introduced into the mouth, the degree of salinity is lower and causes the shell to disassociate and release the internal component. The capsules may be associated with an adhesive system so that the capsules are topically applied to mouth tissue. The adhesive system is compatible with maintenance of the salt sensitive shell.

Abstract: The surface of micronized and hydrophilized powder particles of a hydrophobic or sparingly soluble substance is covered with a cohesive layer of not more than 0.1 part by weight of surfactant in not more than 10 parts by weight of a binder (based on 100 parts by weight of the substance). A sparingly soluble or insoluble antibiotic is converted to instant granules or instant tablets, while a hydrophobic, moderately soluble to readily soluble pharmaceutical substance, such as, for example, acetylsalicylic acid or paracetamol, is converted to effervescent granules or effervescent tablets. The particles are preferably applied to carbohydrate crystals by means of a binder. The preparation is carried out by a method in which a solution which contains at least one surfactant in an amount of 0.01 to 0.

Abstract: An oral composition which is adapted to be dispersed in an aqueous carrier substantially immediately prior to administration comprises a multiplicity of particles comprising an active substance, the particles being combined with one or more gelling or swelling agents capable of forming a viscous medium around the particles in an aqueous carrier as well as being provided with a masking surface layer when dispersed in the aqueous carrier. This serves to mask uneven surfaces on the particles and prevent them from adhering to oral mucosa when the composition is ingested and thus makes it easier to administer large dosages of an active substance. The masking surface layer is preferably provided by an increased viscosity of the viscous medium in the immediate vicinity of the particles relative to the viscosity of the surrounding aqueous carrier. A ready-to-use composition is prepared by mixing the composition with an aqueous carrier substantially immediately prior to administration of the composition.

Abstract: A pharmaceutical composition useful for treating hypercholesterolemia comprising a bile acid sequestrant resin such as cholestyramine and cholestipol maintained in a semipermeable water-insoluble material; wherein said semipermeable material enables bile acids from the digest tract to contact and bind to said resin while preventing substances having a higher molecular weight than bile acids from contacting said resin material. A method for treating hypercholesterolemia using the inventive composition is also disclosed.