Abstract: Disclosed is a method for the therapeutic treatment of pain related to wind up in a human or animal. The method of the invention is practiced by administering to the subject an effective amount of an analgesic pharmaceutical composition which includes a NMDA receptor antagonist in an immediate release form combined with an NMDA receptor antagonist in a sustained release form. The immediate release form and sustained release forn are present in sufficient amounts to diminsh or abolish wind up.

Abstract: A pharmaceutical composition is provided for the oral administration of an NSAID and a prostaglandin. The composition is a solid dosage form wherein the NSAID is enterically coated and the prostaglandin is present along with an effective stabilizing amount of a prostaglandin stabilizing agent such as hydroxypropyl methylcellulose or polyvinylpyrrolidone. Exemplary dosage forms are bilayer tablets in which the prostaglandin is misoprostol and the NSAID is diclofenac, piroxicam, or a pharmaceutically acceptable salt thereof. Methods for using the composition to treat NSAID-responsive conditions, disorders and diseases are provided as well.

Abstract: Disclosed are compositions including an adenosine analog, wherein the composition comprises a dosage form suitable for oral (co)administration. Also disclosed are compositions including adenosine analogs, wherein the composition is in a dosage form including a pill, capsule, lozenge, or tablet, and compositions including adenosine analogs, wherein the composition is in a dosage form comprising a liquid. Additionally disclosed are methods of administering the inventive composition, and kits including the inventive compositions.

Abstract: This invention provides a pharmaceutical composition comprising a mycophenolate salt, the composition being adapted to release mycophenolate in the upper part of the intestinal tract.

Abstract: The invention relates to a method for the determination of dose-level characteristics, such as physicochemical properties, functionality and/or quality, of a multiple unit system comprising a plurality of individual subunits (12). A number of said subunits (12) are individually analysed for obtaining precise characteristics for each individually analysed subunit (12). Said dose-level characteristics of the multiple unit system are determined based the thus-obtained precise characteristics for each individually analysed subunit (12). The invention also relates to an industrial process in which this method is used, and to the use of the claimed method in a process for designing a multiple unit system formulation product.

Abstract: An oral pharmaceutical modified release multiple-units composition for the administration of an analgesically effective amount of an opoid. The composition comprises at least two fractions wherein individual units containing an opoid are coated with a sustained release coating. A first fraction is adapted to relatively fast release while a second fraction is adapted to a delayed release. Such compositions make possible to obtain both a relatively fast onset of the analgesic effect and the maintenance of analgesically active plasma concentration for a relatively long period of time. The invention further relates to a process for the preparation of a composition according to the invention.

Abstract: The present invention relates to a composition, particularly adapted to oral administration, substantially free of alkaline-reacting compounds. The composition comprises (a) a core containing an acid-labile benzimidazole active principle, where the core comprises a plurality of nuclei and the active principle mixed together and then compressed together, and where the active principle is not in the form of an alkaline salt; (b) an intermediate layer; and (c) an enteric layer; provided that omeprazole is not the benzimidazole active principle. A process for preparing the composition is also disclosed.

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 at 100 rpm at 900 ml aqueous buffer (pH between 1.6 and 7.2) at 37.degree. C. of from about 12.5% to about 42.5% (by wt) opioid released after 1 hour, from about 25% to about 65% (by wt) opioid released after 2 hours, from about 45% to about 85% (by wt) opioid released after 4 hours, and greater than about 60% (by wt) opioid released after 8 hours, the in-vitro release rate being substantially independent of pH and chosen such that the peak plasma level of said opioid analgesic obtained in-vivo occurs from about 2 to about 8 hours after administration of the dosage form.

Abstract: An oral pharmaceutical composition of a reversible proton pump inhibitor in pellet or tablet form, wherein the reversible proton pump inhibitor is at least partly in slow-release form, is distinguished, on combined administration with an antimicrobially-active ingredient, by an enhanced action of rapid onset against disorders caused by Helicobacter.

Abstract: Colonic evacuation, treatment of small bowel bacterial overgrowth or irritable bowel syndrome or treating acute or chronic bacterial bowel infection comprises administering an osmotic colonic evacuant in solid form, preferably a mixture of sodium dihydrogen phosphate and disodium hydrogen phosphate or a sulfate based laxative comprising a picosulfate, together with a diluent.

Abstract: An extended release acetaminophen composition comprises a plurality of discrete particles containing acetaminophen which, when contained within a gelatin capsule and assayed in a USP Apparatus I rotating basket at 50 rpm in 900 mL of phosphate buffer at pH 5.8 and 37.degree. C., exhibits about 40 percent to about 53 percent acetaminophen dissolution at one-half hour, about 50 percent to about 68 percent dissolution at 45 minutes, about 57 percent to about 77 percent acetaminophen dissolution at one hour, and about 82 percent to about 92 percent acetaminophen dissolution at two hours. After six hours, the contemplated extended release acetaminophen composition exhibits substantially complete dissolution. A process for treating a human patient with the extended release acetaminophen composition is also disclosed.

Abstract: The method of making a solid drug with controlled effective ingredient delivery for oral administration includes selecting a predetermined number of at least three of four compressed compositions containing an effective ingredient or effective ingredient combination defined by their release profile of effective ingredient and/or effective ingredient combination. The solid drug or medicinal preparation is formed according to known methods requiring only comparatively small apparatus expense and minimal time. Perorally administered solid drugs are made by this process which can provide widely varying pharmaceutically-required release profiles of effective ingredients or effective ingredient combinations, for example delayed release, uniformly maintained release or pulsatile release adjusted to fit a special rhythm.

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: Tablet formulations having a structure comprising compacted granulates of a mixture of a medicament and an intra-granular disintegrant, the granulates being compacted together into a tablet with an extra-granular disintegrant and optional extra-granular lubricant and excipients.

Abstract: A composition, comprising (a) microcrystalline cellulose; and (b) a compressibility augmenting agent which (i) physically restricts the proximity of the interface between adjacent cellulose surfaces; or (ii) inhibits interactions between adjacent cellulose surfaces; or (iii) accomplishes both (i) and (ii) above, is disclosed. The composition is in the form of agglomerated particles of microcrystalline cellulose and the compressibility augmenting agent in intimate association with each other.

Abstract: Liquisolid systems are acceptably flowing and compressible powdered forms of liquid medications. According to the concept of liquisolid systems, liduid 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.

Abstract: Compositions and methods for preserving untanned animal hides, wherein the compositions comprise 50-95% (w/w) of a polyether antibiotic and 5-25% (w/w) of a surface-acting agent. In these compositions, greater than 90% of the polyether antibiotic has a particle size of less than 25 microns, and the surface-acting agent is present in an amount that is effective to disperse the polyether antibiotic uniformly in an aqueous suspension.

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. In addition, multi-particulate oral dosage forms containing therapeutically effective agents containing a plurality of pharmaceutically acceptable inert beads powder-layered with homogeneous mixture of a therapeutically effective agent and hydrous lactose impalpable are also disclosed. A method of preparing the dosage forms as well as a method preparing spheroids containing the homogeneous mixture of therapeutically effective agent and hydrous lactose impalpable are also disclosed.

Abstract: The invention provides an immediate-release fenofibrate composition comprising (a) an inert hydrosoluble carrier covered with at least one layer containing fenofibrate in a micronized form having a size less than 20 .mu.m, a hydrophilic polymer and, optionally, a surfactant, the polymer making up at least 20% by weight of (a); and (b) optionally one or several outer phase(s) or layers(s). The invention also provides a method for preparing said composition.

Abstract: A pharmaceutical composition in the form of a tablet or a capsule for the controlled release of diltiazem, comprises about 30 to about 97% by weight of a hydrophilic polymer, about 0.5 to about 30% by weight of an enteric (pH-dependent) polymer, and about 2.5 to about 60% by weight of diltiazem or a pharmaceutically acceptable salt or ester thereof. The ratio of hydrophilic polymer to enteric polymer is in the range of about 1:1 to about 15:1. Such a pharmaceutical composition releases diltiazem at a rate that allows effective plasma levels of diltiazem to be maintained over a period of twenty-four hours after administration to human adult subjects.

Abstract: This invention is directed to a novel solid matrixed controlled release, oral dosage form where the dosage form contains a therapeutically effective amount of a sulfonylurea or a salt or derivative thereof in the matrix. Further, the use of an aqueous alkalizing medium affords substantially complete bioavailability of the drug from the matrix of the tablet. The core tablets may optionally be coated with a coating material in the range of 2% to 10% with an enteric material or with a water insoluble material like ethyl cellulose.

Abstract: Disclosed is a process for the preparation of pharmaceutical dosage units containing as an active substance of from 0.005 to 1.0% by weight of micronised Org 30659, comprising (a) a mixing step comprising bringing into association the active substance and a suitable carrier to form a mixture, and (b) a granulating step in which the mixture is granulated to form agglomerates or granules by wetting the mixture with a binder liquid, the wetting being conducted under agitation, characterised in that the granulation step (b) is conducted so as to exert on the granules a shear force which does not exceed the tensile strength of the agglomerates or granules. The process leads to granules and tablets having an excellent content/uniformity.

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 sustained release capsule in which an outer surface of a hard capsule mainly composed of gelatin and containing a physiologically active substance is uniformly covered with a film material comprising a natural polysaccharide/polyhydric alcohol composition which is prepared by uniformly kneading at least one natural polysaccharide selected from the group consisting of carrageenan, alginic acid, salts of alginic acid, derivatives of alginic acid, agar, locust bean gum, guar gum, pectin, amylopectin, xanthane gum, glucomannan, chitin and pullulan in at least one system selected from the group consisting of polyhydric alcohols, sugar alcohols, monosaccharides, disaccharides, trisaccharides and oligosaccharides. A capsule formed merely of the natural polysaccharide/polyhydric alcohol composition swells and is permeated by water. It is poor in shape-retaining properties, failing to retain its shape in the stomach, although it is nondigestive.

Abstract: Described herein is a particular type of pharmaceutical tablet, for oral use, which is formed by one or more layers, and is specifically designed for controlled release of active principles that present problems of bio-availability linked to absorption in the gastro-intestinal tract, and in particular active principles that present an erratic and unpredictable absorption linked to the presence or absence of food at the level of the stomach and/or of the first portion of the small intestine, the said pharmaceutical form being characterized in that it is completely coated with one or more films of a biocompatible and biodegradable polymeric material.

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: 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: An improved method for the treatment of central nervous system disorders comprises treating patients with an enteric fluoxetine formulation.

Abstract: Process is provided for preparing an oral solid rapidly disintegrating freeze-dried dosage form of a pharmaceutically active substance having an unacceptable taste, wherein prior to freeze drying, a suspension of uncoated or coated coarse particles of a pharmaceutically active substance in a carrier material is cooled to reduce the viscosity and minimize release of the active substance during processing, as well as beyond the point of disintegration of the form in the mouth, to minimize bad taste from the drug.

Abstract: The present invention provides methods and compositions for slowing gastrointestinal transit and prolonging residence time to optimize presentation and absorption of ingested nutrients and/or pharmacologically active agents in the small intestine to prevent and/or reduce ineffectiveness thereof due to malabsorption.The present invention further provides methods and compositions for enhancing the bioavailability and therapeutic effectiveness of pharmacologically active agents.

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: 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: 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: 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: Disclosed are a variety of compositions and methods for use in specifically targeting the L-selectin or preferably, the E-selectin marker following its cell surface induction, e.g., using ionizing radiation, in tumor vasculature endothelial cells. The compositions and methods described are suitable for use in the delivery of selected agents to tumor vasculature, as may be used in the diagnosis aid therapy of solid tumors.

Abstract: Preparation process for a multiparticulate pharmaceutical form with a plurality of sequences of controlled release of the type which allows the body of the patient to be provided with a sufficient concentration of one or more active ingredients by one or two administration over 24 hours.

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: An oral pharmaceutical preparation containing a therapeutically effective amount of a salt of morphine for administration once daily is provided. The preparation contains particles which have a core containing a salt of morphine coated with a barrier layer. The barrier layer is formed from a coating liquid that contains at least one water insoluble barrier forming component selected from the group consisting of ethyl cellulose, copolymers of acrylic and methacrylic esters and natural or synthetic waxes, and a plasticizer. The mean serum concentration of morphine obtained is at least 50% of the maximum serum concentration during at least 12 hours after the administration of a single dose of the preparation.

Abstract: The invention relates to sustained release formulations comprising 11-?4-?2-(2-hydroxyethoxy)ethyl!-1-piperazinyl!dibenzo?b,f! ?1,4!thiazepine or a pharmaceutically acceptable salt thereof, to methods of treating psychotic states and hyperactivity utilizing the sustained release formulations and to a process for preparing the sustained release formulations.

Abstract: The present disclosure relates to novel dosage forms, drug delivery regimens, methods and pharmaceutical compositions which optimize the therapeutic effects of active therapeutic substances through the application of the concept of uneven dosing.

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: A superior enteric formulation of the antidepressant drug, fluoxetine, is in the form of enteric pellets of which the enteric layer comprises hydroxypropylmethylcellulose acetate succinate.

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 delivery device for delivering an active substance to a patient at a predetermined time after administration comprises a male hydrogel plug engaged in the neck of a female body. An expandable excipient such as a hydrogel powder or a pharmaceutical disintegrant in powder, slug or tablet form is provided beneath the active substance. In contact with an aqueous medium, the excipient absorbs water and swells such as to rapidly expel the active substance and effectively deliver it from the device.

Abstract: A process for the manufacture of particles comprises mechanically working a mixture of a drug and a hydrophobic and/or hydrophilic fusible carrier in a high speed mixture so as to form agglomerates, breaking the agglomerates to give controlled release particles and optionally continuing the mechanical working with the optional addition of a low percentage of the carrier or diluent.

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: There are provided a seamless capsule containing therein a large quantity of an active ingredient which is difficultly soluble in water and oil and a method of manufacturing the seamless capsule. Encapsulating liquid 1, in which the active ingredient is difficultly soluble in water and oil is suspended in oil as particles each having the mean particle diameter of less than 20 .mu.m, is enclosed in hydrophilic outer shells. This seamless capsule SC is manufactured in such a manner that from a multiple nozzle 7, suspension, in which the active ingredient which is difficultly soluble in water and oil is dispersed in oil and the active ingredient in thus obtained dispersion is pulverized to obtain particles each having the mean particle diameter of less than 20 .mu.m, as encapsulating liquid 1, and aqueous liquid of a shell forming substance, as outer shell forming liquid 3, are dropped into hardening liquid 10.

Abstract: An antimicrobial agent comprising allyl isothiocyanate (AIT) packaged in a packaging material having a structure wherein part of the pores of a porous packaging substrate is filled with, or said pores are partially or entirely narrowed by a resin impervious to AIT vapor, and a method for controlling the AIT vapor release speed comprising enclosing AIT in the above-mentioned packaging material. According to the present invention, the AIT vapor release speed can be controlled, whereby enabling sustained release of AIT vapor and persistent effect of antimicrobial action. In addition, the antimicrobial agent of the present invention can be widely applied to food industries and various other fields where breeding and reproduction of deleterious microorganisms pose problems, since it is economical, compact and easy to use.

Abstract: Methods are provided for the treatment of a host suffering from a cellular proliferative disease through administration of a chemotherapeutic agent in conjunction with a cell membrane permeant. Optionally, the cell membrane permeant and/or chemotherapeutic agent will be present in a pharmaceutically acceptable vehicle capable of acting as a depot. In the subject methods, the chemotherapeutic agent and membrane permeant are administered at least proximal to a target site of the host. Administration of chemotherapeutic agents in accordance with the subject methods results in improved efficacy of, and/or decreased host toxicity to, the intralesionally administered chemotherapeutic agent.