Abstract: The invention relates to a matrix tablet for the prolonged release of gliclazide which ensures continuous and consistent release of the active ingredient after administration by the oral route, the release being insensitive to variations in the pH of the dissolution medium.

Abstract: The invention is concerned with a novel process for the manufacture of flowable, non-dusty, binder-free riboflavin granulates by subjecting an aqueous suspension of riboflavin crystals of crystal modification B/C to a fluidized bed spray drying process, a single fluid nozzle spray drying process or a disk-type spray drying process.

Abstract: A new oral polymeric controlled release formulation suitable for the once-a-day administration of valproate compounds, such as divalproex sodium, has been discovered. This formulation exhibits significant advantages over the sustained release valproate formulations of the prior art. This formulation minimizes the variation between peak and trough plasma levels of valproate over a 24 hour dosing period. This formulation follows a zero-order release pattern thus producing essentially flat plasma levels of valproate, once steady-state levels have been achieved. This results in a significantly lower incidence of side effects for patients consuming such a formulation.

Abstract: A process for increasing the percentage of active ingredient relative to non-active excipient in a compressible formulation, and also for reducing tablet size, by excluding an amount of the excipient and including in its place a reduced amount of a polysaccharide material.

Abstract: There is provided an orally deliverable pharmaceutical composition comprising a selective cyclooxygenase-2 inhibitory drug of low water solubility such as celecoxib and a release-extending polymer. The composition is useful in treatment of cyclooxygenase-2 mediated conditions and disorders by once-a-day administration.

Abstract: This invention relates to a controlled or sustained release formulation designed to deliver a PDE4 inhibitor for treating an inflammatory disease such as asthma or COPD and the like.

Abstract: A new oral polymeric controlled release formulation suitable for the once-a-day administration of valproate compounds, such as divalproex sodium, has been discovered. This formulation exhibits significant advantages over the sustained release valproate formulations of the prior art. This formulation minimizes the variation between peak and trough plasma levels of valproate over a 24 hour dosing period. This formulation follows a zero-order release pattern thus producing essentially flat plasma levels of valproate, once steady-state levels have been achieved. This results in a significantly lower incidence of side effects for patients consuming such a formulation.

Abstract: A zero-order release pharmaceutical dosage form for oral administration to a patient comprising a core tablet sheathed in an annular body of compressed powder or granular material is provided. A preferred embodiment of the zero-order release pharmaceutical dosage form is a solid pharmaceutical dosage form which reduces contact of the active ingredient in solid form with the mucosa lining the gastrointestinal tract, which is particularly advantageous for delivering an ulcerative drug. A process for making the zero-order release pharmaceutical dosage form are also provided.

Abstract: The invention relates to an oral pharmaceutical composition which has excellent drug release-controlling ability in the mouth even 5 to 10 minutes after its administration and also has excellent drug releasing ability in the digestive tract without using capsules. It also relates to an oral pharmaceutical composition which comprises one or more drugs having a bitter taste, one or more solid proteins, and one or more pharmaceutically acceptable polymer bases, wherein the proteins are present in the polymer bases preferably as particles.

Abstract: Hypnotic pharmaceutical compositions are made from pellets and exhibit a modified release. Zolpidem or a pharmaceutically acceptable salt thereof is a typical hypnotic. The pellets are preferably spherical and exhibit a dissolution profile that includes 60% of the hypnotic agent being release from the pellet not earlier than 5 minutes from the start of a specified in vitro dissolution test. Although the modified release profile can include 50% of the hypnotic agent being released not earlier than 15 minutes after the start of the dissolution test, the pellet preferably does not contain a release rate controlling excipient or coating. Instead, microcrystalline cellulose and the active constitute the majority of the pellet, e.g. 90% or more. Spherical pellets are also made by a convenient method that is applicable to any pharmaceutically active agent.

Abstract: The present invention relates to a novel spray drying process for the preparation of pharmaceutical compositions containing small particles of phospholipid-stabilized fenofibrate. This invention also relates to spray dried powdered compositions prepared according to this process, and to dosage forms of fenofibrate (capsules, tablets, powders, granules, and dispersions) prepared from these powdered compositions. The powdered compositions and dosage forms are useful in the treatment of dyslipidemia and dyslipoproteinemia and have the advantage that they provide reduced in vivo variability in the bioavailability of fenofibrate active species among fed and fasted patients when administered orally.

Abstract: The present invention discloses an efficient preparation method of spherical fine particles containing a drug for an easily-swallowed, controlled-release preparation comprising the production of drug-containing spherical fine particles (mean particle size: 60-200 &mgr;m) by adding a binder solution to a mixture containing an excipient powder having the property of retaining solvent (and preferably having a mean length of the long axis of 40 &mgr;m or less) and a drug powder (preferably having a mean length of the long axis of 50 &mgr;m or less), followed by high-speed mixing granulation.

Abstract: Pharmaceutical compositions of bisphosphonic acids, and salts thereof, are prepared by wet granulation tablet formulation. These pharmaceutical compositions are useful in the treatment of disturbances involving calcium or phosphate metabolism, in particular, the treatment and prevention of diseases involving bone resorption, especially osteoporosis, Paget's disease, malignant hypercalcemia, and metastatic bone disease. These compositions are prepared without the addition of binder; instead, the drug itself acts as a binder.

Abstract: This invention relates to the field of chemical pharmaceutical industry, namely, to pharmaceutical formulations for preparation of prolonged release tablets, in particular, tablets for sublingual application, and to methods of preparation of such formulations. Pharmaceutical formulation comprises 96.0 to 99.8% wt. of the pharmaceutical drug microcapsules, 0.1 to 1% wt. of lubricant, and 0.1 to 3% wt. of water, each microcapsule comprising 96.0 to 99.2% wt. of the pharmaceutical drug and 0.8 to 4% wt. of film-forming substance. Dispersant is also introduced into formulation in the amount of 0.1 to 10% wt. of the total mixture obtained. Method of preparation of the pharmaceutical formulation comprises preparation of microcapsules by deposition of coating of film-forming substance on non-agglomerated particles of pharmaceutical drug, and addition of lubricant and dispersant.

Abstract: Sustained release dosage forms of high dose insoluble drugs such as ibuprofen and methods for their manufacture are disclosed.

Abstract: Novel administration form for acid-labile active compounds are described. The novel administration forms have no enteric layers and are suitable for oral administration.

Abstract: A method is disclosed for manufacturing a pharmaceutical tablet for oral administration, the tablet combining both immediate-release and prolonged-release modes of drug delivery and using an immediate-release drug that is either insoluble in water or only sparingly soluble and is present in a very small amount compared to the prolonged-release drug. The method involves the use of particles of the immediate-release drug that are equal to or less than 10 microns in diameter, applied as a layer or coating over a core of the prolonged-release drug, the layer or coating being either the drug particles themselves, applied as an aqueous suspension, or a solid mixture containing the drug in admixture with a material that disintegrates rapidly in gastric fluid.

Abstract: The dry blends comprise a powdery or finely-divided active ingredient such as a pharmaceutical, dietary supplement, agricultural chemical, water-treating agent or biocidal agent, and a micronized synthetic polyolefin-based hydrocarbon wax and/or a micronized synthetic polyfluorocarbon wax that is compatible with the active ingredient. Shape-retentive compacted compositions are formed by pressure compacting such blends. Preferred active ingredients are 1,3-dihalo-5,5-dialkylhydantoins and profen pharmaceuticals such as naproxen.

Abstract: There is disclose a rate controlled delivery system for a beta-blocker form by extruding a blend of the beta-blocker, a filler, a binder/defoamer and a blend of polymers which have been intimately mixed in a densification and extrusion molding to provide a quasi-monolithic compact mass which erodes over a period of from 12 to 16 hours thereby to provide therapeutic performance for a period of 24 hours.

Abstract: Methods for reducing flushing in individuals being treated for hyperlipidemia with nicotinic acid are disclosed. According to the methods of the present invention, flushing can be reduced in individuals under going nicotinic acid therapy without causing drug-induced hepatotoxicity to a level that would require the nicotinic acid therapy to be discontinued by orally administering to the individuals intermediate nicotinic acid formualtions having unique biopharmaceutical characteristics as a single dose once per day. While the methods of the present invention contemplate administering the intermediate release nicotinic acid formulations at any time during a 24 hour period, it is preferable to administer them once-a-day as a single dose during the evening or at night between about 6:00 pm. and 12:00 a.m., preferably between about 8:00 p.m. and 12:00 a.m., and most preferably between about 8:00 p.m. and 10:00 p.m.

Abstract: A device for controlled release of pharmaceutical agents and a method for use of the device. The drug delivery device comprises a covered container with an aperture and an aperture cover, containing a pharmaceutical agent and an excipient formulation.

Abstract: A method and controlled release oral unit dosage form of acetylsalicylic acid (aspirin) delays the release of the drug until a predetermined time interval after ingestion. This enables the drug to reach optimal therapeutic blood levels at a time in the early morning when the events leading up to a vascular obstruction culminating in a heart attack or stroke are most commonly occurring after the drug is taken in the evening. The convenience of taking the drug every evening should enhance compliance. By arranging for the optimal blood level to coincide with the peak incidence of strokes, a much smaller total dose of the drug may be used than is normally prescribed. This may reduce the incidence of side effects that are dose related. This will make the prophylactic use of aspirin available to more of the population.

Abstract: The present invention provides storage stable, shaped particles of allotropic organic compounds. The particles of the present invention can be shaped according to the desired application. Preferred shapes of such particles are microspheres, particularly those having diameters of about 1 to about 1,000 microns. The stable shaped particles of the present invention are particularly well-suited to the fabrication of pharmaceutical formulations, particularly where sustained release and uniform bioavailability are desired. The storage stable particles are formed by a solid state crystallization of allotropic organic compounds. The solid state crystallization process of the present invention affords a means for achieving a storage stable crystalline form of said allotropic compound without loss or deterioration of the original particle dimensions.

Abstract: A biphasic controlled release delivery system for pharmaceuticals which have high water solubility, such as the antidiabetic metformin HCl salt, is provided which provides a dosage form that has prolonged gastric residence so that a dosing regimen of at least one gram metformin, once daily, may be achieved while providing effective control of plasma glucose.

Abstract: Bacterial infections may be treated using a high dosage regimen of amoxycillin. Preferably, the dosage is provided by a bilayer tablet.

Abstract: The present invention discloses a process for preparing controlled-release preparations which can rapidly release 99% or more of a slightly soluble medicament (which has by itself shows a slow dissolution rate) in the upper part of the small intestine and compositions thereof. The present invention also discloses a process comprising carrying a slightly soluble medicament which has a slow intestinal dissolution rate on aggregates of the spherical microparticles of a multivalent metal alginate, in which each of the secondary particles (i.e., the aggregates) has a specific surface area ranging from 1 to 280 m2/g and compositions thereof.

Abstract: Dosage forms comprising pulse release formulations 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: The present invention provides storage stable, shaped particles of allotropic organic compounds. The particles of the present invention can be shaped according to the desired application. Preferred shapes of such particles are microspheres, particularly those having diameters of about 1 to about 1,000 microns. The stable shaped particles of the present invention are particularly well-suited to the fabrication of pharmaceutical formulations, particularly where sustained release and uniform bioavailability are desired. The storage stable particles are formed by a solid state crystallization of allotropic organic compounds. The solid state crystallization process of the present invention affords a means for achieving a storage stable crystalline form of said allotropic compound without loss or deterioration of the original particle dimensions.

Abstract: The present invention relates to oral dosage forms comprising a) one or more active ingredients b) a formulated mixture of polyvinyl acetate and polyvinylpyrrolidone c) where appropriate other excipients customary for producing the dosage form, wherein they float on gastric fluid and display delayed release of active ingredient, and to the use and production thereof.

Abstract: The present invention relates to a method of forming non-dihydrate azithromycin granules, comprising mixing non-dihydrate azithromycin particles, with a granulating amount of a granulating liquid, and, optionally, with one or more excipients, to form wet granules which comprise non-dihydrate azithromycin and the granulating liquid. The granules are then dried to remove the granulating liquid.

Abstract: A chronotherapeutic pharmaceutical formulation comprising a core containing an active agent (e.g., a drug) and a delayed release compression coating comprising a natural or synthetic gum applied onto the surface of the core.

Abstract: A multi-stage oral drug controlled-release system is disclosed, as well as a preparation for maintaining the drug blood concentration at a desired level for a prolonged time. The system operates by releasing the drug at a constant rate through stepwise control of drug release following administration of the preparation. More specifically, the multi-stage oral drug controlled-release system involves the stepwise release of drug-containing granules from an inner matrix, which is surrounded by a coating or release-modifying layer. The granules contain an active drug and a carrier material in size of 0.1˜1 mm. The carrier material is hydrophobic when the drug has a water-solubility of 1 mg/ml or more, and is hydrophilic when the drug has a water-solubility of less than 1 mg/ml. The inner matrix, in which the drug-containing granules are embedded, is formed from swelling and erodible polymer(s) and swelling-regulating material(s).

Abstract: Solid dosage articles such as pharmaceutical tablets for the controlled release of a desired compound such as an active ingredient are directly compressed from a flowable, compressible mixture of the active ingredient, a slightly cross-linked rheology modifying polymer or copolymer, and one or more excipients. The rheology modifying polymer or copolymer is a granulated powder of suitable particle size and is generally made from one or more unsaturated (di)carboxylic acids, half ester thereof, and other optional monomers.

Abstract: Provided is a slow-release delivery vehicle for delivering at least one active ingredient into a film coating, comprising a population of stable, homogeneously-dispersed, porous polymeric or co-polymeric beads having a network of pores, wherein the at least one active ingredient is held within the bead particles and within the network of pores and slowly released by internal flow, and wherein the network of pores is substantially non-collapsible upon removal of the active ingredient. The porous co-polymer bead preparation comprises a continuous aqueous phase solution containing a monomeric mixture of at least one polyvinylaromatic monomer and at least one porogen forming a network that comprising (i) macropores; (ii) mesopores; (iii) micropores; and (iv) gel porosity. Also provided are methods of preparing the porous co-polymer bead preparation; and for its use as a slow-release delivery vehicle.

Abstract: There is disclosed a method for stabilizing active substances that are unstable in acidic medium, unstable when stored for longer periods of time in the presence of water and at the same time sensitive to heating, by means of anhydrous granulation of active substances and dried pharmaceutically acceptable auxiliary substances for the preparation of pellet cores or granules. All pharmaceutically acceptable auxiliary substances employed are dried before use so that their weight loss at drying is less than 1.0% of the total weight of the pharmaceutically acceptable auxiliary substance, preferably less than 0.5%. Organic solvents used in process of anhydrous granulation should contain less than 0.2% of water. A novel pharmaceutical formulation with controlled release of active substances that are unstable in acidic medium, unstable when stored for longer periods of time in the presence of water and at the same time sensitive to heating, is disclosed as well.

Abstract: The new galenic formulation of paracetamol is comprised of a base mixture of paracetamol and citric acid in a proportion of 85:15 to 90:10 w/w among other pharmaceutically acceptable components, in an exsiccation state corresponding to a water activity of less than 0.6 and it is in the form of a powder, granulate or tablet. The process comprises obtaining said exsiccated base mixture up to a water activity of less than 0.6 in order to obtain a powder, that can be granulated in order to obtain a granulate dispersible and soluble in water, whose granulate can also be compressed in order to obtain a tablet dispersible and soluble in water. Said new formulation is useful in human and veterinary medicine.

Abstract: A pharmaceutical preparation adopted for sustained release of an active agent(s) over an extended period of time at a therapeutic rate without an initial burst release of the agent(s) upon administration, wherein the preparation comprises: (i) an outer portion prepared from one or more layers of a biodegradable polymer, which is selected to release an active agent over an extended period of time when positioned in situ in a patient, and (ii) an inner portion comprising a plurality of micro-capsules formed from at least a biodegradable polymer, said micro capsules containing at least an active agent, wherein the micro-capsules are compressed into the form of a tablet under suitable pressure to suppress the rate of release of the active agent from the micro-capsules.

Abstract: The invention provides for an enhanced absorption pharmaceutical composition comprising a plurality of microparticles, each microparticle comprising at least one sedative non-benzodiazepine, at least one spheronization aid and at least one solubility enhancer. The microparticles of the invention are further incorporated into an oral fast-dispersing dosage form.

Abstract: A process for preparing divalproex sodium tablets is provided. The process comprises preparing a neutralized divalproex sodium solution by combining divalproex sodium, having a sodium valproate and a valproic acid moiety, with an aqueous solvent and a base, e.g., sodium hydroxide, the base being in sufficient amount to ensure neutralization of the valproic acid moiety of the divalproex sodium. The neutralized divalproex sodium solution is sprayed onto a pharmaceutically acceptable carrier, and processed to obtain divalproex sodium tablets.

Abstract: The invention relates to a multiparticulate drug form suitable for uniform release of an active pharmaceutical ingredient in the small intestine and in the large intestine, comprising at least two forms of pellets A and B which comprise an active pharmaceutical ingredient in the core and have different polymer coatings which determine the release of the active ingredient at different pH values, characterized in that pellet form A is provided with an inner polymer coating which enables continuous release of active ingredient, and has an outer enteric coating which rapidly dissolves above about pH 5.5, and pellet form B is provided with a polymer coating which, in the USP release test, releases less than 20% of the active ingredient at pH 6.8 in 6 hours and releases more than 50% of the active ingredient at pH 7.2 in 6 hours. The invention additionally relates to a process for producing the multiparticulate drug form and to the use of pellet forms A and B for producing the drug form.

Abstract: A multiple pulsed dose drug delivery system for pharmaceutically active amphetamine salts, comprising an immediate-release component and an enteric delayed-release component wherein (1) the enteric release coating has a defined minimum thickness and/or (2) there is a protective layer between the pharmaceutically active amphetamine salt and the enteric release coating and/or (3) there is a protective layer over the enteric release coating. The product can be composed of either one or a number of beads in a dosage form, including either capsule, tablet, or sachet method for administering the beads.

Abstract: An enteric coated pharmaceutical extended release dosage form of a H+, K+-ATPase inhibitor giving an extended plasma concentration profile of a H+, K+-ATPase inhibitor. The extended plasma profile is obtained by a pharmaceutical composition which comprises a core material of a hydrophilic or hydrophobic matrix, and the H+, K+-ATPase inhibitor and optionally pharmaceutically acceptable excipients. The dosage form may be administered once daily.

Abstract: The present invention relates to a controlled release system useful for site specific delivery of biologically active ingredients or sensory markers, over an extended period of time, targeting biological surfaces comprising the oral cavity and mucous membranes of various tissues, as well as the controlled release of the biological active ingredients or sensory markers. The controlled release system of the present invention is a nano-particle, having an average particle diameter of from about 0.01 microns to about 10 microns, which comprises a biodegradable solid hydrophobic core and a bioadhesive/mucoadhesive positively charged surface. The invention also relates to the use of the nano-particles of the present invention in consumer oral hygiene products, such as toothpaste or mouthwash, for treatment and prevention of periodontal disease. The nano-particles of the present invention are particularly effective for targeted controlled delivery of biological active ingredients into the periodontal pocket.

Abstract: A test system for characterizing the compatibility of bioactive substances with polyvinylpyrrolidones in a solid dispersion consisting of one or more bioactive substances and 1,3-bis(1-pyrrolidonyl)butane.

Abstract: An oral pharmaceutical modified release multiple-units composition for the administration of a therapeutically and/or prophylactically effective amount of a non-steroid anti-inflammatory drug substance to obtain both a relatively fast onset of the therapeutic effect and the maintenance of a therapeutically active plasma concentration for a relatively long period of time is disclosed.

Abstract: Provided herein are compositions and methods of making compositions of ibuprofen in combination with a narcotic analgesic. Specifically provided is a pharmaceutical tablet composition comprising ibuprofen; a narcotic analgesic; colloidal silicon dioxide; a filler selected from the group consisting of microcrystalline cellulose and powdered cellulose; a disintegrant selected from the group consisting of croscarmellose sodium, crospovidone, and sodium starch glycolate; a binder consisting of an akylhydroxy methylcellulose; a starch; and a lubricant.

Abstract: This invention provides a formulation for preparing a fast disintegrating tablet comprising a drug in multiparticulate form, one or more water insoluble inorganic excipients, one or more disintegrants, and optionally one or more substantially water soluble excipients, the amounts of said ingredients being such as to provide a disintegration time for the tablet in the order of 75 seconds or less, typically 30 seconds or less.

Abstract: Sustained release formulations of oxymorphone or pharmaceutically acceptable salts thereof; methods for making the sustained release formulations of oxymorphone or pharmaceutically acceptable salts thereof; and methods for using the sustained release formulations of oxymorphone or pharmaceutically acceptable salts thereof to treat patients suffering from pain are provided.

Abstract: The present invention is directed to an oral dosage form for multiple-pulsed delivery of at least two fractions of clindamycin to a subject, one in an immediate-release form and the other in an extended release form. The oral dosage forms of the present invention provide a means for treating or preventing gram-positive bacterial infections with a minimal number of treatments per day, potentially, as little as once or twice per day.

Abstract: The invention relates to a multiparticulate modified release composition that in operation delivers an active ingredient in a pulsed or bimodal manner. The multiparticulate modified release composition comprises an immediate release component and a modified release component; the immediate release component comprising a first population of active ingredient containing particles and the modified release component compnsimg a second population of active ingredient containing particles coated with a controlled release coating; wherein the combination of the immediate release and modified release components in operation deliver the active ingredient in a pulsed or a bimodal manner. The invention also relates to a solid oral dosage form containing such a multiparticulate modified release composition.