Abstract: A new soft gelatine formulation and process methodology is disclosed herein that increases single Coenzyme Q10 molecules presented to the absorption channels of the small intestines by providing medium chain triglycerides, Vitamin E, and natural beta carotene to Coenzyme Q10 in a soft gel capsule to increase the absorption thereof.

Abstract: Film coatings for enteric and colonic release at selected pH are provided by selecting and/or formulating a shellac of a predetermined acid number. The method includes the selection of the acid number to provide the release at the specified pH and a method of providing a shellac of a predetermined acid number by blending of shellacs of different acid numbers. In general, films that release or dissolve at or above pH 7.4 are based on the selection of shellac with an acid number below 74. Films that release or dissolve above pH 7.0 are comprised of shellac selected with an acid number below 80. Films that release or dissolve at below pH 7.0 are comprised of shellac selected to have an acid number above 80. The film coating may be modified with a water soluble resin and/or a plasticizer. Preferably the shellac will comprise 50% or more of the resin system, and is formed out of water, not alcohol.

Abstract: A once a day bupropion hydrochloride formulation is disclosed.

Abstract: The invention provides fenofibrate compositions comprising granulates. The granulates can comprise micronized fenofibrate, inert hydrosoluble carrier particles, hydrophilic polymers, and, optionally, surfactants.

Abstract: Novel pharmaceutical dosage forms provide for pulsatile delivery of methylphenidate, i.e., release encapsulated drug in spaced apart “pulses.” The dosage forms are comprised of first, second and optionally third dosage units, with each dosage unit having a different drug release profile. The dosage forms may comprise capsules housing compressed tablets or drug-containing beads or particles, or may comprise a single tablet with the first, second and optionally third dosage units each representing an integral and discrete segment thereof. Methods of treatment using the pharmaceutical dosage forms are provided as well.

Abstract: The present invention provides exemplary systems and methods for producing dry powder formulations. In one embodiment, a system (10) includes at least one conditioning zone (12) having an inlet (20) to introduce an atomized formulation (18) into the conditioning zone. A controller (14, 16) controls temperature and relative humidity of the airflow into the conditioning zone to allow amorphous-to-crystalline transformation of the atomized formulation. In another embodiment, the formulation is suspended in the conditioning zone for a residence time of sufficient duration to allow surface orientation of surface active components. A dryer (24) is coupled to the conditioning zone to dry the atomized formulation, and a collector (28) collects the formulation in powder form.

Abstract: The subject of the present invention is a process for preparing pregelatinized high amylose starch, comprising the steps consisting of:

Abstract: Methods of and apparatus for preparing temperature activated gaseous precursor-filled liposomes are described. Gaseous precursor-filled liposomes prepared by these methods are particularly useful, for example, in ultrasonic imaging applications and in therapeutic drug delivery systems.

Abstract: Oral dosage forms are provided for the administration of a bisphosphonic acid compound in the prevention and treatment of conditions involving calcium or phosphate metabolism, i.e., conditions associated with bone resorption such as osteoporosis, Paget's disease, periprosthetic bone loss, osteolysis, malignant hypercalcemia, metastatic bone disease, multiple myeloma, and periodontal disease. The dosage forms are either enterically coated capsules housing the drug in a liquid or semi-solid carrier, or enterically coated osmotically activated drug delivery devices.

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: A method of producing a free flowing and compressible liquid/power admixture of an active drug substance, by converting the active substance into a liquisolid system. This is accomplished by introducing by the drug into a non-volatile liquid or a mixture of non-volatile and volatile liquids to from a mixture, selecting at least one solid carrier material and admixing these components to produce a non-adherent, free-flowing and compressible liquid/power mass admixture, the amounts of drug and carrier being selected to optimize flow and compressibility.

Abstract: A sustained releasing drug which includes an effective component and a copolymer having a weight-average molecular weight of 1,000 to 100,000 which comprises, as repeating structure units, both of a succinimide unit represented by the structural formula (1) and a hydroxycarboxylic acid unit represented by the structural formula (2) wherein R is a methyl group or a hydrogen atom, and a process for preparing a copolymer which comprises a polymerization step of heating a mixture of aspartic acid and a cyclic ester compound.

Abstract: The invention relates to medicaments for initiating ovulation comprising LH in an administrable form which ensures an increase in LH plasma levels for a period of some 40 to 60 hours.

Abstract: This invention relates to a 24 hour extended release dosage formulation and unit dosage form thereof of venlafaxine hydrochloride, an antidepressant, which provides better control of blood plasma levels than conventional tablet formulations which must be administered two or more times a day and fiber provides a lower incidence of nausea and vomiting than the conventional tablets. More particularly, the invention comprises an extended release formulation of venlafaxine hydrochloride comprising a therapeutically effective amount of venlafaxine hydrochloride in spheroids comprised of venlafaxine hydrochloride, microcrystalline cellulose and, optionally, hydroxypropylmethylcellulose coated with a mixture of ethyl cellulose and hydroxypropylmethylcellulose.

Abstract: Pharmaceutical capsule dosage forms of benzimidazole proton pump inhibitors are prepared by enclosing one or several enteric coated compressed cores in a capsule shell. The inventive formulations are stable and have higher bioavailability of the active ingredient relative to pellet and granule containing formulations.

Abstract: Novel forms of sustained-release microgranules (LP) containing diltiazem are disclosed. The microgranules consist of a neutral granular carrier coated with an active layer including diltiazem or a pharmaceutically acceptable salt thereof as the active principle, a surfactant and a binder, and an outer layer providing sustained release of the active principle (layer LP).

Abstract: A preservative for emulsion, comprising sorbic acid or a pharmaceutically acceptable salt thereof, and, where necessary, sodium edetate and boric acid; an emulsion comprising sorbic acid or a pharmaceutically acceptable salt thereof, and, where necessary, sodium edetate and boric acid; an emulsion comprising the preservative; a method for preserving an emulsion comprising adding sorbic acid or a pharmaceutically acceptable salt thereof, and, where necessary, sodium edetate and boric acid, at a concentration pharmaceutically acceptable and effective for the preservation of the emulsion; use of sorbic acid or a pharmaceutically acceptable salt thereof for the production of an emulsion or preservative for emulsion; and the use comprising adding, where necessary, sodium edetate and boric acid.

Abstract: A novel extended or controlled release encapsulated product is provided and includes: at least one active ingredient; at least one erodible polymer; and at least one lubricating material; wherein the encapsulated product is in the form of a caplet having a diameter of from about 1 millimeter to about 7 millimeters and a length from about 1 millimeter to about 7 millimeters. A method for preparing the encapsulated product is also provided.

Abstract: A pharmaceutical MR (modified release) multiparticulate dosage form such as a capsule (once-a-day MR Capsule) of Methylphenidate indicated for the treatment of children with attention deficit hyperactivity disorder (ADHD), capable of delivering a portion of the dose for rapid onset of action and the remainder of the dose in a controlled manner for about 12 hours, is composed of a multitude of multicoated particles made of two populations of drug layered beads, IR (immediate release) and ER (extended release) Beads. The IR beads preferably are made by layering an aqueous solution comprising a drug and a binder on to non-pareil sugar spheres and then applying a seal coat to the drug coated cores. The ER Beads are made by applying an extended release coating of a water insoluble dissolution rate controlling polymer such as ethylcellulose to IR Beads.

Abstract: Novel pharmaceutical dosage forms provide for pulsatile delivery of methylphenidate, i.e., release encapsulated drug in spaced apart “pulses.” The dosage forms are comprised of first, second and optionally third dosage units, with each dosage unit having a different drug release profile. The dosage forms may comprise capsules housing compressed tablets or drug-containing beads or particles, or may comprise a single tablet with the first, second and optionally third dosage units each representing an integral and discrete segment thereof. Methods of treatment using the pharmaceutical dosage forms are provided as well.

Abstract: The invention is related to a solid sustained release once-a-day oral dosage form comprising hydromorphone or a pharmaceutically acceptable salt thereof together with a sustained release carrier, the dosage providing a relatively rapid rise in plasma concentration to an initial early peak concentration, followed by a second broader peak with plateau plasma concentrations.

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: 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: A colonic drug delivery composition is provided and comprises a starch capsule containing a drug, the starch capsule being provided with a coating such that the drug will only be released from the capsule in the colon. The coating may be a pH sensitive material, a redox sensitive material, or a material broken down by specific enzymes or bacteria present in the colon. The drug to be delivered may be one for local action in the colon or a systemically active drug to be absorbed from the colon.

Abstract: The invention provides a micronized fenofibrate composition. The micronized fenofibrate composition has a dissolution of at least 10% in 5 minutes, 20% in 10 minutes, 50% in 20 minutes and 75% in 30 minutes, as measured using the rotating blade method at 75 rpm according to the European Pharmacopoeia, in a dissolution medium constituted by water with 2% by weight polysorbate 80 or with 0.025M sodium lauryl sulfate. The composition can further comprise hydrophilic polymers, surfactants, hydrosoluble carriers, outer phases or layers, or other pharmaceutically acceptable excipients. The immediate-release fenofibrate composition is preferably in the form of a tablet or in the form of granules inside a capsule.

Abstract: This invention relates to a 24 hour extended release dosage formulation and unit dosage form thereof of venlafaxine hydrochloride, an antidepressant, which provides better control of blood plasma levels than conventional tablet formulations which must be administered two or more times a day and further provides a lower incidence of nausea and vomiting than the conventional tablets. More particularly, the invention comprises an extended release formulation of venlafaxine hydrochloride comprising a therapeutically effective amount of venlafaxine hydrochloride in spheroids comprised of venlafaxine hydrochloride, microcrystalline cellulose and, optionally, hydroxypropylmethylcellulose coated with a mixture of ethyl cellulose and hydroxypropylmethylcellulose.

Abstract: A colonic drug delivery composition is provided and comprises a starch capsule containing a drug, the starch capsule being provided with a coating such that the drug will only be released from the capsule in the colon. The coating may be a pH sensitive material, a redox sensitive material, or a material broken down by specific enzymes or bacteria present in the colon. The drug to be delivered may be one for local action in the colon or a systemically active drug to be absorbed from the colon.

Abstract: Novel forms of sustained-release microgranules (LP) containing diltiazem are disclosed. The microgranules consist of a neutral granular carrier coated with an active layer including diltiazem or a pharmaceutically acceptable salt thereof as the active principle, a surfactant and a binder, and an outer layer providing sustained release of the active principle (layer LP).

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: The invention provides a drug delivery composition for colonic delivery comprising a polar drug, an absorption promoter which (a) comprises a mixture of a fatty acid having 6 to 16 carbon atoms or a salt thereof and a dispersing agent, or (b) comprises a mixture of mono/diglycerides of medium chain fatty acids and a dispersing agent, and means adapted to release the polar drug and absorption promoter in the colon following oral administration. A preferred fatty acid is capric acid or a salt thereof. Colon specific delivery can be achieved by providing the composition in a capsule, tablet or pellet which is coated with a material which dissolves in the small intestine or is degraded by the conditions in the colon.

Abstract: Spontaneously dispersible concentrates capable of forming ultramicroemulsions are described. The concentrates include esters of formula (I) and (II): wherein (a) R1, R3, R4, and R5 each independently represents a C6-22 alkyl, a C6-22 alkenyl or a C6-22 alkapolyene and R2 is glucose:(1,2); (b) R2, R3, R4, and R5 each independently represents a C6-22 alkyl, a C6-22 alkenyl or a C6-22 alkapolyene and R1 is glucose:(1,3); (c) R2, R3, R4, and R5 each independently represents a C6-22 alkyl, a C6-22 alkenyl or a C6-22 alkapolyene and R1 is rhamnose:(1,4); or (d) R2, R3, R4, and R5 each independently represents a C6-22 alkyl, a C6-22 alkenyl or a C6-22 alkapolyene and R1 is rutinose:(1,5); wherein (a) R1, R2, and R4 each independently represents a C6-22 alkyl, a C6-22 alkenyl or a C6-22 alkapolyene and R3 is rhamnose:(11,7); or (b) R2 and R4 each independently represents a C6-22 alkyl, a C6-22 alkenyl or a C6-22 alkapolyene, R1 is methyl, and R3 is rutinose:(11,8).

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: 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: 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 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 use of water-soluble or water-dispersible polyurethanes which consists ofa) 0.1-30% by weight of at least one polyol,b) 20-45% by weight of at least one polyetherpolyol,c) 10-45% by weight of at least one diamine comprising an ionic group,d) 30-50% by weight of at least one polyisocyanate with or withoute) further additives as coatings or binders for pharmaceutical presentations.

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: 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 a 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: 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: Bioavailability of peptide active agents to be administered orally is enhanced by a pharmaceutical composition providing targeted release of the peptide to the intestine by virtue of an acid-resistant protective vehicle which transports components of the invention through the stomach. The composition includes an absorption enhancer and a sufficient amount of a pH-lowering agent to lower local intestinal pH. All components are released together into the intestine with the peptide.

Abstract: Powder coated with a sparingly soluble ultraviolet light absorber which is prepared by a method in which the melted sparingly soluble ultraviolet light absorber and an inorganic or organic powder are mixed while heating and then gradually cooled to coat the surface of said powder with the sparingly soluble ultraviolet light absorber, or by a method in which the sparingly soluble ultraviolet light absorber is adsorbed to or made to coat the surface of the inorganic powder or organic powder using a mechanochemical method. The sparingly soluble ultraviolet light absorber can be blended in a high concentration in the system and blended homogeneously in the base agent. Also, stability over time is superior and the ultraviolet light protection effect is high.

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 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: 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: 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: 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: 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.