Abstract: The invention relates to the use of biodegradable microspheres that release a radiosensitizing anticancer agent for producing a medicament to be used simultaneously with, separately from or spread over time with a radiotherapy, for treating glioblastoma. The use of said biodegradable microspheres according to the invention results in a patient survival time of least 90 weeks, a thereapeutically effective concentration being maintained in the parenchymatous area throughout this time. The microspheres used prefereably contain 5-fluorouracile of the tumor, by intratissular injection. The radiothereapy targeting the tumorous mass is dosed at 60 Gy over approximately 6 weeks. The invention also relates to a method for producing the biodegradable microspheres by emulsion-extraction, and to a suspension containing the biodegradable microspheres obtained using this method.

Abstract: Pharmaceutical compositions that enable the release of a physiologically active substance over a prolonged period of time following administration to a patient are described. The pharmaceutical compositions are provided by encapsulation of a physiologically active substance into a matrix comprising biodegradable polymers and lipids. The rate of release of the physiologically active substance from the pharmaceutical composition is controlled by varying the ratio of the polymer to the lipid. The compositions can be stored in an aqueous suspension or as a solid dosage form. The physiologically active substances include small molecules, peptides, proteins, nucleic acids and vaccines. The biodegradable polymers include homopolymers, or random or block copolymers. The lipids include phospholipids, cholesterol and glycerides.

Abstract: Particles having a tap density less than about 0.4 g/cm3 are formed by spray drying from a colloidal solution including a carboxylic acid or salt thereof, a phospholipid, a divalent salt and a solvent such as an aqueous-organic solvent. The colloidal solution can also include a therapeutic, prophylactic or diagnostic agent. Preferred carboxylic acids include at least two carboxyl groups. Preferred phospholipids include phosphatidylcholines, phosphatidylethanolamines, phosphatidylglycerols, phophstidylserines, phosphatidylinositols and combinations thereof. The particles are suitable for pulmonary delivery.

Abstract: Bioabsorbable biocompatible polymers which provide a good match between their properties and those of certain tissue structures are provided. The bioabsorbable biocompatible polymers can be prepared with tensile strengths, elongation to breaks, and/or tensile modulus (Young's modulus) values of the tissues of the cardiovascular, gastrointestinal, kidney and genitourinary, musculoskeletal, and nervous systems, as well as those of the oral, dental, periodontal, and skin tissues. Methods for processing the bioabsorbable biocompatible polymers into tissue engineering devices are also provided.

Abstract: Optical lenses and methods of preparing the same, in which an active material encapsulated in resin capsules is impregnated in said lens, adjacent an optical surface thereof. The active material may be a coloring material for producing a printed color pattern in the iris or other areas of the lens, or it may be a therapeutic agent.

Abstract: The invention provides methods for treating injuries to one or more internal structures of a subject by administering a drug delivery vehicle to an external surface of the injured structure. The drug delivery vehicle substantially adheres to the site of administration and provides for the release of a bioactive agent that reduces or prevents further injury to the internal structure by disease processes, such as hyperplasia.

Abstract: A lipid or other hydrophobic or amphiphilic compound (collectively referred to herein as “hydrophobic compounds”) is integrated into a polymeric matrix for drug delivery to alter drug release kinetics. In embodiments where the drug is water soluble, the drug is released over longer periods of time as compared to release from the polymeric matrix not incorporating the hydrophobic compound into the polymeric material. In contrast to methods in which a surfactant or lipid is added as an excipient, the hydrophobic compound is actually integrated into the polymeric matrix, thereby modifying the diffusion of water into the microparticle and diffusion of solubilized drug out of the matrix. The integrated hydrophobic compound also prolongs degradation of hydrolytically unstable polymers forming the matrix, further delaying release of encapsulated drug.

Abstract: The present invention relates to pharmaceutical compositions that contain a solid pharmaceutically active compound having a melting point ≧37° C. and a fatty acid or a fatty acid salt or a mixture of a fatty acid and a fatty acid salt. Such composition results in a depression in melting point to ≦37° C. upon contact with an aqueous solution thereby providing an improved outlook for absorption.

Abstract: The present invention provides a composition for enhancing the pharmacological activity of a water-soluble silicate polymer which comprises the water-soluble silicate polymer and a saturated fatty acid in pharmaceutically effective amounts for use as a medicine such as anti-allergic agent. The water soluble silicate polymers used according to the present invention may be obtained by polymerization and/or by extraction from plants, animals or fungi, or inflammatory tissue. The saturated fatty acid contained as an effective ingredient in the pharmaceutical composition of the present invention may be a straight chain or branched chain saturated fatty acid having about 8 carbon atoms to about 26 carbon atoms. The saturated fatty acid and water-soluble silicate polymer, effective ingredients of the present invention, can be formulated for various pharmaceutical compositions by combining with a suitable carrier or diluent for medical use.

Abstract: Formulations for controlled, prolonged release of bioactive molecules such as therapeutic proteins, peptides and oligonucleotides have been developed. These formulations are based on solid microparticles or nanoparticles formed of the combination of biodegradable, synthetic polymers such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), and copolymers thereof. Bioactive molecules are coupled to hydrophilic polymers such as polyethylene glycol or polypropylene glycol and formulated to provide controlled release. The bioactive molecules are more stable, less immunogenic and have improved release rate profiles with lower burst levels and increased drug loading relative to the same bioactive molecules lacking coupled hydrophilic polymers. The controlled release formulations can be administered by injection, by inhalation, nasally, or orally.

Abstract: Disclosed is a process for producing powders from high viscosity fluids including mixing a mixture comprising a high viscosity fluid and at least one absorbing agent until a dry dispersion is produced; combining, under shear, a combination of the dry dispersion with a naturally derived oil having a melting point at least about 110° F.; and granulating the combination into a powder. Also disclosed are pharmaceutical compositions that include a high viscosity fluid, at least one absorbing agent; and a naturally derived oil with a melting point at least about 110° F., together with sustained-release embodiments of such compositions.

Abstract: A care or make-up composition for keratin substances such as the skin, the lips or superficial body growths, this composition containing fibers and particles of an at least partially crosslinked solid elastomeric polyorganosiloxane suspended in an aqueous phase, giving a homogeneous deposit on these keratin substances, while at the same time providing softness and a sensation of freshness; methods of using the composition; and methods of making the composition.

Abstract: Tocopherol derivatives are provided. In one embodiment, the tocopherol derivative includes a tocopherol moiety covalently coupled to branched hydrophilic moiety. In another embodiment, the tocopherol derivative includes a first tocopherol moiety covalently coupled to a second tocopherol moiety through a hydrophilic moiety. In other embodiments, the derivative includes three or more tocopherol moieties.

Abstract: For the preparation of pulverulent particle-reduced formulations with the aid of compressed gases, the solid compound to be formulated, a poorly soluble and usually bioactive active compound, is homogeneously ground together with 10-99% by weight (based on the formulation) of a carrier material which is essentially soluble in the compressed gas mixture, in the presence of compressed gas or mixtures thereof in a stirred autoclave having a mechanical grinding device at process temperatures between 10 and 200° C. and at process pressures between 5 and 500 bar, and in a second process stage the compressed gas mixture, usually dimethyl ether, pure propane and/or carbon dioxide, is expanded by lowering the pressure and separated off from the homogenate, which can also be present as a melt.

Abstract: A stable particle in liquid formulation comprising a discontinuous phase of microparticles is suspended in a continuous phase which is a non-aqueous liquid, preferably biocompatible in which the microparticles are insoluble. The microparticles comprise finely powdered sugar glass, such as trehalose, palatnit, glucopyranosyl sorbitol, glucopyranosyl mannitol, lactitol and monosaccharide alcohols, such as mannitol and inositol, holding at least one biomolecular product, the biomolecular product in the sugar glass either being in stable solid solution or being itself in suspension in the sugar glass.

Abstract: Pharmaceutical dosage units containing flupirtine or a pharmaceutically acceptable salt of flupirtine with controlled release of active substance using a delayed-action or controlled-release component. There are 0.001 to 20 parts delayed-action component for each part by weight flupirtine (calculated as the base) and the release rate of flupirtine is between 5 and 300 mg per hour. In some cases, the dosage units may also contain a rapidly releasing component of flupirtine or of one of its salts. The dosage units reduce the sedative effect of flupirtine.

Abstract: A method of manufacturing an itraconazole oral dosage form that is substantially free of residual methylene chloride comprises the steps of: (a) providing a working solution comprising an alcohol, a strong acid (preferably an inorganic acid or organic sulphonic acid), itraconazole, a water-soluble polymer, and water, with the itraconazole and the strong acid preferably present in the working solution in a ratio of 1 Mole itraconazole to 1-3 Moles acid; (b) providing particles formed from a pharmaceutically acceptable core material; (c) combining the working solution with the particles to produce itraconazole-coated particles; (d) drying the itraconazole-coated particles; and (e) forming the dried itraconazole-coated particles into an itraconazole oral dosage form that is substantially free of residual methylene chloride. The products of such methods and methods of use thereof are also disclosed.

Abstract: Nanoparticulate amorphous cyclosporine formulations, and nanoparticulate cyclosporine formulations comprising a mixture of amorphous and crystalline cyclosporine, having effective average particle sizes of less than about 2000 nm are described. The compositions exhibit increased bioavailability and increased consistency of bioavailability as compared to prior macro-sized cyclosporine and formulations. Methods of making and using the compositions are also described.

Abstract: The present invention includes a cosmetic formulation. The cosmetic formulation comprises a plurality of spheres having a first desiccated volume and having a second hydrated volume. The hydrated volume is greater than the desiccated volume.

Abstract: This invention provides a storage-stable dosage form of a thyroxine active drug composition which exhibits an improved stability. The formulation contains a thyroxine active drug substance, an alditol, and a saccharide, and, optionally, additional pharmaceutically accepted excipients. Levothyroxine sodium is the preferred active drug substance, mannitol is the preferred alditol, and sucrose is the preferred saccharide. Additional preferred excipients include, for example, microcrystalline cellulose, crospovidone, magnesium stearate, colloidal silicon dioxide, and sodium lauryl sulfate.

Abstract: A composition including a hydraulic cement for implantation in a human or animal body. The hydraulic cement includes a first component, a second component, and a third component. The first component includes a calcium source while the second component includes water. The third component is a hydrophobic liquid. The composition hardens after mixing of the components, and results in a cement with open macroporosity enabling a rapid bone ingrowth.

Abstract: A microemulsion delivery system for water insoluble or sparingly water soluble drugs that comprises a long polymer chain surfactant component and a short fatty acid surfactant component, with the amount of each being selected to provide stable microemulsion or micellar systems.

Abstract: The invention concerns delivery particles (DP's) for active principles (AP's) based on linear amphiphilic polyamino-acids (PAA's), with &agr;-peptide chains, capable of being spontaneously formed by contacting PAA's with a liquid medium, preferably with water, wherein the hydrophile part of the PAA's is solubilized more than the hydrophobic parts of said PAA's, such that the latter precipitate while being organised in discrete supra-molecular arrangements, of average size ranging between 0.01 and 20 &mgr;m, capable of combining with at least an AP and releasing the latter in vivo, in prolonged and controlled manner.

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: A microemulsion delivery system for water insoluble or sparingly water soluble drugs that comprises a long polymer chain surfactant component and a short fatty acid surfactant component, with the amount of each being selected to provide stable microemulsion or micellar systems.

Abstract: A process for producing microparticles containing biologically active substance, in which process an aqueous solution of the said substance is prepared, this solution is mixed with an aqueous solution of PEG such that the substance is concentrated and/or solidified, the substance is optionally washed, the substance is mixed with an organic polymer solution, the composition obtained is mixed, after the admixture of said polymer solution, with an aqueous polymer solution, thereby forming an emulsion of droplets of first mentioned polymer as the internal phase, said droplets are solidified into microparticles, the microparticles are dried and a release-controlling shell is optionally applied to these.

Abstract: A powdered, dispersible composition having stable dispersibility over time is provided. The composition exhibits a characteristic glass transition temperature (Tg) and a recommended storage temperature (Ts), wherein the difference between Tg and Ts is at least about 10° C. (i.e. Tg−Ts is greater than 10° C.). The composition comprises a mixture of a pharmaceutically-acceptable glassy matrix and at least one pharmacologically active material within the glassy matrix. It may be further mixed with a powdered, pharmaceutically-acceptable carrier. It is particularly valuable in unit dosage form having a moisture barrier, in combination with appropriate labelling instructions.

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 encapsulated in a moisture sensitive micro-particle. The 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.

Abstract: Particles having a tap density of less than 0.4 g/cm3 include a hydrophobic amino acid or salt thereof and a therapeutic, prophylactic or diagnostic agent or any combination thereof. Preferred particles include a phospholipid, have a median geometric diameter between about 5 and about 30 microns and an aerodynamic diameter between about 1 and about 5 microns. The particles can be formed by spray-drying and are useful for delivery to the pulmonary system.

Abstract: The present invention encompasses solid dose delivery systems for administration of guest substances. Preferred delivery systems are suitable for delivery of bioactive materials to subcutaneous and intradermal, intramuscular, intravenous tissue, the delivery system being sized and shaped for penetrating the epidermis. The delivery systems comprises a vitreous vehicle loaded with the guest substance and capable of releasing the guest substance in situ at various controlled rates. The present invention further includes methods of making and using the solid dose delivery systems.

Abstract: The invention concerns an anhydrous solid composition comprising at least a hydrophobic wax, an oil and talcum, having preferably the form of beads with size ranging from 1 to 10000 microns. The beads can contain a cosmetic or pharmaceutical active principle, pigments or an agri-food constituent. The invention also concerns the method for preparing said beads.

Abstract: Small diameter particles of biologically active molecules are produced by atomizing solutions of the molecules through a nozzle into very cold liquified gases, which immediately freeze the atomized droplets. The resulting frozen particles having diameters of approximately 10 to 90 micrometers are lyophilized to produce porous particles, suspended in a non-solvent for the molecules, and exposed to ultrasonic energy or homogenization to produce particles having diameters of 0.1 to 10 micrometers with greater than 70 to 95% of the initial biological activity of the molecules in solution.

Abstract: The present invention relates to polymeric microspheres as injectable, drug-delivery vehicles 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. Microspheres of less than 45 &mgr;m, preferably less than about 20 &mgr;m, and preferably about 0.1 &mgr;m to about 10 &mgr;m in mean diameter according to the present invention are also selectively taken-up and into astrocytes when delivered directly into the nervous tissues.

Abstract: A tocotrienol-containing powder prepared by a process wherein an oil containing a tocotrienol is treated with a lecithin, a cellulose and an emulsifying agent in water to form an emulsion, a powder substance is mixed with the formed emulsion to form a suspension and then the formed suspension is spray-dried. The powder containing tocotrienol, which has excellent storage stability and free flowability, can be used in preparing a tablet which comprises the powder compressed into a tablet form.

Abstract: A process for the preparation of pellets containing ≧50 wt. % of a pharmaceutical active ingredient having a solubility in water of ≧0.5 g/ml, by aqueous granulation of the mixture containing the active ingredient, extrusion, rounding and drying of the moist granules, using a mixture consisting of A) at least 50 wt. % of at least one active ingredient having a solubility in water of ≧0.5 g/ml, and B) at most 50 wt. % of the combination of a) a microcrystalline cellulose having an average particle size of 15 to 20 &mgr;m and b) a low-substituted hydropropyl cellulose having an average particle size in the range of 10 to 25 &mgr;m, the weight ratio of a):b) being in the range of 4:6 to 6:4.

Abstract: The present invention provides compositions comprising an anti-angiogenic factor, and a polymeric carrier. Representative examples of anti-angiogenic factors include Anti-Invasive Factor, Retinoic acids and derivatives thereof, and paclitaxel. Also provided are methods for embolizing blood vessels, and eliminating biliary, urethral, esophageal, and tracheal/bronchial obstructions.

Abstract: An antiviral product is comprised of at least three dosages forms, each of which has a different release profile, with the Cmax for the antiviral product being reached in less than about twelve hours. In one embodiment, there is an immediate release dosage form, as well as two or more delayed release dosage forms, with each of the dosage forms having a different release profile, wherein each reaches a Cmax at different times.

Abstract: An O/W medical fat emulsion for oral administration, which is capable of increasing the bioavailability of a medicine or the blood level thereof. The emulsion is composed of fat emulsion particles containing an oil component, an emulsifier and a medicine as the indispensable constituents and dispersed in water, characterized in that the average diameter of the particles in the fat emulsion ranges from 5 to 50 nm. A freeze-dried preparation of the emulsion is also included in the invention.

Abstract: A polymer blend is prepared by dissolving chitosan and a second polymer in an acidic aqueous solution to form an aqueous polymer blend, dehydrating said aqueous polymer blend, and recovering said polymer blend. The second polymer may be selected from the group consisting of polyether glycols including polyethylene glycols; cellulose esters including cellulose acetate; poloxamers; polysaccharides including dextran and guar; polyvinylpyrrolidones; polyvinyl alcohols; and mixtures or copolymers thereof. These polymer blends swell in an acidic environment and deswell in a more neutral or basic environment. This technology is valuable for the dispensing of biologically active material or drugs into a surrounding environment, especially the environment as is found in the gastrointestinal tract.

Abstract: A biodegradable polymer composition comprising: (a) a poly(phosphoester) biodegradable polymer and (b) at least one antineoplastic agent in an amount effective to inhibit the growth of a solid tumor, which is suitable for intratumoral administration to treat a mammal having a solid tumor.

Abstract: Sustained release local anesthetic formulations are administered intra articularly and/or into body spaces/cavities. The formulation is preferably a plurality of injectable microparticles including a local anesthetic and an effective amount of a biocompatible, biodegradable, sustained release material prolonging the release of the local anesthetic and optionally and a pharmaceutically acceptable, i.e., non-toxic, augmenting agent effective to prolong the duration of the local anesthesia for a time period longer than that obtainable without the augmenting agent.

Abstract: This invention discloses an orally administered pharmaceutical composition for the treatment of elevated levels of cholesterol and related conditions comprising a statin and fenofibrate in the form of microparticles of solid fenofibrate that are stabilized by phospholipid as a surface active substance, wherein a therapeutically effective amount of the composition provides the statin and a quantity of fenofibrate to a fasted human patient that is greater than 80% of the quantity of fenofibrate provided by the same amount of the composition when administered to the same patient who has been fed a high fat meal.

Abstract: The present invention relates to microcapsules with an aqueous core containing at least one water-soluble cosmetic or dermatological active principle, and with a polymeric and/or waxy envelope, in which the said envelope consists of at least one polymer chosen from polycaprolactone, poly(3-hydroxybutyrate), poly(ethylene adipate), poly(butylene adipate), cellulose esters of at least one C1-C4 carboxylic acid, copolymers of styrene and of maleic anhydride, copolymers of styrene and of acrylic acid, styrene-ethylene/butylene-styrene block terpolymers, styrene-ethylene/propylene-styrene block terpolymers and terpolymers of ethylene, of vinyl acetate and of maleic anhydride, and/or of at least one wax chosen from beeswax, polyglycerolated beeswax, hydrogenated plant oils, paraffin with a melting point above 45° C., and silicone waxes.

Abstract: Granular materials are obtainable by pressing mixtures of at least one pulverulent, rheology-modifying, carboxyl-containing polymer as main component and at least one oil-soluble component.

Abstract: A formulation and methods for inducing sustained regional local anesthesia in a patient comprising a substrate comprising a local anesthetic and an effective amount of a biocompatible, biodegradable, controlled release material prolonging the release of the local anesthetic from the substrate to obtain a reversible local anesthesia when implanted or injected in a patient, and a pharmaceutically acceptable, i.e., non-toxic, non-glucocorticoid augmenting agent effective to prolong the duration of the local anesthesia for a time period longer than that obtainable from the substrate without the augmenting agent.

Abstract: The present invention relates to a cosmetic composition in the form of a powder containing a particulate phase and a fatty phase, characterized in that the fatty phase contains at least one fatty acid ester or at least one fatty alcohol ester, the carbonaceous chain of the fatty acid or alcohol being branched and saturated, and containing 24 to 28 carbon atoms. It also relates to the cosmetic applications of such a composition.

Abstract: A formulation and methods for inducing sustained regional local anesthesia in a patient comprising a substrate comprising a local anesthetic and an effective amount of a biocompatible, biodegradable, controlled release material prolonging the release of the local anesthetic from the substrate to obtain a reversible local anesthesia when implanted or injected in a patient, and a pharmaceutically acceptable, i.e., non-toxic, non-glucocorticoid augmenting agent effective to prolong the duration of the local anesthesia for a time period longer than that obtainable from the substrate without the augmenting agent.

Abstract: The invention relates to starch capsules which protect various substances, such as peptides, proteins, particularly pharmaceutical peptides and proteins, drugs or flavouring agents or spices or enzymes against the effect of the environment or the intestines. Filled starch granules are coated with a suitable biopolymer such as starch or amylose.

Abstract: Bioabsorbable biocompatible polymers which provide a good match between their properties and those of certain tissue structures are provided. The bioabsorbable biocompatible polymers can be prepared with tensile strengths, elongation to breaks, and/or tensile modulus (Young's modulus) values of the tissues of the cardiovascular, gastrointestinal, kidney and genitourinary, musculoskeletal, and nervous systems, as well as those of the oral, dental, periodontal, and skin tissues. Methods for processing the bioabsorbable biocompatible polymers into tissue engineering devices are also provided.

Abstract: The present invention are dry-feel emollient compositions comprising jojoba oil based esters that have use in personal care, cosmetic, cosmaceutical and pharmaceutical products. These compositions are essentially solid at room temperature, can be provided in various shapes and sizes (especially as particulates such as spheres), and can be produced from combinations of fatty alcohols, isopropyl esters and wax esters obtained from the oil contained in the seed of the jojoba plant. These new compositions also increase the range of applications for cosmetic compositions through an emollient that is more polar and hydrophilic than is found in jojoba oils. The compositions of the present invention may be obtained by a novel process of a base catalyzed alcoholysis reaction between jojoba oil and an alcohol, such as isopropyl alcohol.