US20070116728A1 - Novel galenical system for active transport, method for preparation and use - Google Patents

Novel galenical system for active transport, method for preparation and use Download PDF

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Publication number
US20070116728A1
US20070116728A1 US10/550,027 US55002704A US2007116728A1 US 20070116728 A1 US20070116728 A1 US 20070116728A1 US 55002704 A US55002704 A US 55002704A US 2007116728 A1 US2007116728 A1 US 2007116728A1
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Prior art keywords
wax
galenic system
particles
mix
active constituent
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Abandoned
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US10/550,027
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English (en)
Inventor
Karim Ioualalen
Rose-Anne Raynal
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ORALANCE PHARMA
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ORALANCE PHARMA
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Assigned to ORALANCE PHARMA reassignment ORALANCE PHARMA ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: IOUALALEN, KARIM, RAYNAL, ROSE-ANNE
Publication of US20070116728A1 publication Critical patent/US20070116728A1/en
Priority to US12/767,248 priority Critical patent/US8911788B2/en
Assigned to CAPSUGEL FRANCE reassignment CAPSUGEL FRANCE DEED OF SALE Assignors: ORALANCE PHARMA
Priority to US14/523,999 priority patent/US9192679B2/en
Abandoned legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/65—Tetracyclines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P23/00—Anaesthetics
    • A61P23/02—Local anaesthetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches

Definitions

  • This invention relates to a new galenic system for the protection of an active constituent, particularly a medicine, against degradation during transit in the stomach following oral absorption.
  • the galenic system according to the invention also enables masking of the taste of an active constituent in the galenic system, if any, stabilisation of the said active constituent, modulation of the release properties of the said active constituent, masking or mucosal irritability effects and toxicity of some active constituents.
  • Galenic forms intended to be taken orally are essentially in two forms, liquid and dry. They have the enormous advantage that they do not require any medical treatment when taking medicine.
  • the pH of the stomach is between 2 and 6.
  • the acid nature of the stomach environment can cause degradation of active constituents contained in ingested compositions before they have reached the intestine, where theoretically they are absorbed through the intestinal mucous membrane to pass into the circulation.
  • Such a deleterious stomach transit effect could be contradictory to the objective, namely absorption of the said active constituent by the organism in the most efficient form for the required effect.
  • This disadvantage is particularly important for pharmaceutical compositions.
  • galenic forms intended to be taken orally, particularly galenic forms for medical purposes.
  • a recurrent problem with these galenic forms is compliance.
  • Compliance is a capital factor that directly depends on the efficiency of the therapeutic treatment. Compliance, or correct use of the medicine, is defined as being the action of following a medical treatment in accordance with the indications in the prescription; respecting the treatment duration, the number of times and the times during the day that the medicine is taken. A medicine may be inactive or not very efficient if is not taken at a sufficient dose or sufficiently frequently. For intermittent disorders, failure of correct compliance of the treatment can only delay the cure and lead to relapses, sometimes responsible for serious complications. Poor compliance in the case of chronic diseases can cause irreversible damages.
  • Another of the objectives of this invention is to propose a galenic system capable of efficiently concealing the taste.
  • Another purpose of this invention is to propose a galenic system capable of a delayed release of an active constituent, particularly so that it is not released into stomach during ingestion.
  • This property requires the use of a galenic system stable in an acid medium, in other words resistant to an acid pH.
  • Coating techniques consist of putting a layer of isolating compounds, polymers and mixes into place around the active constituent to isolate it from the external environment.
  • Many natural and synthetic polymer compounds have been used to build up this external layer. They include mainly cellulose derivatives such as hydroxypropylmethylcellulose (HPCM), ethylcellulose, carboxymethylcelluloses, hydroxypropylmethylcellulose phthalate or mixes of these products.
  • HPCM hydroxypropylmethylcellulose
  • ethylcellulose carboxymethylcelluloses
  • hydroxypropylmethylcellulose phthalate mixes of these products.
  • Immediate release at the digestive tube depends on the use of a dependent pH polymer very sensitive to a pH greater than 7 in the mouth cavity or the stomach, which requires the addition of acid into the final formulation.
  • this invention proposes a new galenic system enabling:
  • the galenic system according to the invention is characterised in that it is composed of a mix of hydrophobic compounds insoluble in water, in that it is in solid form at ambient temperature and that it has absolutely no surfactant compounds, solvent residues or water that could cause hydrolysis or oxidation reactions of an active constituent containing it.
  • This galenic system has the capability of incorporating hydrophilic, hydrophobic or mineral type compounds.
  • the purpose of the invention is a strictly hydrophobic galenic system in the form of solid lipidic particles, containing no water or surfactants, or emulsifying agents or traces of solvents, characterised in that it comprises at least one hydrophobic wax and at least one non-neutralised fatty acid.
  • the galenic system is also talc free.
  • the lipidic particles are solid at a temperature of up to 45° C. and preferably up to 37.5° C.
  • the lipidic particles are in spherical form.
  • a hydrophobic wax according to the invention means that the galenic system may be composed of one or several vegetal, animal or mineral waxes, or a mix of one or several waxes and at least one non-amphiphilic oil.
  • the galenic system may also comprise at least one hydrophobic compound capable of adjusting the melting point and the physicochemical properties such as the hardness.
  • hydrophobic compounds include beeswax and palm oil.
  • compositions compatible in terms of toxicity, biocompatibility, non-immunogenicity and biodegradability with absorption by mouth or any other administration method, should be chosen.
  • the compounds will be chosen from among compounds already used for oral administration such as those defined in the GRAS list published by the Food and Drug Administration, such that the particles formed maintain their incorporation, taste concealing and stabilisation properties for active constituents.
  • the wax may be chosen from among any known wax compatible with the requirements of the invention.
  • the wax may be chosen from among:
  • the wax may be a mix of waxes.
  • a wax or a mix of waxes with a melting point of between 15° C. and 75° C., and preferably between 30° C. and 45° C. can be used.
  • the quantity of wax may be between 0.5% and 99%, and preferably between 1% and 50%.
  • the non-neutralised fatty acid may be any non-neutralised fatty acid compatible with the requirements of the invention.
  • the non-neutralised fatty acid may be chosen from among fatty acids with linear chains with between 4 and 18 carbon atoms, for example such as myristic acid, lauric acid, palmitic acid or oleic acid.
  • the non-neutralised fatty acid may be composed of a mix of non-neutralised fatty acids.
  • the non-neutralised fatty acid may be used with a fatty acid content by mass of between 0.5% and 75% and preferably between 1% and 30%.
  • the galenic system according to the invention may also contain oily, pasty or solid additives, liposoluble or hydrosoluble active ingredients.
  • compositions according to the invention may contain an oil or a mix from among:
  • oily compounds such as oleic alcohol, lanoline, sunflower oil, palm oil, olive oil, fatty acids and fatty alcohols may be used, but the oily mix obtained must be characterised by a hydrophobic behaviour, a lack of miscibility with water and a melting point between 15° C. and 75° C., and preferably between 30° C. and 45° C.
  • Clays or oily dispersions of clays, phenyl silicon gums, starches and fatty body structuring agents, can be added into the composition to adjust the consistency.
  • a number of compounds such as mineral fillers can be added to the hydrophobic matrix of the galenic system, to modulate the density and plasticity.
  • Talc and kaolin will advantageously be chosen for the mineral compounds.
  • the size of lipidic particles according to the invention may be between 0.5 microns and 1500 microns, and preferably between 10 microns and 250 microns.
  • Lipidic particles according to the invention have the advantage that they can enable delayed release of an active constituent contained in them, very good stability to an acid pH particularly in an acid aqueous formulation, thus enabling protection of the active constituent when they are in contact with an environment with an acid pH, for example such as the gastric environment, and complete concealing of the taste.
  • Another purpose of the invention is a galenic system according to the invention also comprising an active constituent.
  • the term active constituent is used to denote any substances that can be used in cosmetics, pharmacy, biotechnology, in the veterinary field or in food.
  • the active constituent may be an active therapeutic substance that can advantageously be administered to man or other animals to diagnose, cure, reduce, treat or prevent a disease.
  • the active constituent may be any hydrophilic, hydrophobic or mineral compound.
  • the active constituent may be dissolved or dispersed in the galenic system.
  • the active constituent may be a mix of active constituents.
  • the active constituent may be chosen from among essential oils, aromas, pigments, fillers, colouring agents, enzymes and coenzymes and other active substances.
  • Active constituents that may be incorporated into the galenic system according to the invention include vitamins or provitamins A, B, C, D, E, PP and their esters, carotenoids, anti-radical substances, hydroxyacids, antiseptics, and molecules acting on the pigmentation, inflammation, biological extracts.
  • the active constituent may also be chosen from among preservatives, antioxidants, colouring agents and pigments, cells and cellular organites or pharmaceutical compounds intended for the treatment of pathologies, particularly skin or mucosal pathologies.
  • therapeutic active constituents examples include antibiotics, antifungicides, antiparasites, anti-malaria agents, adsorbents, hormones and derivatives, nicotine, antihistamines, steroidal and non-steroidal anti-inflammatory agents, antiallergic agents, antalgics, local anaesthetics, antivirals, antibodies and molecules acting on the immunitary system, cytostatics and anticancer agents, antalgics, hypolipemiants, vasodilators, vasoconstrictors, inhibitors of the angiotensin and phosphodiesterase conversion enzyme, nitrated and antianginal derivatives, beta-blocking agents, calcium inhibitors, antidiuretics and diuretics, bronchodilators, opiates and derivatives, barbiturates, benzodiazepines, molecules acting on the central nervous system, nucleic acids, peptides, anthracenic compounds, paraffin oil, polyethylene glycol,
  • the lipidic particles also comprise an active constituent and have a melting temperature after the active constituent has been incorporated of between 15° C. and 75° C., and preferably between 300 and 45° C.
  • the capacity of particles for holding an active constituent may vary from 0.02% to 75% by weight of the particles, and particularly from 5 to 50%.
  • an appropriate lipidic composition should be chosen such that the particles are solid at the temperature of use with a size preferably between 0.5 microns and 1500 microns and preferably between 0.5 microns and 100 microns, to completely conceal the taste without modifying the release properties and with very good stability in an aqueous formulation even at a high pH. It is also necessary that the process for preparation of the said galenic system also comprising an active constituent can be used.
  • the galenic system also comprising an active constituent may be prepared using the process described in patent WO 99/65448.
  • the particles are obtained by mixing with moderate heating. More specifically, these compositions are obtained by a process characterised by the fact that wax and oil are mixed at the melting temperature of the wax to obtain a mix characterised by a melting temperature less than the melting temperature of the wax.
  • the initial ratio between the wax and the oil may be modulated so that the melting temperature of the final mix is less than the degradation temperature of the compound to be incorporated that is most sensitive to heat.
  • the final mix must be solid at the temperature of use and in one of these preferred forms it must have a melting point of 37.5° C.
  • the mix is then cooled with appropriate stirring, to a temperature of more than 2° C. or 3° C. at its melting point, to enable inclusion of pharmaceutical active constituents.
  • the mix is then formed to result in hydrophobic spherical particles called particles.
  • the process according to the invention does not involve any emulsifying agents or amphiphilic products in the composition, to enable stable dispersion during the solidification phase by cooling.
  • the invention when the active constituent has to be completely eliminated from the surface of lipidic particles, the invention includes a step to wash the said particles obtained with a washing mix including ethanol.
  • a washing mix including ethanol In this case, the presence of ethanol in the washing mix is essential to the process since ethanol enables complete washing of any active constituent residues that may be present on the surface of the lipidic particles that could create an unpleasant taste.
  • the different compounds in the galenic system including wax and non-neutralised fatty acid
  • the active constituent are mixed in a first step of the process.
  • the mix is made hot at 2° C. or 3° C. above the melting point of the compound with the highest melting point.
  • a stirring method appropriate to the dispersion of all compounds must be used.
  • lipidic droplets comprising the active constituent by dispersing the mix obtained in the first step in a gel prepared with a gelifying, shear thinning and non surface active agent with which the said mix is not miscible, previously adjusted to the same temperature, and with a concentration of gelifying agent between 0.1 g/l and 30 g/l, and preferably between 0.2 g/l and 20 g/l sufficiently high to fix the dispersion.
  • Stirring must be continued throughout injection and has a characteristic of using a blade equipped with an anchor designed to disperse the composition and a second axial blade equipped with a three-vaned impeller designed to for dispersion droplets with the required size.
  • This final step is extremely fast because the droplets are obtained as the composition is being injected. There is no need to maintain stirring after the end of injection, because the droplets are fixed in the gel.
  • the droplets are immediately cooled to below this mix solidification temperature at the end of the injection and are then washed.
  • the washing phase is very important because it makes it possible to no longer have any residue on the surface of particles, which could create an unpleasant taste.
  • particles may be washed using a washing mix composed of water and between 0% and 25% of ethanol.
  • the washed particles are then recovered by sieving and are then dried.
  • the particles obtained have excellent size homogeneity and can be manipulated industrially with no special precautions.
  • the process according to the invention is fast and does not require any long and difficult stirring step. It can incorporate the active constituent into the galenic system during the first mixing step of the different ingredients in the composition.
  • shear thinning and non-surface active gelifying agents appropriate for formation of the gel used as the dispersion medium according to the process, include carboxyvinyl polymers such as polyacrylic polymers not modified by hydrophobic groups or surfactants, carrageenans, thickeners and polysaccharidic gels such as xanthenes, guar and carob gums, alginates, cellulose derivatives, pectins, agar or a mix of these products.
  • Lipidic particles comprising an active constituent may be incorporated into any composition, and particularly into any cosmetic, pharmaceutical, veterinary or food composition.
  • compositions comprising at least one lipidic particle containing an active constituent.
  • composition according to the invention may also include any additive intended to modify the appearance or the rheology.
  • lubricants can be added to the dry powder of particles to improve their fluidity, for example such as talc, starches, silica powders, antistatic agents.
  • the composition according to the invention may be in the form of any appropriate galenic formulation.
  • the particles according to the invention are used in aqueous suspensions, syrups and sachets.
  • the particles may be used in conventional galenic formulations such as capsules, gelatine capsules, granules, oral powders, dispersible powders, tablets, hydrodispersible and orodispersible tablets.
  • the compositions may be used for administration by injection and particularly for the preparation of forms with prolonged release.
  • lipidic particles according to the invention are prepared so that their size is preferably between 0.5 ⁇ m and 5 ⁇ m. It is preferable to sieve them to obtain a size distribution conform with the mode of administration.
  • Their waxy composition is chosen to be conform with the requirements for injection. This galenic form can eliminate toxicity problems encountered by polymeric particles obtained using polymerisation in emulsion processes, related to the use of solvents and surfactant compounds.
  • the particles according to the invention can be used to obtain contents of the active constituent equal to between 0.10 and 2 grams/gram of waxy matrix. Those skilled in the art know that these contents cannot be reached using encapsulation technologies. Finally, particle degradation does not cause any inflammatory reaction like the reaction that can occur with injectable particles based on a polylactic-glycolic polymer.
  • the compound with the highest melting point in a thermostat controlled receptacle is heated to 2° C. above its melting temperature, and the different compounds are then added gradually, in order of their melting point, from the highest melting point to the lowest melting point.
  • the mix temperature is gradually reduced to be kept at 2° C. to 3° C. above the melting temperature of the new mix obtained.
  • the erythromycine is added last.
  • the mix When the mix is homogenous, it is added to 600 ml of aqueous gel with 0.2% of Ultrez 10 carbopol, neutralised to pH 6.5 with soda, previously adjusted to the same temperature as the lipidic mix and contained in a reaction vessel equipped with a stirring system with a three-vaned impeller.
  • the stirring speed of the three-vaned impeller is 110 rpm during addition of the composition. Stirring is maintained for 30 seconds after the composition has been added and is then stopped.
  • the dispersion is then cooled to 15° C.
  • the particles are recovered by and then washed with distilled water, then with a mix of distilled water with 15% of ethanol, and are then recovered and dried.
  • the average size of the particles thus obtained is 62 microns. These particles have no active constituent on their surface.
  • the erythromycin on the particles is analysed by HPLC. 29.3 g of erythromycin is obtained per 100 g of matrix.
  • compositions containing erythromycin have s strong taste.
  • the active constituent was not detected during the taste test carried out on the particles.
  • a pharmaceutical saccharose syrup distributed by the Cooper company and called Simple Syrup is used, with the following composition: Saccharose 86.50 g Sodium methyl parahydroxybenzoate 0.15 g Sodium propyl parahydroxybenzoate 0.03 g Pure water to make 100 ml
  • the powder After mixing, the powder is distributed in 2.24 g individual sachets containing 500 mg of erythromycin.
  • An aqueous dispersion of the antibiotic is reconstituted by dissolution in 50 ml water. The active constituent was not detected during the taste test carried out on the dispersion.
  • the operating method is exactly the same as that described in example 1.
  • the active constituent was not detected during the taste concealing test carried out on the particles.
  • the particles were obtained by dispersion of the lipidic phase in the gelified aqueous phase while stirring.
  • the concentration of carbopol in the aqueous phase is 0.05%.
  • Stirring is done using an axial turbo-stirring rod at a speed of 300 rpm, so as to reduce the average size of particles to 1 ⁇ m. Stirring is maintained for 60 seconds after the end of addition of the composition and is then stopped.
  • the dispersion is then cooled to 15° C.
  • the particles are recovered by sieving and are then washed with distilled water, and then by a mix of distilled water with 15% of ethanol, and are then recovered and dried.
  • the average size of the particles thus obtained is 1.2 microns.

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US10/550,027 2003-03-24 2004-03-24 Novel galenical system for active transport, method for preparation and use Abandoned US20070116728A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US12/767,248 US8911788B2 (en) 2003-03-24 2010-04-26 Galenical system for active transport, method for preparation and use
US14/523,999 US9192679B2 (en) 2003-03-24 2014-10-27 Galenical system for active transport, method for preparation and use

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR0303568A FR2852843B1 (fr) 2003-03-24 2003-03-24 Systeme galenique permettant le masquage du gout
FR03/03568 2003-03-24
PCT/FR2004/000729 WO2004084856A2 (fr) 2003-03-24 2004-03-24 Nouveau systeme galenique pour le transport d’actif, procede de preparation et utilisation

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
PCT/FR2004/000729 A-371-Of-International WO2004084856A2 (fr) 2003-03-24 2004-03-24 Nouveau systeme galenique pour le transport d’actif, procede de preparation et utilisation

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US12/767,248 Continuation US8911788B2 (en) 2003-03-24 2010-04-26 Galenical system for active transport, method for preparation and use

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US20210186889A1 (en) * 2018-03-23 2021-06-24 Eneapharm Intestinal-release formulation of a digestive enzyme, method of production and galenic preparation
CN113308045A (zh) * 2021-05-28 2021-08-27 宁波市鑫晟工贸实业有限公司 一种抗老化的塑料盒及其制备方法
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Publication number Priority date Publication date Assignee Title
US20100086595A1 (en) * 2007-03-21 2010-04-08 Oralance Pharma Faculte De Medecine Cochin Non-ionizable hydrophobic galenical system
US20090318554A1 (en) * 2008-06-23 2009-12-24 International Flora Technologies Ltd. Cosmetic particles that transform from hard to soft particles comprising hydrogenated long-chain triglyceride oils
US8613956B2 (en) * 2008-06-23 2013-12-24 International Flora Technologies, Ltd. Cosmetic particles that transform from hard to soft particles comprising hydrogenated long-chain triglyceride oils
WO2015189726A1 (en) 2014-06-10 2015-12-17 Capsugel Belgium Nv Orally disintegrating tablet containing solid lipid particles and methods for their preparation and use
EP3766480A1 (en) 2014-06-10 2021-01-20 Capsugel Belgium NV Orally disintegrating tablet containing solid lipid particles and methods for their preparation and use
RU2733739C1 (ru) * 2016-12-08 2020-10-06 Сальсарюло Фарма Пероральный лекарственный препарат, включающий осмотическое слабительное, заключенное в матрицу на основе растительных жиров
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AU2019229718B2 (en) * 2018-03-08 2025-02-13 Karim Ioualalen Gastroprotected, hydrophobic formulation of at least one active principle and method for obtaining same
US20210186889A1 (en) * 2018-03-23 2021-06-24 Eneapharm Intestinal-release formulation of a digestive enzyme, method of production and galenic preparation
CN113308045A (zh) * 2021-05-28 2021-08-27 宁波市鑫晟工贸实业有限公司 一种抗老化的塑料盒及其制备方法

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FR2852843B1 (fr) 2008-05-23
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US8911788B2 (en) 2014-12-16
JP5072355B2 (ja) 2012-11-14
WO2004084856A3 (fr) 2004-11-25
EP1605918A2 (fr) 2005-12-21
US9192679B2 (en) 2015-11-24
MXPA05010217A (es) 2006-03-28
CA2519962A1 (fr) 2004-10-07
US20150044297A1 (en) 2015-02-12
FR2852843A1 (fr) 2004-10-01
JP2006521334A (ja) 2006-09-21
EP1605918B1 (fr) 2016-09-28
WO2004084856A2 (fr) 2004-10-07
AU2004224601A1 (en) 2004-10-07
US20100221298A1 (en) 2010-09-02
CA2519962C (fr) 2015-03-10

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