WO1995005806A1 - Microparticules, leurs procedes de production et leur utilisation pour la preparation des medicaments - Google Patents

Microparticules, leurs procedes de production et leur utilisation pour la preparation des medicaments Download PDF

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Publication number
WO1995005806A1
WO1995005806A1 PCT/EP1994/002749 EP9402749W WO9505806A1 WO 1995005806 A1 WO1995005806 A1 WO 1995005806A1 EP 9402749 W EP9402749 W EP 9402749W WO 9505806 A1 WO9505806 A1 WO 9505806A1
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WO
WIPO (PCT)
Prior art keywords
microparticles
meth
process according
acrylate
poly
Prior art date
Application number
PCT/EP1994/002749
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English (en)
Inventor
Wolfgang Lahr
Original Assignee
Henning Berlin Anlagen Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Henning Berlin Anlagen Gmbh filed Critical Henning Berlin Anlagen Gmbh
Priority to AU76540/94A priority Critical patent/AU7654094A/en
Publication of WO1995005806A1 publication Critical patent/WO1995005806A1/fr

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Classifications

    • 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
    • A61K9/1682—Processes
    • A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
    • 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
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates

Definitions

  • Microparticles processes for their preparation and their use for the preparation of medicaments
  • the invention relates to novel microparticles and processes for their preparation and their use.
  • Classical microparticles as prepared and used, for example, in pharmacy as well as in other industrial sectors consist, as a rule, of a core, which constitutes a useful substance, in pharmacy generally a medicinal active substance, and a shell.
  • the core may consist of a solid, a liquid or a gas.
  • the shell material consists, as a rule, of an organic polymer which undergoes virtually no interaction with the core material and usually forms a closed surface (shell) .
  • microparticles are referred to as microcapsules or microspheres, the terms being used freely and without precise definition.
  • microcapsules in the narrowest sense of this term, are obtained by coacervation, i.e. by separation of highly solvatized colloids in the liquid phase; their shape is almost uniformly spherical or lemon-shaped.
  • Microspheres are, as a rule, designated as coated particles of an irregular type, and they are frequently crystals which are obtained by coating the particles with a film former, processes for their preparation being subject to technical limitations by virtue of the fact that single crystals must have a certain minimum size in order to obtain discrete particles.
  • pellets may be mentioned as further known particles, said pellets being shaped agglomerates which contain active substance, have diameters of up to several millimeters and, according to the prior art, can likewise be provided with shells, this being achieved by spraying on the dissolved wall material.
  • polymeric coating materials which are based on ( eth)acrylic acid derivatives have proved suitable for coating crystals and moldings, it being possible for said coating materials to be adjusted to give certain properties, in particular to give pH-dependent solubility properties, swelling properties and diffusion layers, by varying their chemical composition and the functional groups present in them.
  • Such (meth)acrylic acid derivatives are in particular the poly(meth)acrylate products known under the trade name Eudragit ® .
  • These poly(meth)acrylates are, as a rule, copolymers and are used in their original form for the film-coating of tablets by spraying them from organic solvent mixtures as coating material onto solid carriers.
  • Such poly(meth)acrylate resins containing organic solvents were used in the prior art also for microencapsulation (Benita et al., J. Pharm. Pharmacol. 1985, 37, 319-395; Fouli et al., Inf. J. of Pharmaceutics, 1983, 14, 95-102; Benita et al., J. Microencapsulation, 1985, Vol. 2, No.
  • poly(meth)acrylate polymers which are in the form of aqueous dispersions were developed.
  • Products having the trade name Eudragit ® can be recognized as' aqueous dispersions in that they are designated at the end of the product name with a "D" .
  • Such aqueous dispersions may replace the products based on organic solvents for many applications, and they are suitable in particular for coating relatively large particles, the particles obtained releasing the active substance contained in the core either in an acidic or in an alkaline medium in a pH-dependent or pH-independent manner, according to the particular property of the copolymers used.
  • Typical products of the Eudragit ® series have the trade designation L 30 D, E 30 D, RL 30 D and RS 30 D, E, L, RL and RS referring to certain properties/applications, the number 30 representing the concentration of polymer in the aqueous dispersion and D standing for dispersion.
  • aqueous poly(meth)acrylate dispersions have the disadvantage of tack during the spraying period up to complete film formation, so that smaller particles, such as, for example, crystals having an average size of ⁇ 500 ⁇ , are virtually impossible to coat. It has therefore been necessary to date to process such active substances with the use of excipients to give coarse-particled granules or so- called pellets or tablets, which can then be coated by conventional spraying. For the intended uses of such aqueous dispersions to date, it is furthermore a known disadvantage that these dispersions tend to coagulate, and the coagulated dispersions cannot be redispersed and have therefore become unsuitable for their intended use.
  • microparticles and processes for their preparation which microparticles contain finely divided useful substances, in particular pharmaceutical active substances (medicament active substances) , preferably those having average particle sizes of ⁇ 500 ⁇ m, and can be prepared without the use of organic solvents in the form of discrete individual particles and permit the use for the preparation of various medicament forms in an advantageous manner.
  • pharmaceutical active substances medium active substances
  • microparticles according to Claim 1 a process according to Claim 8 and the uses according to Claims 20 to 22.
  • Advantageous embodiments of the microparticles and of the process for their preparation are described in the relevant dependent subclaims and furthermore are evident to a person skilled in the art from the following detailed description of preferred embodiments.
  • the present invention is based on the knowledge that it is possible to utilize the tendency of aqueous poly(meth) crylate dispersions to coagulate, which is usually regarded as disadvantageous, to incorporate water-insoluble or slightly water-soluble useful substances, in particular medicinal active ingredients, into the poly(meth)acrylate particles of the aqueous dispersions, which particles are enlarged by controlled coagulation.
  • a particular advantage of the present invention is that, preferably, fine active substance particles, in particular microcrystals, or very finely divided, noncrystalline (amorphous) active substances can advantageously be enclosed by the coagulating poly(meth)acrylate by the process according to the invention, so that, depending on the process conditions, discrete particles are formed, the sizes of which are variable and can be adjusted by the coagulation conditions used.
  • Particle sizes obtainable are, as a rule, between 0.1 and 0.4 mm.
  • the active substance since, in the process according to the invention, the active substance must show a tendency to pass from an aqueous suspension into the coagulum particles, for the purposes of the present invention it is necessary, however, for the useful substances (medicinal active substances) to be insoluble or slightly .soluble in water or at least to be insoluble or slightly soluble in water under certain pH conditions. A large number of interesting and important medicinal active substances of pharmaceutical-therapeutic importance meet this requirement.
  • Antihypertensive agents such as dihydropyridines, hormones, such as oestrogens or progestogens, sulphonamides, such as sulfasalazine, and in particular those which are effective locally in the gastrointestinal tract, such as 5-aminosalicylic acid, psychopharmacological agents,. thyroid therapeutic agents, diagnostic agents, analgesics, alkaloids, corticoids, antigout agents and others, may be mentioned in this context. All these medicinal active substances can be incorporated according to the present invention in microparticles.
  • the present invention is not restricted to medicinal active substances, but other finely divided useful substances, for example dyes, pigments, vegetable substances, solid flavours or spices, dry extracts, agricultural chemicals, such as fertilizers or pesticides, plant parts or organic or inorganic dusts, can also be incorporated in the microparticles according to the invention under the same conditions, the person skilled in the art relying on the present invention when the microparticles according to the invention have particular advantages for the intended use, and of course economic considerations also being relevant in specific cases.
  • the definition of the terms "insoluble or slightly soluble in water” reference may be made to the relevant pharmaceutical technical literature, for example Martindale, The Extra Pharmacopoeia, 28th Edition, 1982, or other relevant pharmacopoeias. The corresponding definitions also apply to nonpharmaceutical active substances.
  • suitable aqueous poly(meth)acrylate dispersions are those which have been used and described to date primarily as film formers and, as a rule, are among the Eudragit products mentioned at the outset.
  • suitable aqueous poly(meth)acrylate dispersions which are described in the US Pharmacopoeia/National Formulary as "methacrylic acid copolymer, type C” (for example Eudragit LD, Rohm Pharma, Darmstadt, Germany) or as "ammonium methacrylate copolymer, type A or B" (for example
  • Eudragit NED Eudragit NED
  • aqueous poly(meth)acrylate dispersions constitute neutral, anionic or cationic copolymers of lower alkyl esters, in particular Cj . to C 4 -alkyl esters and in particular methyl, ethyl and butyl esters, of acrylic acid and of methacrylic acid, which, depending on the type, have certain contents of free carboxyl groups or tertiary amino groups or quaternary ammonium groups.
  • These poly(meth)acrylate dispersions are coagulated in a controlled manner in the presence of aqueous suspensions of useful substances to be incorporated, by preferably using strong electrolytes, such as inorganic salts with monovalent, divalent or trivalent cations and/or anions as coagulants.
  • These salts are preferably used in aqueous solution and either are added dropwise to the aqueous dispersion or are initially taken and the aqueous dispersions added dropwise.
  • Salts which are suitable as coagulants are, for example, sodium chloride, calcium chloride, magnesium chloride, sodium carbonate, sodium sulphate, sodium phosphate, potassium chloride and corresponding ammonium salts and mixtures of such salts.
  • the stated salts can advantageously be used owing to their sufficiently good water solubility, their concentrations as such not being critical. However, it is useful to work as far as possible with high concentrations in order to keep the liquid volume as small as possible during the preparation process.
  • the microparticles can be prepared in a convenient manner at room temperature or in an adjacent temperature range, temperatures of +4°C to +60°C having proved suitable.
  • suitable adjustment of the coagulation temperature heat sensitivities or solubility properties of the substances to be incorporated in the microparticles can be appropriately taken into account.
  • microcrystalline cellulose 10 microcrystalline cellulose, colloidal silica, stearic acid or salts thereof, talc or mixtures of the stated substances may be mentioned as examples.
  • the particles treated with lubricants can be isolated from the aqueous phase in a convenient manner by known methods,
  • the particles obtained can optionally be washed and dried or can be subjected to any suitable further processing in the moist state.
  • the filter residue obtained on filtration is dried, it either gives a powder of the microparticles directly or, when it forms a coherent filter cake, can subsequently be readily separated into individual particles using suitable sieves, without the
  • microparticles being destroyed. Since these do not have a sensitive shell as in the case of known microparticles, but are compact particles containing the active substance, they are extremely stable.
  • microparticles according to the invention is very simple, in contrast to known coating methods.
  • the active substance to be processed In order to be incorporated during the coagulation of the poly(meth)acrylate dispersions, the active substance to be processed must be present in suspension in the
  • aqueous phase of the dispersion 35 aqueous phase of the dispersion.
  • suspending the useful substance or the active substance it may be useful in the case of very fine, agglomerated substances to ensure particle separation by using, for example, ultrasonics or high-speed mixers. In the case of highly hydrophobic substances, the wettability and hence the suspendability can be improved by adding very small amounts of wetting agents.
  • stirring is therefore carried out, the stirring speed at least ensuring homogeneity of the suspensions, and the active substance suspension is mixed with the aqueous polymer dispersion while stirring, it being possible to add the dispersion to the suspension, or vice versa.
  • the precipitating agent is added dropwise to the resulting aqueous mixture of the suspension of the useful substance and the dispersed poly(meth)acrylate particles, as a rule in the form of an aqueous solution of a selected salt suitable as a coagulant, until the total useful substance has been enclosed in the coagulum being formed.
  • the process is complete when a two-phase system consisting of microparticles and a clear aqueous phase has formed.
  • the reverse procedure may also be adopted, namely the coagulant can be initially taken in the form of an aqueous salt solution and the aqueous mixture of the suspension and dispersion can be added dropwise.
  • the process is carried out batchwise and discontinuously.
  • a flow reactor for example a mixing tube, and to recover the particles continuously from the product stream after the gradual combination of all components.
  • the ratio of aqueous poly(meth)acrylate dispersion to suspended active substance for the formation of the microparticles is of course dependent on the desired concentration ratios in the prepared microparticles and is also influenced by the constitution of the active substance to be processed.
  • the weight ratios of useful substance/active substance to poly(meth)acrylate polymer can be varied within wide limits, it being possible, for example, for the contents of the useful substance in the microparticles to be in the range from 5 to 65% by weight, in particular in the range from 5 to about 30% by weight, the total weight of the dry microparticles serving as a reference basis.
  • microparticles according to the invention can be prepared in sizes from'about 10 to 800 ⁇ m, preferably from 100 to 400 ⁇ m, the shape and particle size being influenced essentially by the particle size of the active substance used, but additionally also being capable of being influenced in a specific manner by the stirring speed, stirrer shape, stirring time and type, amount and rate of addition of the coagulant.
  • Eudragit* L 30 D is used as the poly(meth)acrylate, it is necessary, for example, to " take into account the fact that this product is soluble in a weakly acidic to alkaline medium, which would prevent controlled coagulation in a corresponding medium.
  • the controlled coagulation can readily be carried out in an acidic medium at, for example, pH 1.5.
  • plasticizers such as, for example, polyethylene glycol, citric esters, plasticizing phthalates or propylene glycol, may be added to the starting dispersion, said plasticizers, like any acids added, remaining in the aqueous phase or passing over into said phase, with the exception of traces, and thus no longer being present in the microparticles isolated.
  • plasticizers like any acids added, remaining in the aqueous phase or passing over into said phase, with the exception of traces, and thus no longer being present in the microparticles isolated.
  • a so-called tablet disintegrant which allows the tablets to disintegrate rapidly in contact with an aqueous liquid can preferably be added to the dry mixture.
  • the discrete microparticles are released without the shell materials sticking together. It has furthermore been found that, after disintegration of the tablets, the microparticles are virtually unchanged, in contrast to microcapsules or pellets which are damaged or destroyed to a considerable extent on compression and hence lose their function.
  • Medicament-containingtablets comprisingmicroparticles according to the invention thus also have the advantage that a patient can also allow the tablets to disintegrate in liquids, for example fruit juices, and thus ' has no difficulties with consumption. This advantage can also be utilized by offering bulky tablets which are usually rejected by the patient.
  • the microparticles according to the invention it is possible to offer a patient medicaments for oral or peroral administration which are more convenient to take and at the same time improve the compliance.
  • the microparticles can also be filled directly into hard gelatine capsules or, in the form of powder, into sealed bags, without further technical processing being required. Furthermore, the microparticles can also be suspended in suitable aqueous gel formulations, so that ready-to-swallow liquid medicament formulations can be prepared.
  • the microparticles according to the invention completely reproduce the properties, known per se, of the aqueous poly(meth)acrylate dispersions used as starting materials.
  • the microparticles according to the invention can therefore be prepared as a form which is soluble in gastric fluid, a form which is soluble in the intestine or a sustained-release form.
  • medicament- containing microparticles according to the invention have the advantage over other, medicament forms that they rapidly pass through the stomach after oral intake and are therefore suitable for reducing the active substance-induced side effects of many active substances, which are due to release in the stomach.
  • the active substances can be brought in a controlled manner to the desired site of action or absorption site, and, if desired, a. time-dependent release of the incorporated active substance of the microparticles is also achieved (sustained release) .
  • Eudragit* L 30 D 1.5 g of Eudragit* L 30 D, corresponding to 0.45 g of dry substance, are dispersed in 60 g of water.
  • Example 2 (average molecular weight 6000) in 45 g of water are added dropwise as coagulation medium under the same stirring conditions. Discrete microparticles which quantitatively enclose the finely divided active substance are formed. 0.5 g of micronized talc and 30.0 g of microcrystalline cellulose are added as lubricants to the suspension. Thereafter, the suspension obtained is heated to about 60°C for 5 minutes and then cooled, filtered, washed with water and dried.
  • Example 2
  • nifedipine 1.0 g of nifedipine is made into a paste and wet with the addition of a spatula tip of sodium laurylsulphate as a wetting agent in 10 ml of water. Thereafter, 90 g of water and 3.3 g of Eudragit' L 30 D, corresponding to about 1.0 g of dry substance, are added and vigorous stirring is carried out. 20 ml of a solution of 45 g of water, 5 g of sodium chloride and 0.6 g of polyethylene glycol 6000 are slowly added dropwise to the suspension, as a coagulation medium. Microparticles which enclose the active substance form spontaneously.
  • sulfasalazine 3.5 g are suspended in 1.26 kg of demineralised water. 31.5 g of Eudragit* 30 D and 70 g of a 10% polyethylene glycol 6000 solution are added while stirring with a paddle stirrer at 370 rpm. 140 ml of a 10% sodium chloride solution are added dropwise as the coagulation medium. After the further addition of a few drops of 6.5 molar hydrochloric acid, stirring is continued for a further 15 minutes. After the addition of 10 g of microtalc and 24.5 g of microcrystalline cellulose as lubricants, the suspension is heated to 30-35°C and is cooled to about 20°C and then filtered. The filter residue is washed with acidified water and dried. It is observed that the coagulation begins after the addition of 50 ml of the sodium chloride solution and is virtually complete after 100 ml. After drying, the product is separated into microparticles by means of a 1000 ⁇ m sieve.
  • 0.5 g of 5-aminosalicylic acid is separated into discrete crystals in 180 g of demineralised water with the action of ultrasonics for three minutes.
  • 4.5 g of Eudragit* L 30 D and 10 g of a 10% polyethylene glycol 6000 solution are added in succession while stirring at 60 rpm with a propeller stirrer.
  • 20 ml of 10% sodium chloride solution and then two drops of an approximately 6.5 molar hydrochloric acid are added as a coagulation medium with further stirring.
  • the microparticles formed are stirred for 15 minutes.
  • the suspension is heated to about 40°C, then allowed to cool and filtered, and the filter residue is washed with acidified water and dried.
  • Laevothyroxine-containing microparticles were prepared analogously to Example 4, except that, instead of the ultrasonic treatment for better wetting, a spatula tip of sodium laurylsulphate was added.
  • Example 5 0.5 g of oestradiol valerate was incorporated in microparticles analogously to Example 5.
  • Microparticles containing active carbon as the useful substance are prepared analogously to Example 4 from 0.25 g of suspended active carbon and 4.5 g of Eudragit* L 30 D, the process being modified so that the hydrochloric acid is added before the beginning of the precipitation process.
  • Example 9 The sulfasalazine-containing microparticles from Example 3 are mixed with 5% by weight of crosslinked polyvinylpyrrolidone (Collidon* CD as a disintegrant. The mixture obtained is pressed to give tablets having a diameter of 11 mm and a weight of 400 mg. The tablets have a compressive strength of 40 N, and the mechanical abrasion after 4 minutes in the Roche friabilator is zero.
  • 0.5 g of sulfasalazine are incorporated in microparticles according to the invention by means of controlled coagulation as in the preceding Examples.
  • hydrochloric acid an amount of 1.2 g of citric acid is dissolved in the suspension, and the addition of the lubricants is dispensed with.
  • 0.5 g of xanthan gum USP quality
  • the suspension is heated to 35°C and then cooled to room temperature.
  • Preservatives and flavours can, if required, be added to the particle suspension obtained, which is a consumable, oral dosage form which can be filled into conventional primary packaging materials.

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Preparation (AREA)

Abstract

On peut préparer des microparticules sous forme de particules d'un coagulum d'une dispersion aqueuse de poly(méth)acrylate contenant une ou plusieurs substances utiles légèrement solubles ou insolubles dans l'eau, de la manière suivante: on prépare une suspension d'une ou de plusieurs substances utiles légèrement solubles ou insolubles dans un milieu aqueux, en particulier des substances actives pharmaceutiques, dans la phase aqueuse d'une dispersion aqueuse de poly(méth)acrylate, et on fait coaguler de manière contrôlée les particules de poly(meth)acrylate de la dispersion, de préférence en ajoutant une solution d'un électrolyte fort.
PCT/EP1994/002749 1993-08-20 1994-08-18 Microparticules, leurs procedes de production et leur utilisation pour la preparation des medicaments WO1995005806A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU76540/94A AU7654094A (en) 1993-08-20 1994-08-18 Microparticles, processes for their preparation and their use for the preparation of medicaments

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DEP4328069.2 1993-08-20
DE4328069A DE4328069A1 (de) 1993-08-20 1993-08-20 Mikropartikel, Verfahren zu ihrer Herstellung und ihre Verwendung zur Herstellung von Arzneimitteln

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WO1995005806A1 true WO1995005806A1 (fr) 1995-03-02

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ID=6495658

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Application Number Title Priority Date Filing Date
PCT/EP1994/002749 WO1995005806A1 (fr) 1993-08-20 1994-08-18 Microparticules, leurs procedes de production et leur utilisation pour la preparation des medicaments

Country Status (6)

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AU (1) AU7654094A (fr)
DE (1) DE4328069A1 (fr)
IL (1) IL110685A0 (fr)
MX (1) MXPA94006337A (fr)
WO (1) WO1995005806A1 (fr)
ZA (1) ZA945892B (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019136053A1 (fr) * 2018-01-03 2019-07-11 Ferring B.V. Compositions pharmaceutiques liquides orales d'aminosalicylates
RU2804487C2 (ru) * 2018-01-03 2023-10-02 Ферринг Б.В. Жидкие фармацевтические композиции для перорального введения на основе аминосалицилатов

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DE19537415A1 (de) * 1995-10-09 1997-04-10 New Standard Gmbh Micro Wirkstoff-Perlen
DE10058771A1 (de) * 2000-11-27 2002-06-06 Falk Pharma Gmbh Coazervierungsverfahren zur Herstellung von verzögert feisetzenden Arzneimitteln
ATE374044T1 (de) * 2004-04-05 2007-10-15 Basf Ag Wirkstoffhaltige polymerteilchen
US7718164B2 (en) 2005-06-22 2010-05-18 L'oreal S.A. Optically colored body and optical structure
JP2007002074A (ja) * 2005-06-22 2007-01-11 L'oreal Sa 光学発色体及び光学構造体

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EP0207041A2 (fr) * 1985-06-12 1986-12-30 "Galephar" Comprimés pharmaceutiques permettant l'administration aisée de pellets, leur préparation et leur utilisation

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US4777089A (en) * 1985-05-08 1988-10-11 Lion Corporation Microcapsule containing hydrous composition
JPH04230625A (ja) * 1990-12-27 1992-08-19 Standard Chem & Pharmaceut Corp Ltd 噴霧乾燥したジクロフェナクナトリウムを含み腸溶性の被覆を有するマイクロカプセルからなる微分散した錠剤組成物の製造方法

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EP0036345A1 (fr) * 1980-02-26 1981-09-23 Roussel-Uclaf Nouveau procédé d'enrobage d'au moins un principe actif médicamenteux, les nouveaux médicaments ainsi obtenus, et les compositions les renfermant
EP0207041A2 (fr) * 1985-06-12 1986-12-30 "Galephar" Comprimés pharmaceutiques permettant l'administration aisée de pellets, leur préparation et leur utilisation

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019136053A1 (fr) * 2018-01-03 2019-07-11 Ferring B.V. Compositions pharmaceutiques liquides orales d'aminosalicylates
JP2021509664A (ja) * 2018-01-03 2021-04-01 フェリング ベスローテン フェンノートシャップ アミノサリチレートの経口液体医薬組成物
RU2804487C2 (ru) * 2018-01-03 2023-10-02 Ферринг Б.В. Жидкие фармацевтические композиции для перорального введения на основе аминосалицилатов

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MXPA94006337A (es) 2002-06-12
DE4328069A1 (de) 1995-02-23
AU7654094A (en) 1995-03-21
ZA945892B (en) 1995-03-10
IL110685A0 (en) 1994-11-11

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