WO1997012604A1 - Procede de production de preparations solides contenant des vitamines - Google Patents

Procede de production de preparations solides contenant des vitamines Download PDF

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Publication number
WO1997012604A1
WO1997012604A1 PCT/EP1996/004272 EP9604272W WO9712604A1 WO 1997012604 A1 WO1997012604 A1 WO 1997012604A1 EP 9604272 W EP9604272 W EP 9604272W WO 9712604 A1 WO9712604 A1 WO 9712604A1
Authority
WO
WIPO (PCT)
Prior art keywords
vitamin
vitamins
melt
preparations
weight
Prior art date
Application number
PCT/EP1996/004272
Other languages
German (de)
English (en)
Inventor
Joerg Rosenberg
Jörg Breitenbach
Original Assignee
Basf Aktiengesellschaft
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 Basf Aktiengesellschaft filed Critical Basf Aktiengesellschaft
Priority to AU72833/96A priority Critical patent/AU7283396A/en
Publication of WO1997012604A1 publication Critical patent/WO1997012604A1/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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Definitions

  • the present invention relates to a process for the production of vitamin-containing solid preparations by extrusion of a polymer melt containing us and subsequent shaping, as well as pharmaceutical forms from these preparations.
  • the preparation of active substance-containing preparations by melt extrusion is generally known.
  • the object of the present invention was to find an improved process for the production of vitamin preparations.
  • the vitamin-containing melt is preferably produced in the extruder at temperatures of 80 to 110 ° C.
  • a water-soluble, thermoplastically processable hydroxypropyl cellulose is preferably used as the polymer matrix for the vitamin-containing preparations, which preferably has a molar degree of substitution of 3.0 to 4.4.
  • “Moler degree of substitution” refers to the average Number of moles of propylene oxide that are converted per cellulose glucose unit.
  • the hydroxypropyl celluloses can have melt viscosities according to DIN 53735 in the range from 0.075 to 54.8 g / 10 min.
  • the molecular weight of the hydroxypropyl cellulose can be varied within a wide range, depending on whether a slower or a faster drug release is desired.
  • High molecular weight hydroxypropyl cellulose with molecular weights in the range from 200,000 to 1,500,000 are particularly suitable for the production of pharmaceutical forms in which a slow release of active substance is desired, e.g. in slow release forms, since the higher molecular polymers dissolve less well and only swell in water.
  • 60,000 to 200,000 preferably 60,000 to 100,000, can be used.
  • hydroxypropyl cellulose used according to the invention is generally known. They are commercially available, for example under the brand name Klucel® (from Aqualon).
  • the proportion of hydroxypropyl cellulose in the total amount of the dosage form can be 5 to 95% by weight, preferably 15 to 40% by weight.
  • Vitamins in the sense of the invention are also provitamins or vitamin derivatives.
  • Suitable vitamins are accordingly:
  • Thiamine (Bi), riboflavin (B 2 ), the B 6 vitamins pyridoxal, pyridoxamine and pyridoxine, cobalamins (B ⁇ ) such as cyanocobalamin, bio-tin, folic acid, nicotinic acid, nicotinamide, pantothenic acid,
  • Ascorbic acid and its physioligially tolerated salts such as ascorbyl palmitate
  • Vitamin F essential fatty acids
  • Vitamin F essential fatty acids
  • linolenic acid linoleic acid or arachidonic acid
  • Combination preparations can also be produced.
  • the dosage forms can the vitamins in amounts from 0.1 to
  • Type of vitamins the other depends on the use.
  • the pharmaceutical forms according to the invention can also contain customary pharmaceutical auxiliaries, provided that they are thermally stable under the processing conditions and are compatible with the vitamins used, e.g. Fillers, lubricants, plasticizers, stabilizers, dyes or pigments, disintegrants, preservatives of the flavorings.
  • Suitable fillers are, for example, organic compounds such as lactose, sorbitol or mannitol or inorganic substances such as silica or silicates.
  • Well water-soluble fillers such as xylitol, isomalt, lactose, sorbitol or mannitol are suitable, for example, for the preparation of preparations with accelerated release of active ingredients.
  • the proportion of fillers in the preparation depends on the dosage of the active ingredient. In the case of active ingredients with a low dosage, a higher tablet weight can be achieved according to the invention by means of higher filler proportions without the thermoplastic processability being impaired. At very low to dose materials, the amount of filler can be up to approximately 90% by weight.
  • Flow regulators such as the mono-, di- and triglycerides of the long-chain fatty acids such as C 2 , C 1, C 6 and C 6 fatty acid or waxes such as carnauba wax can be used in the usual amounts as further pharmaceutical auxiliaries.
  • plasticizers e.g. in addition to low molecular weight polyalkylene oxides such as polyethylene glycol, polypropylene glycol and polyethylene propylene glycol, also polyhydric alcohols such as propylene glycol, glycerin, pentaerythritol and sorbitol as well as sodium diethylsulfosuccinate, mono-, di- and triacetate of glycerol and polyethylene glycol stearic acid ester, these substances are not called, these substances are not called esters Show incompatibility with the vitamins used.
  • the amount of plasticizer is about 0.5 to 15, preferably 0.5 to 5 wt .-%.
  • lubricants e.g. Glycerol monostearate and other glycerol mono- and diesters and stearates of aluminum, magnesium or calcium as well as talc and silicones are mentioned, their amount being about 0.1 to 5, preferably 0.1 to 3% by weight.
  • compositions containing vitamins are particularly preferred which contain lipids as mold release agents and auxiliaries for influencing the plasticity of the melt.
  • the lipids present invention mono-, di- and triglycerides come from naturally occurring fatty acids into consideration beispiels ⁇ as glycerol, glyceryl, glycerol tristearate, Glyceroltripalmitat, GTM, glycerol tribehenate, Glycerolpalmitylstearylester or glyceride as occur in natural oils, preferably hydrogenated castor oil.
  • Ceramides are also suitable for this purpose.
  • Preferred lipids are primarily phospholipids, with phosphoglycerides such as lecithins being particularly preferred. Hydrogenated lecithins such as soya and egg lecitin are particularly preferred.
  • the lipids can be used in amounts of 0.1-10% by weight, based on the total amount of the active substance-containing preparations, 1 to 5% by weight being preferred.
  • Stabilizers which may be mentioned are, for example, light stabilizers, antioxidants, radical scavengers and stabilizers against microbial attack which can be used in the customary amounts.
  • flavoring and sweetening for example for use as a lozenge, natural, nature-identical or artificial flavors and sweeteners such as e.g. Cyclamate, aspartame, neoresperidin or saccharin sodium or mixtures thereof are used.
  • natural, nature-identical or artificial flavors and sweeteners such as e.g. Cyclamate, aspartame, neoresperidin or saccharin sodium or mixtures thereof are used.
  • the vitamins can either be melted directly as a physical mixture with the matrix polymer or can be mixed with the polymer melt already present.
  • the latter procedure is particularly recommended for very temperature-sensitive vitamins.
  • auxiliaries can be incorporated into the polymer melt together with the active ingredient. Mixtures of auxiliaries, the active ingredient and the polymers can also be melted directly.
  • the matrix polymer is melted and mixed with active ingredients and auxiliaries at from 50 to 150 ° C., preferably from 80 to 110 ° C., in a twin-screw extruder.
  • the vitamin-containing melt leaving the extruder can, as described in US Pat. No. 4,880,585, be pressed directly into tablets via opposing pairs of forming rolls.
  • processes for the production of small particles are also possible, e.g. by using the hot cutting process (extrusion of the melt through thin holes; cutting the extrudate strands directly in front of the die plate by rotating knives into pellets).
  • pellets are suitable e.g. for filling in hard gelatin capsules, but also as a preliminary stage for a subsequent tableting pressing process.
  • the process according to the invention is particularly suitable for the production of vitamin preparations which contain vitamins, provitamins or vitamin derivatives which are sensitive to oxidation and temperature.
  • Ascorbic acid can thus be processed largely without decomposition, which was surprising in view of the known temperature sensitivity of this substance.
  • ⁇ -carotene can also be processed excellently without significant isomerization taking place.
  • the storage stabilities of the formulations according to the invention were also good; after three months of storage at 10.degree. C., no losses of vitamins were found, for example.
  • the vitamin preparations produced according to the invention can be used for pharmaceutical or veterinary purposes
  • compositions containing carotenoids can also be used for coloring foods.
  • the area of application is animal nutrition.
  • the raw materials listed in the table were mixed to-35 present in an adequate mixer and entered h as a mixture in the ex ⁇ screw extruder via a weigh feeder with capacities ranging from 20 to 30 kg /.
  • the speed of the extruder screw was in al ⁇ len cases from 100 to 150 rev / min.
  • the vitamin C content of a sample according to Example 3 was analyzed a few days after production using an HPLC method (isocratic system). The actual value found was 41.46% by weight (target value: 41.66% by weight), and no by-products were observed. The actual values found for the beta-carotene were 3.8% by weight (target: 3.34% by weight), of which 90.7% were all-trans-beta-carotene.
  • the vitamin-containing tablets according to Example 12 were examined using the reversed phase high pressure liquid chromatography.

Landscapes

  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne un procédé de production de formes médicamenteuses, contenant des vitamines, obtenues par extrusion d'un polymère fondu contenant des vitamines, suivie d'un formage. L'invention est caractérisée en ce que l'on utilise de l'hydroxypropylcellulose comme matrice polymère.
PCT/EP1996/004272 1995-09-29 1996-09-30 Procede de production de preparations solides contenant des vitamines WO1997012604A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU72833/96A AU7283396A (en) 1995-09-29 1996-09-30 Process for producing solid vitamin preparations

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19536387.6 1995-09-29
DE19536387A DE19536387A1 (de) 1995-09-29 1995-09-29 Verfahren zur Herstellung von vitaminhaltigen festen Zubereitungen

Publications (1)

Publication Number Publication Date
WO1997012604A1 true WO1997012604A1 (fr) 1997-04-10

Family

ID=7773627

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1996/004272 WO1997012604A1 (fr) 1995-09-29 1996-09-30 Procede de production de preparations solides contenant des vitamines

Country Status (5)

Country Link
AU (1) AU7283396A (fr)
DE (1) DE19536387A1 (fr)
HR (1) HRP960436A2 (fr)
WO (1) WO1997012604A1 (fr)
ZA (1) ZA968134B (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003505410A (ja) * 1999-07-23 2003-02-12 バイエル アクチェンゲゼルシャフト 速放性押出物、その製造方法および該押出物から得られる製剤
EP1836902A1 (fr) * 2006-03-23 2007-09-26 Firmenich Sa Particules extrudées et vitreuses de vitamine C
EP2925880B1 (fr) * 2012-11-27 2020-07-01 DSM IP Assets B.V. Procédé pour la production de particules extrudées solides distinctes

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19943501A1 (de) 1999-09-10 2001-03-15 Basf Ag Unterwassergranulation wirkstoffhaltiger Schmelzen
DE10026698A1 (de) 2000-05-30 2001-12-06 Basf Ag Selbstemulgierende Wirkstoffformulierung und Verwendung dieser Formulierung
US8377952B2 (en) 2003-08-28 2013-02-19 Abbott Laboratories Solid pharmaceutical dosage formulation
US8025899B2 (en) 2003-08-28 2011-09-27 Abbott Laboratories Solid pharmaceutical dosage form
EP2463327A3 (fr) 2010-12-10 2015-06-03 Basf Se Procédé de fabrication de granulés comprenant au moins un composant soluble dans l'eau
KR101847947B1 (ko) 2013-03-15 2018-05-28 옵코 아이피 홀딩스 Ⅱ 인코포레이티드 안정화되고 변형된 비타민 ｄ 방출 제형
CN105744847A (zh) 2013-11-15 2016-07-06 帝斯曼知识产权资产管理有限公司 通过热熔挤出获得的略溶化合物的制剂
CN115778979A (zh) * 2015-10-07 2023-03-14 帝斯曼知识产权资产管理有限公司 多维生素挤出物
US20210045427A1 (en) * 2018-03-15 2021-02-18 Dsm Ip Assets B.V. Manufacturing of extrudates having improved microbial quality

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0465338A1 (fr) * 1990-06-29 1992-01-08 Rhone-Poulenc Nutrition Animale Procédé de préparation de granulés de principes actifs par extrusion
WO1996025149A1 (fr) * 1995-02-14 1996-08-22 Basf Aktiengesellschaft Preparations solides de principes actifs, contenant de l'hydroxypropylcellulose
WO1996025151A1 (fr) * 1995-02-14 1996-08-22 Basf Aktiengesellschaft Preparations solides de constituants actifs

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0465338A1 (fr) * 1990-06-29 1992-01-08 Rhone-Poulenc Nutrition Animale Procédé de préparation de granulés de principes actifs par extrusion
WO1996025149A1 (fr) * 1995-02-14 1996-08-22 Basf Aktiengesellschaft Preparations solides de principes actifs, contenant de l'hydroxypropylcellulose
WO1996025151A1 (fr) * 1995-02-14 1996-08-22 Basf Aktiengesellschaft Preparations solides de constituants actifs

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003505410A (ja) * 1999-07-23 2003-02-12 バイエル アクチェンゲゼルシャフト 速放性押出物、その製造方法および該押出物から得られる製剤
EP1836902A1 (fr) * 2006-03-23 2007-09-26 Firmenich Sa Particules extrudées et vitreuses de vitamine C
EP2925880B1 (fr) * 2012-11-27 2020-07-01 DSM IP Assets B.V. Procédé pour la production de particules extrudées solides distinctes

Also Published As

Publication number Publication date
DE19536387A1 (de) 1997-04-03
HRP960436A2 (en) 1998-02-28
AU7283396A (en) 1997-04-28
ZA968134B (en) 1998-03-27

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