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WO1981002521A1 - Composition de vehicule pharmaceutique et son procede de production - Google Patents

Composition de vehicule pharmaceutique et son procede de production Download PDF

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Publication number
WO1981002521A1
WO1981002521A1 PCT/US1980/000235 US8000235W WO8102521A1 WO 1981002521 A1 WO1981002521 A1 WO 1981002521A1 US 8000235 W US8000235 W US 8000235W WO 8102521 A1 WO8102521 A1 WO 8102521A1
Authority
WO
WIPO (PCT)
Prior art keywords
direct compression
compression vehicle
powdered cellulose
dicalcium phosphate
phosphate dihydrate
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/US1980/000235
Other languages
English (en)
Inventor
J Kanig
R Parvez
N Herman
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Mendell Edward Co Inc
Original Assignee
Mendell Edward Co Inc
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 Mendell Edward Co Inc filed Critical Mendell Edward Co Inc
Priority to PCT/US1980/000235 priority Critical patent/WO1981002521A1/fr
Priority to EP19800901982 priority patent/EP0047734A1/fr
Publication of WO1981002521A1 publication Critical patent/WO1981002521A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

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
    • A61K9/2004—Excipients; Inactive ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
    • A61J3/10—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of compressed tablets
    • 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
    • A61K9/2009—Inorganic compounds
    • 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 is directed to pharmaceutical vehicles and a method for producing such vehicles for use in tableting presses.
  • the art is an old one, and while various improvements have been introduced, they have come slowly, and the rapid and efficient production of tablets by the manufacturer of the final product is still subject to many drawbacks.
  • the field is generally referred to as direct compression and an essential element of this direct compression process and formulation is the vehicle which carries the active ingredient or ingredients and forms a major portion of the mass to be tabletec.
  • the media available have generally been single-substance vehicles, such as lactose, cellulose, dicalcium phosphate, dextrose, starch, and sucrose. These vehicles conferred upon the overall formulation certain mechanical attributes of flowability and compactibility. Both properties are absolute essentials in a direct compression vehicle.
  • the most recently developed material in this area has been microcrystalline cellulose.
  • microcrystalline cellulose suffers from certain undesirable features. It has only fair flowability and relatively high hygroscopicity.
  • spray- dried lactose and dextrose change color on standing.
  • Dicalcium phosphate when used as a single component, often cannot incorporate large proportions of non- compressible active ingredients. In general, none of the available materials could meet all the demands of a formulator, i.e., flowability, compressibility, capacity, stability, bioavailability , and economy.
  • powdered cellulose preferably alpha-cellulose, and dicalcium phosphate dihydrate in a roller compactor.
  • a roller compactor such as a Chilsonator
  • the powdered cellulose and dicalcium phosphate dihydrate are blended in a ratio of 85:15 to 15:85. Best compressibility, as measured by tablet hardness, degree of friability, and other desired characteristics, is obtained when the ratio of powdered cellulose to dicalcium phosphate dihydrate is between 85:15 and 50:50 and this is the preferred range. Most preferably, the range is from 70:30 to 60:40.
  • the two materials are preblended and are then fed to a roller compactor, the two rolls haying a particular configuration to allow for compaction of the material.
  • the configuration may be of a concentrically sine curved cavity, such as is shown in U. S. Patent
  • the preblended materials Prior to being fed to the roller compactor, can be, and preferably are, densified in a screw conveyor. This densification involves de-aeration of the powder to permit closer particle-to-particle contact.
  • the blend of powdered cellulose and dicalcium phosphate dihydrate is formed into a compacted sheet.
  • This sheet passes through a breaker bar to permit more manageable flow of the mass into the next stage of processing for particle sizing.
  • the broken sheet of compressed powder is then fed to the comminutor, which may be a Fitzmill, so as to further reduce the broken sheet into particles of a desirable distribution range.
  • the particles are then fed to a screener, or sizing mechanism, so as to separate the product from both fines and oversized materials.
  • the commercial product has a particle size range of from 20 to 600 microns. Preferably, the particle size range is from 70 to 200 microns.
  • the fines from the screening operation can be recycled to the original blending apparatus, while oversized particles are merely returned to the comminutor for further particle sizing and screening.
  • particle size distribution is a critical factor in both desirable properties of flowability and compressibility.
  • the range of particle sizes in any given granulation is instrumental in the performance of the granulation in producing satisfactory compressed tablets. Any major shift in either direction (more fines or mere coarse particles) away from established optimum distribution may result in serious deficiencies in the effectiveness of any particular granulation. Such deficiencies can account for a complete failure of the mass to flow or compress, at one extreme, to other negative attributes such as tablet-to-tablet variations in weight, hardness, and content of active ingredient or ingredients. Any, or all, of these negative results nay account for an inferior product with deficient effectiveness in therapeutic efficacy.
  • the thus obtained product is useful as a direct compression vehicle in tableting with active ingredients. Small amounts of other materials can be added to the blend of powdered cellulose and dicalcium phosphate dihydrate for improved performance in the finally formed pharmaceutical tablet, or to aid in processing.
  • powdered cellulose preferably alpha-cellulose, and dicalcium phosphate dihydrate are blended in particular amounts.
  • the ratio of the two materials is between 85:15 and 15:S5 in order to obtain, from the ultimate directly compressible material, a tablet with a wide range of desirable characteristics.
  • the ratio of powdered cellulose to dicalcium phosphate dihydrate is between 85:15 and 50:50, based, again, on the desired characteristics of a given tablet. Most preferably, the ratio is 70:30 to 60:40.
  • the preferred powdered cellulose material is one whicft is composed of minute fibrous and amorphous cellulose particles which are, preferably, derived from wood pulp.
  • the fibers of this powdered cellulose are, preferably, completely wettable, acting as natural wicks and, when employed in tablet formulation, accelerate tablet disintegration after oral administration.
  • the cellulose useful in this process is. as defined in The united States Pharmacopeia, 20th Edition, 1980, at page 1219 for powdered cellulose.
  • the cellulose employed has a fiber length of 20.-80 microns for best compactibility.
  • Such a material is sold by Edward Mendell Co., Inc., the assignee of this application, under the trademark "REXCEL.”
  • dicalcium phosphate dihydrate The specifications for the dicalcium phosphate dihydrate are as shown in the United States Pharmacopeia, 20th Edition, 1980, at page 112. Such a material is available from Edward Mendell Co., Inc. as "EMCOMPRESS.”
  • the powdered cellulose and dicalcium phosphate dihydrate are blended, in the desired proportions, in a suitable vessel.
  • the materials are first admixed in a blending vessel 1, which may be vibrated by a vibrator 2, to insure better blending and mixing of the materials.
  • the blended cellulose and dicalcium phosphate dihydrate are moved, via a conveyor 3, to a second olending vessel 4. They are conducted from this second blending vessel 4, via a horizontal feeder 5 and an attached vertical feeder 6, to a final hopper or blending vessel 7.
  • the equipment just described for blending of the powdered cellulose and dicalcium phosphate dihydrate, up to the blending vessel or hopper 7, are not critical to the processing of the materials. It is only necessary that these materials be adequately mixed and blended up to this point, and any suitable equipment in the industry can be employed.
  • the blended materials are conducted via a horizontal screw feeder 8 and a vertical screv; feeder 9 to the rolls of a roller compactor 10.
  • This is referred to as a T-feed to the roller compactor and is an essential component of the invention.
  • a densified powder mass is formed. The powder is densified sufficiently for controlled volume flow.
  • the densified powder mass is forced between the two rollers cf a roller compactor.
  • the roller compactor can be of the Chilsonator type, as described in U.S. Patent 3,255,285 - Chilson.
  • the cavities in the two rolls of the roller compactor can be sine curved cavities, or other configurations, as desired.
  • a Chilsonator Model DM roller compactor is operated with a roll pressure of 1G00 to 2000 psi at a roll speed of 6 to 30 rpm.
  • the feed rate to the roller compactor from the T-feed is such that a solid sheet exits froa. the roller compactor. If the material exiting from the roller compactor is powdery, then the rate of feed is increased; if the sheet is too brittle, as indicated by undue strain on the comminutor, then the rate of feed to the roller compactor is decreased.
  • the hardness of this solid sheet is such that the direct compression vehicle ultimately produced has the requisite particle size distribution range and compressibility.
  • the sheet of material is then led through a breaker bar 11, or other apparatus, for reducing the solid sheet of compacted material to a form which is more manageable for screener sizing, such as fragments of a sheet at this stage.
  • the portions of the compacted sheet are fed to a comminutor 12, where the portions are reduced to particles.
  • the comminutor may be of the type known as a Fitzmill.
  • a suitable Fitzmill, operable in the present invention is the one sold by the Fitzpatrick Company of Elmhurst, Illinois, as model DKAS012.
  • the particles formed in the comminutor 12 are fed to a screening apparatus 13. In the screening apparatus, the particles are separated into the desired size range, from 20 to 600 microns.
  • the specific size range to be obtained is based upon the use to which the precompacted, direct compression material is to be put.
  • the particle size range is from 70 to 200 microns. If desired, the oversized particles from the screening can be returned to the comminutor 12 for further processing, while the fines can be returned to blending vessel I for recompaction.
  • certain other materials can be employed in combination with the dicalcium phosphate dihydrate. These materials are non-freeiy flowing, comprised of short fibers, inert, and highly compressible. Such materials include microcrystalline cellulose, soya protein, and certain other fibrous vegetable materials which include bran and dried fruit cellular fiber. These could be employed in certain special circumstances, such as when a nutritional supplement is desired in a tablet base. Frequently, however, such materials are more expensive than the powdered cellulose without a substantial improvement in properties.
  • the flowability of the powdered cellulose, or substitute material is not important.
  • the function of the present process is to transform the materials into compressible agents; it is to take a powder which does not flow, and form it into a flowable material which can be used in a tableting press.
  • Such materials include lactose, calcium sulfate, calcium sulfate dihydrate, calcium carbonate, dextrose and dextrates, and magnesium oxide. Such materials would normally be used for shelf life and compatibility of certain active ingredients.
  • Both the powdered cellulose and dicalcium phosphate dihydrate should have an initial particle size of up to 1,000 microns, mean particle diameter.
  • the conditions employed in the comminutor are varied to accommodate the original particle sizes of the material placed in the blending vessel. For example, screen size, rpm, and rate of feed of the material into the comminutor can be varied.
  • other materials may be added for improvement of specific properties. For example, binders, such as starches, ethylcellulose, guar gum, tragacanth and acacia gum may be added. When added, they are added in levels of up to 25%.
  • lubricants may be added.
  • Such lubricants include materials such as magnesium stearate, calcium stearate, sodium stearate, stearic acid, and other animal and vegetable fatty acids.
  • lubricants are not generally needed, but may be used in amounts of up to 5%.
  • An additional type of material which may be added to the blend is a disintegrant.
  • a disintegrant When the direct compression material is employed for certain active ingredients, the use of a disintegrant is indicated for enhanced dissolution of the ultimate tablet.
  • Materials frequently employed as cisint ⁇ grants include corn, wheat, potato, and rice starches, and their derivatives, along with carboxymethylcellulose.
  • the disintegrant when employed, is usually used in amounts of up. to 25%. It is not a requirement of the compression vehicle and, if added to the direct compression vehicle blend, is done so only to avoid the necessity, if any, for adding it to the end product.
  • the direct compression material formed by the compaction of powdered cellulose and dicalcium phosphate dihydrate has good self- disintegration properties, as indicated, auxiliary disintegrants may not be required in an ultimate tablet formulation.
  • the superior flow properties of the direct compression material formed according to the present invention permit the elimination of powder type glidants.
  • materials which have been routinely used to aid in the flow of prior compression vehicles such materials including fumed silica and other silicon dioxide prccucts.
  • the vehicle should have the following properties:
  • flowability excellent flowability as evidenced by absence of any manifestation of a tendency to bridging or irregular flow pattern that may cause undesirable variation in tablet-to-tablet weight or content.
  • the shape of the particles formed in the direct compression vehicle of the present invention is an irregular sphere. Upon compaction in-e- tablets, this allows for inter-particulate compartments which provide for entrapment of small doses of active ingredients, thus providing for a uniformity in the final blend.
  • a quantity of 65 parts of powdered cellulose was blended with 35 parts dicalcium phosphate dihydrate.
  • the preferred alpha-cellulose, used in this Example, has the following specifications:
  • the blend was fed through conveyors and blending hoppers, in accordance with the broad disclosure of the present invention to a roller compactor.
  • the feed rate of the screw conveyor to the roller compactor was 10 rpm
  • the roll speed of the roller compactor was 6 rpm
  • the pressure in the roller compactor was 1000 psi.
  • the compacted sheet which emanated from the roller compactor was broken by a breaker bar and the material was then milled in a Fitzmill DKAS 012 at 4000 rpm, employing a 0.024 inch round hole perforated plate.
  • the material which had a bulk density of 0.55 g/ml, was sieved, with the following screen retentions:
  • Example 1 the same ratios of materials were blended and processed in the same manner.
  • the bulk density of the resulting material was 0.53 g/ml. and the percent retention was as follows: Screen Size Percent Retained
  • Example 1 the same ratios of materials were blended and processed in the same manner.
  • the bulk density of the resulting material was 0.54 g./ml. and the percent retention was as follows:
  • Example 1 Material of Example 1 with a particle size of 70-200 microns 13-17.5
  • Corn starch was selected as representative of active ingredients which have poor compressibility. The test was repeated employing calcium carbonate in an amount of 50%, with the following results:
  • the direct compression vehicles formed according to the present invention can be tableted with a v/ide variety of active ingredients.
  • the direct compression vehicle of the present invention can be incorporated with any active medicinal agent or food nutrient additive which is non-reactive with the components of the direct compression vehicle and will provide tablets having a wide range of desired properties.
  • active medicinal agent or food nutrient additive which is non-reactive with the components of the direct compression vehicle and will provide tablets having a wide range of desired properties.
  • the materials which can be employed are multivitamins, potassium gluconate, potassium bromate, acetaminophen, and others. The specific properties are dependent on the active ingredient and the use to which it will be put. Many of these are materials which could not be tableted with most previous direct compression vehicles. Such materials include various lactoses and directly compressible sugars and starches.
  • the direct compression vehicle of the present invention can be combined with active ingredients over a broad range. From 10 to 99.9% of the vehicle can effectively be combined with from 90 to 0.1% of active ingredients.
  • Potassium gluconate was combined with the same direct compression vehicle as in Example 8.
  • the tablets were formed on a Manesty Beta Press.
  • the amounts of direct compression vehicle were from 15 to 25%. These tablets had satisfactory hardness for the mechanical stresses experienced in packaging and shipping.

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

Abstract

Un vehicule pharmaceutique permet la compression directe, avec un ingredient actif, dans une machine de fabrication de comprimes pour former un produit pret a l'administration pharmaceutique. Le vehicule pharmaceutique ou excipient est forme par compactage, dans un compacteur a rouleau (10), tel qu'un "Chilsonator", d'un melange, dans des proportions donnees, de cellulose en poudre, de preference de l'alpha cellulose, et du dihydrate de phosphate de calcium double. Le compactage de ces materiaux resulte en une feuille auto-portante qui est un melange compacte des deux materiaux. Cette feuille est brisee, tamisee a la dimension appropriee, et les particules resultantes sont utilisees pour la formation de comprimes avec des ingredients actifs dans une presse de fabrication de comprimes standards. Les comprimes obtenus sont plus facilement formes et presentent une amelioration, inter alia, en ce qui concerne la friabilite, la desintegration, et la dissolution. Des petites quantites d'autres materiaux peuvent etre incorporees avec la cellulose en poudre et le dihydrate de phosphate de calcium double.
PCT/US1980/000235 1980-03-10 1980-03-10 Composition de vehicule pharmaceutique et son procede de production Ceased WO1981002521A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
PCT/US1980/000235 WO1981002521A1 (fr) 1980-03-10 1980-03-10 Composition de vehicule pharmaceutique et son procede de production
EP19800901982 EP0047734A1 (fr) 1980-03-10 1980-03-10 Composition de vehicule pharmaceutique et son procede de production

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
WOUS80/00235 1980-03-10
PCT/US1980/000235 WO1981002521A1 (fr) 1980-03-10 1980-03-10 Composition de vehicule pharmaceutique et son procede de production

Publications (1)

Publication Number Publication Date
WO1981002521A1 true WO1981002521A1 (fr) 1981-09-17

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Country Status (2)

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EP (1) EP0047734A1 (fr)
WO (1) WO1981002521A1 (fr)

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0124027A1 (fr) * 1983-04-29 1984-11-07 FISONS CORPORATION (a Massachusetts corporation) Compositions pharmaceutiques uniformes rapidement solubles et leur préparation
EP0127400A3 (fr) * 1983-05-31 1986-06-11 Stauffer Chemical Company Véhicule contenant de l'oxyde de magnésium pour la fabrication d'un comprimé par compression directe
US4675188A (en) * 1985-08-02 1987-06-23 Stauffer Chemical Company Granular anhydrous dicalcium phosphate compositions suitable for direct compression tableting
EP0193984A3 (en) * 1985-03-08 1987-08-19 Fmc Corporation Coprocessed microcrystalline cellulose and calcium carbonate composition and its preparation
US4707361A (en) * 1985-08-02 1987-11-17 Stauffer Chemical Company Granular anhydrous dicalcium phosphate compositions suitable for direct compression tableting
EP0237241A3 (fr) * 1986-03-06 1988-02-24 American Home Products Corporation Comprimés à base d'un supplément calcique
US4744987A (en) * 1985-03-08 1988-05-17 Fmc Corporation Coprocessed microcrystalline cellulose and calcium carbonate composition and its preparation
US7879382B2 (en) 2005-09-30 2011-02-01 Fmc Corporation Stabilizers and compositions and products comprising same
US7998505B2 (en) 2006-10-27 2011-08-16 Fmc Corporation Dry granulation binders, products, and use thereof
US8329221B2 (en) 2009-11-05 2012-12-11 Fmc Corporation Microcrystalline cellulose and calcium phosphate compositions useful as pharmaceutical excipients
US8632818B2 (en) 2009-11-05 2014-01-21 Fmc Corporation Microcrystalline cellulose and calcium phosphate compositions useful as pharmaceutical excipients
US8632819B2 (en) 2009-12-22 2014-01-21 Fmc Corporation Microcrystalline cellulose and calcium carbonate compositions useful as recompactible pharmaceutical excipients
US8801847B2 (en) 2002-05-14 2014-08-12 Fmc Corporation Microcrystalline cellulose compositions
US8927609B2 (en) 2011-12-09 2015-01-06 Fmc Corporation Co-attrited stabilizer composition
US9055757B2 (en) 2011-10-05 2015-06-16 Fmc Corporation Stabilizer composition of co-attrited microcrystalline cellulose and carboxymethylcellulose, method for making, and uses
US9826763B2 (en) 2011-10-05 2017-11-28 Fmc Corporation Stabilizer composition of microcrystalline cellulose and carboxymethylcellulose, method for making, and uses
US10258576B2 (en) 2004-05-24 2019-04-16 Takeda As Particulate comprising a calcium-containing compound and a sugar alcohol

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2663907A (en) * 1949-02-14 1953-12-29 British Celanese Converting fibrous cellulose into an easily powderable form
US3146168A (en) * 1962-04-10 1964-08-25 Fmc Corp Manufacture of pharmaceutical preparations containing cellulose crystallite aggregates
US3344030A (en) * 1964-06-15 1967-09-26 American Home Prod Reinforced directly compressed nongranulated pharmaceutical crystalline lactose tables
US3357845A (en) * 1963-01-31 1967-12-12 Fmc Corp Shaped articles containing cellulose crystallite aggregates having an average level-off d. p.
US3396226A (en) * 1965-01-06 1968-08-06 Hoffmann La Roche Nongranulated compressed tablets of ascorbic acid with microcrystalline cellulose
US3564083A (en) * 1968-03-27 1971-02-16 Brevets Granofibre Sebreg Soc Formation of fibrous granules
US3883647A (en) * 1972-12-06 1975-05-13 Ives Lab Tablet formulation
US3904726A (en) * 1972-07-21 1975-09-09 Des Brevets Granofibre Sebreg Methods of manufacturing fibrous granulates
US4159345A (en) * 1977-04-13 1979-06-26 Fmc Corporation Novel excipient and pharmaceutical composition containing the same

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2663907A (en) * 1949-02-14 1953-12-29 British Celanese Converting fibrous cellulose into an easily powderable form
US3146168A (en) * 1962-04-10 1964-08-25 Fmc Corp Manufacture of pharmaceutical preparations containing cellulose crystallite aggregates
US3357845A (en) * 1963-01-31 1967-12-12 Fmc Corp Shaped articles containing cellulose crystallite aggregates having an average level-off d. p.
US3344030A (en) * 1964-06-15 1967-09-26 American Home Prod Reinforced directly compressed nongranulated pharmaceutical crystalline lactose tables
US3396226A (en) * 1965-01-06 1968-08-06 Hoffmann La Roche Nongranulated compressed tablets of ascorbic acid with microcrystalline cellulose
US3564083A (en) * 1968-03-27 1971-02-16 Brevets Granofibre Sebreg Soc Formation of fibrous granules
US3904726A (en) * 1972-07-21 1975-09-09 Des Brevets Granofibre Sebreg Methods of manufacturing fibrous granulates
US3883647A (en) * 1972-12-06 1975-05-13 Ives Lab Tablet formulation
US4159345A (en) * 1977-04-13 1979-06-26 Fmc Corporation Novel excipient and pharmaceutical composition containing the same

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4517179A (en) * 1983-04-29 1985-05-14 Pennwalt Corporation Rapid dissolving, uniform drug compositions and their preparation
EP0124027A1 (fr) * 1983-04-29 1984-11-07 FISONS CORPORATION (a Massachusetts corporation) Compositions pharmaceutiques uniformes rapidement solubles et leur préparation
EP0127400A3 (fr) * 1983-05-31 1986-06-11 Stauffer Chemical Company Véhicule contenant de l'oxyde de magnésium pour la fabrication d'un comprimé par compression directe
US4744987A (en) * 1985-03-08 1988-05-17 Fmc Corporation Coprocessed microcrystalline cellulose and calcium carbonate composition and its preparation
EP0193984A3 (en) * 1985-03-08 1987-08-19 Fmc Corporation Coprocessed microcrystalline cellulose and calcium carbonate composition and its preparation
US4675188A (en) * 1985-08-02 1987-06-23 Stauffer Chemical Company Granular anhydrous dicalcium phosphate compositions suitable for direct compression tableting
US4707361A (en) * 1985-08-02 1987-11-17 Stauffer Chemical Company Granular anhydrous dicalcium phosphate compositions suitable for direct compression tableting
EP0237241A3 (fr) * 1986-03-06 1988-02-24 American Home Products Corporation Comprimés à base d'un supplément calcique
US4781925A (en) * 1986-03-06 1988-11-01 American Home Products Corporation Calcium supplement compressed tablets
US8801847B2 (en) 2002-05-14 2014-08-12 Fmc Corporation Microcrystalline cellulose compositions
US10357460B2 (en) 2004-05-24 2019-07-23 Takeda As Particulate comprising a calcium-containing compound and a sugar alcohol
US10258576B2 (en) 2004-05-24 2019-04-16 Takeda As Particulate comprising a calcium-containing compound and a sugar alcohol
US7879382B2 (en) 2005-09-30 2011-02-01 Fmc Corporation Stabilizers and compositions and products comprising same
US7998505B2 (en) 2006-10-27 2011-08-16 Fmc Corporation Dry granulation binders, products, and use thereof
US8932629B2 (en) 2006-10-27 2015-01-13 Fmc Corporation Co-processed microcrystalline cellulose and sugar alcohol as an excipient for tablet formulations
US8632818B2 (en) 2009-11-05 2014-01-21 Fmc Corporation Microcrystalline cellulose and calcium phosphate compositions useful as pharmaceutical excipients
US8329221B2 (en) 2009-11-05 2012-12-11 Fmc Corporation Microcrystalline cellulose and calcium phosphate compositions useful as pharmaceutical excipients
US8632819B2 (en) 2009-12-22 2014-01-21 Fmc Corporation Microcrystalline cellulose and calcium carbonate compositions useful as recompactible pharmaceutical excipients
US9055757B2 (en) 2011-10-05 2015-06-16 Fmc Corporation Stabilizer composition of co-attrited microcrystalline cellulose and carboxymethylcellulose, method for making, and uses
US9826763B2 (en) 2011-10-05 2017-11-28 Fmc Corporation Stabilizer composition of microcrystalline cellulose and carboxymethylcellulose, method for making, and uses
US10299501B2 (en) 2011-10-05 2019-05-28 DuPont Nutrition USA, Inc. Stabilizer composition of microcrystalline cellulose and carboxymethylcellulose, method for making, and uses
US8927609B2 (en) 2011-12-09 2015-01-06 Fmc Corporation Co-attrited stabilizer composition
US9828493B2 (en) 2011-12-09 2017-11-28 Fmc Corporation Co-attrited stabilizer composition having superior gel strength

Also Published As

Publication number Publication date
EP0047734A1 (fr) 1982-03-24

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