US3340152A - Compressed oral drug tablet granulations containing admixed therein about 1% to 15% of polyfluorocarbon type polymer lubricant powders in about 1 to 150 micron particle size - Google Patents

Compressed oral drug tablet granulations containing admixed therein about 1% to 15% of polyfluorocarbon type polymer lubricant powders in about 1 to 150 micron particle size Download PDF

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Publication number
US3340152A
US3340152A US328494A US32849463A US3340152A US 3340152 A US3340152 A US 3340152A US 328494 A US328494 A US 328494A US 32849463 A US32849463 A US 32849463A US 3340152 A US3340152 A US 3340152A
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US
United States
Prior art keywords
tablets
polyfluorocarbon
particle size
tablet
compressed
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.)
Expired - Lifetime
Application number
US328494A
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English (en)
Inventor
Hotko Edward Alexander
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.)
BASF Corp
Novartis Corp
Original Assignee
Ciba Geigy Corp
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Filing date
Publication date
Application filed by Ciba Geigy Corp filed Critical Ciba Geigy Corp
Priority to US328494A priority Critical patent/US3340152A/en
Priority to GB46629/64A priority patent/GB1043639A/en
Priority to FR997342A priority patent/FR1448784A/fr
Priority to BE656685A priority patent/BE656685A/xx
Priority to NL6414134A priority patent/NL6414134A/xx
Application granted granted Critical
Publication of US3340152A publication Critical patent/US3340152A/en
Anticipated expiration legal-status Critical
Expired - Lifetime 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
    • 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
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates

Definitions

  • lubricating agents In the manufacture of tablets, the addition of lubricating agents is necessary 1) to facilitate the flow of the granulate mixture, (2) to reduce the friction between the granulate and the die during compression and ejection of the compressed tablets, and (3) to prevent the sticking of the compressed tablet to the faces of the punches.
  • Compounds useful as lubricants are required to have high melting points, be chemically inert and physiologically non-toxic, and should affect neither the physiologically active ingredient, nor, at least not to a great degree, the physical characteristics of the compressed tablet, such as its disintegration time, its hardness and the like.
  • lubricants tend to alter the characteristics of the tablets; specifically they prolong the disintegration time and decrease the hardness of the tablet.
  • certain lubricants such as the widely used salts of stearic acid, e.g. sodium stearate, magnesium stearate, calcium stearate and the like, as well as hydrogenated castor oil, sodium lauryl sulfate, polyethylene glycols, powdered edible vegetable oils, and the like, cause a. marked and undesired increase of the disintegration time of the tablet.
  • certain lubricants, particularly magnesium stearate tend to soften the tablets.
  • lubricants have individual disadvantages. For example, while it was found to be a lubricant devoid of any significant effects on the disintegration time of the tablets, stearic acid, due to its acidic properties, has other disadvantages; for example, it cannot be used in tablets containing physiologically active materials which are easily hydrolyzed, such as reserpine, without impairing the stability of the drug. Even its metal salts are incompatible With certain ester compounds, e.g. aspirin, which is hydrolyzed in the presence of a metal stearate. Polyethylene glycol lubricants are, for example, not suitable for tablets containing syrosingopine.
  • a further object of the present invention is to provide the use in the process of manufacturing tablets of a lubricating agent which is chemically inert and physiogically non-toxic, and which does not substantially alter the desired physical characteristics of the compressed tablet.
  • the primary object of this invention is in the process of manufacture of tablets, the step which comprises using a polymer of the polyfluorocarbon type or a mixture of polymers of the polyfluorocarbon type as the lubricating agent.
  • polymers of the polyfluorocarbon type i.e. the so-called polyfluorocarbons or fluorocarbon polymers
  • polyfluorocarbons or fluorocarbon polymers have the characteristics necessary of the lubricating agents used in manufacturing tablets, i.e. they facilitate the flow of the granulation mixture, they reduce the friction between the granulation and the die during compression, they prevent the compressed tablet from sticking to the face of the punches, and they reduce the force necessary to eject it after compression.
  • polymers of the polyfluorocarbon type have a sufliciently high melting point and are chemically inert; they are, therefore, compatible with tablet ingredients which are easily degraded in the presence of known lubricating material, and do not pose any physiologic and toxic problems.
  • the polymeric substances of the polyfluorocarbon type when used as lubricating agents, affect the physical characteristics of the compressed tablet to a much smaller degree than the majority of the known lubricants.
  • the disintegration time of a tablet containing as a lubricant a polymer of the polyfluorocarbon type is smaller than that of a tablet containing as a lubricating agent a metal stearate lubricant, e.g. magnesium stearate and the like, or hydrogen castor oil.
  • Polymers of the polyfluorocarbon type are a well-known group of polymeric and copolymeric substances made up of carbon and fluorine, which, in addition, may contain hydrogen and/or chlorine.
  • Particularly useful as a lubricating agent is the polytetrafluoroethylene of the formula (-CF -CF other polyfluorocarbons, capable of being used'as lubricants in the process of manufacturing tablets according to this invention, are the copolyrner of tetrafluoroethylene and hexafluoropropylene of the formula the polyvinylidene fluoride of the formula the copolymer of vinylidene fluoride and hexafluoropropylene of the formula (C F2CHz-C F2?
  • the tablets manufactured with the help of such lubricating agent(s) have a content from about 1 percent to about 15 percent, preferably from about 2 percent to about percent, of the polymer(s) of the polyfluorocarbon type.
  • tablets containing as the lubricating agent a polymer of the polyfluorocarbon type or a mixture of polymers of the polyfluorocarbon type.
  • the tablets contain the usual bulking materials, such as sugars, e.g. lactose, glucose, sucrose and the like, inorganic salts, e.g. calcium phosphate, calcium sulfate, calcium lactate and the like, or any other suitable bulking materials, disintegrants, such as starches, e.g. corn starch, wheat starch, rice starch and the like, alginic acid or salts thereof, e.g.
  • sugars e.g. lactose, glucose, sucrose and the like
  • inorganic salts e.g. calcium phosphate, calcium sulfate, calcium lactate and the like
  • disintegrants such as starches, e.g. corn starch, wheat starch, rice starch and the like, alginic acid or salts thereof, e.g.
  • ammonium or calcium alginate and the like microcrystalline cellulose and the like or any other suitable material enhancing the disintegration of a tablet, as well as any other ingredients facilitating the manufacture of a tablet or its use, such as water-repellents, coloring agents, and the like.
  • the tablets are prepared according to standard methods of tablet manufacturing, usually by forming a granulate mixture suitable for compression.
  • the polymer(s) of the polyfluorocarbon type used as lubricant(s) is(are) added to the mixture of the tablet ingredients either before granulation or after the granulate has been formed.
  • the granulate is prepared by mixing the physiologically active product(s), the bulking material(s), the disintegrant(s), or any other ingredients, and, if desired, the
  • the wet mass is then passed through a mill to reduce the particle size, dried to lower the moisture content, and, if necessary, again passed through a mill.
  • Formation of the granules can also be achieved by the slugging method, i.e. by blending the physiologically active ingredient(s), the bulking agent(s), the disintegrant(s), or any other ingredients, and, if desired, the polymer(s) of the polyfluorocarbon type used as the lubricant(s), all having the desired particle size, in a suitable mixer, agglomerating the powder mass by slugging it or passing it through a compactor mill, and, if necessary, classifying the agglomer ated mass or passing it through a grinder.
  • the granulate does not yet contain the polymer(s) of the polyfluorocarbon used as the lubricant(s), the latter is(are) mixed with the granulate mixture, which is then compressed into the desired tablets.
  • the resulting tablets may be used as such, or, if desired, may be coated; coatings may have non-enteric (sugar, methylcellulose, sodium carboxy-methylcellulose coatings and the like) or enteric properties (cellulose acetate phthalate, polyvinyl acetate coatings and the like), and may be applied by the pan coating or compression coating method.
  • a coating granulate mixture may be utilized which has from about 1 percent to about percent, preferably from about 2 percent to about 10 percent, of the lubricating agent(s).
  • Example 1 Tablets each containing 0.05 g. of 2-[N-benzyl-N-(2- N,N-dimethylarninoethyl)-amino] pyridine hydrochloride as the active ingredient, and 0.01 g. of polytetrafluoroethylene of an average particle size of from about 5 microns to about 10 microns, as the lubricating agent, are prepared as follows (for 5,000 tablets).
  • Alcohol 3A 50 percent, q.s.
  • Example 2 Tablets each containing 0.005 g. of methyl a-phenyl-a- (2-piperidyl) -acetate hydrochloride as the physiologically active ingredient, and 0.005 g. of polytetrafluoroethylene of an average particle size' of from about 5 microns to about 10 microns as the lubricating agent, are prepared as follows (for 10,000 tablets).
  • Alcohol 3A 50 percent, q.s.
  • the methyl a phenyl-a-(Z piperidyl)-acetate hydro- V chloride, the corn starch, the lactose and the polytetrafluoroethylene are passed through a 30 mesh screen and the powders are blended in a suitable mixer for thirty minutes.
  • the granulate isformed by adding the alcohol (3A, 50 percent); the wet mass is passed through a No. 12 mesh screen and then dried at 40.
  • the dried granules are broken through a 20 mesh screen and compressed into tablets weighing 0.1 g. using inch standard concave punches.
  • Alcohol 3A 50 percent, q.s.
  • the 6 chloro 7 sulfamyl 2H 3,4-dihydr'o-1,2,4- benzothiadiazine-l,l-dioxide,the corn starch, the lactose and the polytetrafluoroethylene are passed through a 30 mesh screen and the powders are blended in a suitable mixture for thirty minutes.
  • the granulate is. formed by adding the alcohol (3A, 50 percent); the wet mass is passed through a No. 12 mesh screen and then dried at 40.
  • the dried granules are broken through a 20 mesh screen and compressed into tablets weighing 0.2 g. using inch standard concave punches.
  • the polytetrafluoroethylene lubricant can be replaced by an equivalent amount of any other polyfluorocarbon powder, such as the copolymer of tetrafluoroethylene and hexafluoropropylene, polyvinylidene fluoride, polytrifiuorochloroethylene, and the like, as well as by an equivalent amount of a mixture of polytetrafluoroethylene and the copolyrner of tetrafluoroethylene and hexafluoropropylene.
  • any other polyfluorocarbon powder such as the copolymer of tetrafluoroethylene and hexafluoropropylene, polyvinylidene fluoride, polytrifiuorochloroethylene, and the like, as well as by an equivalent amount of a mixture of polytetrafluoroethylene and the copolyrner of tetrafluoroethylene and hexafluoropropylene.
  • Example 4 Compression coated tablets, each containing 0.01 g. of l-hydrazino-phthalazine hydrochloride as the physiologically active ingredient, and, as a lubricating agent, 0.005 g. of polytetrafluoroethylene in the core, the average particle size of the polytetrafluoroethylene being from about 5 microns to about microns, are prepared as follows (for 10,000 tablets).
  • the l-hydrazino-phthalazine hydrochloride, the lactose, the corn starch and the polytetrafluoroethylene are sifted through a 20 mesh sieve and mixed for twenty minutes.
  • the resulting mixture is granulated with the 50 percent ethanol 3A; the granulate is passed through a 12 mesh sieve, dried at about 38 C. and broken through a 20 mesh screen.
  • the coating formulation Weighing 0.2 g., and using 5, inch standard concave punches.
  • the total weight of the tablet is 0.3 g.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
US328494A 1963-12-06 1963-12-06 Compressed oral drug tablet granulations containing admixed therein about 1% to 15% of polyfluorocarbon type polymer lubricant powders in about 1 to 150 micron particle size Expired - Lifetime US3340152A (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
US328494A US3340152A (en) 1963-12-06 1963-12-06 Compressed oral drug tablet granulations containing admixed therein about 1% to 15% of polyfluorocarbon type polymer lubricant powders in about 1 to 150 micron particle size
GB46629/64A GB1043639A (en) 1963-12-06 1964-11-16 Lubricants for compression tabletting
FR997342A FR1448784A (fr) 1963-12-06 1964-12-04 Procédé de préparation de comprimés
BE656685A BE656685A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) 1963-12-06 1964-12-04
NL6414134A NL6414134A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) 1963-12-06 1964-12-04

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US328494A US3340152A (en) 1963-12-06 1963-12-06 Compressed oral drug tablet granulations containing admixed therein about 1% to 15% of polyfluorocarbon type polymer lubricant powders in about 1 to 150 micron particle size

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US3340152A true US3340152A (en) 1967-09-05

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US328494A Expired - Lifetime US3340152A (en) 1963-12-06 1963-12-06 Compressed oral drug tablet granulations containing admixed therein about 1% to 15% of polyfluorocarbon type polymer lubricant powders in about 1 to 150 micron particle size

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US (1) US3340152A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html)
BE (1) BE656685A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html)
GB (1) GB1043639A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html)
NL (1) NL6414134A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3932614A (en) * 1972-02-02 1976-01-13 Fabalon, Inc. Method of lubricating or softening the skin
US4087517A (en) * 1974-10-21 1978-05-02 Charles L. Wragg, Jr. Method of dry lubricating the skin
US4405486A (en) * 1981-08-31 1983-09-20 Warner-Lambert Company Method for preparing granulated perborate salts containing a polymeric fluorocarbon
US4409118A (en) * 1981-04-03 1983-10-11 Warner-Lambert Company Tablet forming cleanser composition and method of preparation
EP0102419A1 (en) * 1982-08-25 1984-03-14 Warner-Lambert Company A granulated perborate salt product, and process for producing the same
USRE32771E (en) * 1983-04-22 1988-10-25 Warner-Lambert Company Denture cleaner having improved dissolution time and clarity and method of preparation
US4844908A (en) * 1986-11-27 1989-07-04 Duphar International Research B.V. Method of preparing tablets with clovoxamine fumarate and tablets thus prepared
EP0253772A3 (en) * 1986-07-15 1989-07-19 Warner-Lambert Company Denture cleansing and/or washing compositions containing a bleach activator

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4034035A (en) * 1975-07-14 1977-07-05 Merck & Co., Inc. Method of preparing multi-toned tablets

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2552027A (en) * 1948-01-17 1951-05-08 American Cyanamid Co Casting gelatin tablets
US2573639A (en) * 1949-12-02 1951-10-30 Myron A Coler Manufacture of porous articles from trifluorochloroethylene polymer
US2936301A (en) * 1956-11-15 1960-05-10 Du Pont Polytetrafluoroethylene granular powders
US2939178A (en) * 1958-04-30 1960-06-07 Continental Diamond Fibre Corp Process for molding sintered polytetrafluoroethylene articles
US3004294A (en) * 1958-03-12 1961-10-17 Hoechst Ag Process for the manufacture of granular products
US3042531A (en) * 1959-12-09 1962-07-03 Leslie Salt Company Method of making a compressed tablet
US3096248A (en) * 1959-04-06 1963-07-02 Rexall Drug & Chemical Company Method of making an encapsulated tablet
US3247066A (en) * 1962-09-12 1966-04-19 Parke Davis & Co Controlled release dosage form containing water-swellable beadlet
US3260774A (en) * 1963-01-21 1966-07-12 Tensolite Insulated Wire Co In Method for the continuous extrusion of unsintered polytetrafluoroethylene powder
US3312764A (en) * 1964-10-22 1967-04-04 Haveg Industries Inc Cold powder molding of polytetrafluoroethylene

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2552027A (en) * 1948-01-17 1951-05-08 American Cyanamid Co Casting gelatin tablets
US2573639A (en) * 1949-12-02 1951-10-30 Myron A Coler Manufacture of porous articles from trifluorochloroethylene polymer
US2936301A (en) * 1956-11-15 1960-05-10 Du Pont Polytetrafluoroethylene granular powders
US3004294A (en) * 1958-03-12 1961-10-17 Hoechst Ag Process for the manufacture of granular products
US2939178A (en) * 1958-04-30 1960-06-07 Continental Diamond Fibre Corp Process for molding sintered polytetrafluoroethylene articles
US3096248A (en) * 1959-04-06 1963-07-02 Rexall Drug & Chemical Company Method of making an encapsulated tablet
US3042531A (en) * 1959-12-09 1962-07-03 Leslie Salt Company Method of making a compressed tablet
US3247066A (en) * 1962-09-12 1966-04-19 Parke Davis & Co Controlled release dosage form containing water-swellable beadlet
US3260774A (en) * 1963-01-21 1966-07-12 Tensolite Insulated Wire Co In Method for the continuous extrusion of unsintered polytetrafluoroethylene powder
US3312764A (en) * 1964-10-22 1967-04-04 Haveg Industries Inc Cold powder molding of polytetrafluoroethylene

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3932614A (en) * 1972-02-02 1976-01-13 Fabalon, Inc. Method of lubricating or softening the skin
US4087517A (en) * 1974-10-21 1978-05-02 Charles L. Wragg, Jr. Method of dry lubricating the skin
US4409118A (en) * 1981-04-03 1983-10-11 Warner-Lambert Company Tablet forming cleanser composition and method of preparation
EP0102418A1 (en) * 1981-04-03 1984-03-14 Warner-Lambert Company Effervescent cleansing composition, and tablets formed of the same
US4405486A (en) * 1981-08-31 1983-09-20 Warner-Lambert Company Method for preparing granulated perborate salts containing a polymeric fluorocarbon
EP0102419A1 (en) * 1982-08-25 1984-03-14 Warner-Lambert Company A granulated perborate salt product, and process for producing the same
USRE32771E (en) * 1983-04-22 1988-10-25 Warner-Lambert Company Denture cleaner having improved dissolution time and clarity and method of preparation
EP0253772A3 (en) * 1986-07-15 1989-07-19 Warner-Lambert Company Denture cleansing and/or washing compositions containing a bleach activator
US4844908A (en) * 1986-11-27 1989-07-04 Duphar International Research B.V. Method of preparing tablets with clovoxamine fumarate and tablets thus prepared

Also Published As

Publication number Publication date
GB1043639A (en) 1966-09-21
NL6414134A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) 1965-06-07
BE656685A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) 1965-06-04

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