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WO1998003064A1 - Composition desintegrante pour solides dispersibles - Google Patents

Composition desintegrante pour solides dispersibles Download PDF

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Publication number
WO1998003064A1
WO1998003064A1 PCT/US1997/012183 US9712183W WO9803064A1 WO 1998003064 A1 WO1998003064 A1 WO 1998003064A1 US 9712183 W US9712183 W US 9712183W WO 9803064 A1 WO9803064 A1 WO 9803064A1
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WIPO (PCT)
Prior art keywords
disintegrant
composition
super
cross linked
active agent
Prior art date
Application number
PCT/US1997/012183
Other languages
English (en)
Inventor
Edward K. Sullivan
Original Assignee
Fmc Corporation
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 Fmc Corporation filed Critical Fmc Corporation
Priority to AU37265/97A priority Critical patent/AU3726597A/en
Priority to EP97934137A priority patent/EP0918456A1/fr
Publication of WO1998003064A1 publication Critical patent/WO1998003064A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/12—Powders or granules
    • A01N25/14—Powders or granules wettable
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/34—Shaped forms, e.g. sheets, not provided for in any other sub-group of this main group
    • 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
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • 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
    • 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
    • A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D17/00—Detergent materials or soaps characterised by their shape or physical properties
    • C11D17/0047—Detergents in the form of bars or tablets
    • C11D17/0065—Solid detergents containing builders
    • C11D17/0073—Tablets
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
    • C11D3/02—Inorganic compounds ; Elemental compounds
    • C11D3/12—Water-insoluble compounds
    • C11D3/124—Silicon containing, e.g. silica, silex, quartz or glass beads
    • C11D3/1246—Silicates, e.g. diatomaceous earth
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
    • C11D3/02—Inorganic compounds ; Elemental compounds
    • C11D3/12—Water-insoluble compounds
    • C11D3/124—Silicon containing, e.g. silica, silex, quartz or glass beads
    • C11D3/1246—Silicates, e.g. diatomaceous earth
    • C11D3/128—Aluminium silicates, e.g. zeolites

Definitions

  • compositions and methods for preparing and using the same which compositions are useful as rapid disintegrants for water-dispersible solid dosage forms of active agents. More particularly, this invention relates to compositions comprising super disintegrants and co-disintegrants useful as excipients for pharmaceutical, agricultural, food, industrial, household and like commercially useful active compounds in solid dosage form which desirably should disintegrate rapidly when placed in an aqueous environment. Compositions containing this novel disintegrant and an active agent, optionally with additives, is also encompassed by this invention.
  • solid dosage forms in which the ingredients, i.e. , active agents, excipients, adjuvants, etc. are processed into various forms such as tablets, briquettes, pellets, granules, and the like.
  • excipients are the disintegrants, and particularly super disintegrants, such as croscarmellose or the like further described below.
  • the solid dosage forms made with these super disintegrants are durable and stable yet readily disintegrate when added to an aqueous medium with concomitant release of the active components.
  • compositions combining a highly effective primary disintegrant (also referred to as super disintegrant) with a co-disintegrant compositions which are at least as effective as super disintegrants but which are much less costly, in which the co-disintegrant synergizes the disintegrant properties of the primary disintegrant.
  • the quantity super disintegrants necessary to rapidly disintegrate water-dispersible, solid dosage forms containing active agents may be substantially reduced, while at the same time maintaining or increasing the rate of disintegration, by substituting for a portion of the super disintegrant a co-disintegrant comprising a diatomaceous earth, a hydrophilic zeolite or a combination thereof to obtain a disintegration rate at least equal to, but preferably greater than that of the super disintegrant alone.
  • a disintegration rate increase can be achieved by simply adding minor amounts of co-disintegrant to a constant amount of super disintegrant. Substitution of the co-disintegrant for super disintegrant, is, however, preferred.
  • the weight percent of co-disintegrant which may be substituted for the more costly super disintegrants in this invention is not a fixed range, but rather may be adjusted to optimize either cost or disintegration rate, or both.
  • the weight percent of the combined super disintegrant and co-disintegrant which may be used in the total weight of any formulation is about 0.05 wt. % to about 10 wt% , preferably about 0.5-3.0 wt.
  • the co-disintegrant alone expressed as a weight percent of the total composition, may comprise from about 0.01 to 9.0 wt% . preferably about 0.1 to 2.7 wt%; and that the weight percent of the super disintegrant may comprise from about 0.045 to 8.0 wt% , preferably about 0.045 to 2.4 wt% .
  • the weight ratio of super disintegrant to co-disintegrant in the disintegrant combination may range from about 4: 1 to about 1 : 10, preferably 3: 1 to 1 :5. and most preferably about 2: 1 to 1 : 1. That is to say, expressing it somewhat differently, as much as about 25 to 90 wt. %, preferably about 25 to 85 wt% , and more preferably about 33 to 50 wt% , of the amount of super disintegrant ⁇ r se which is necessary for sufficient disintegration may be replaced in the combination of this invention by co-disintegrant by virtue of this discovery.
  • composition of the invention may readily be prepared by combining the super disintegrant with the co-disintegrant in any suitable manner for mixing paniculate materials, including dry blending, granulation, or the like. Such mixing techniques are well known in the art.
  • Solid formulations are then prepared by mixing the blended components with the desired active agent plus, if desired, any ancillary ingredients, and the resulting mixture processed to include the desired forms such as tablets, pellets, beads, granules, balls, bars, disks and briquettes. Wettable powders, which do not require disintegrants, are excepted.
  • formulations may be produced from the blend of disintegrants and active agent by any of various known processes, including compression, roller compaction, wet granulation, extrusion, spheronization, and/or pan granulation.
  • dry granulation When tableting is the method selected for producing the solids, conventional dry granulation, wet granulation, direct compression, spheronization or spray drying may be used to prepare the blend for tableting.
  • the selection of method depends primarily on the active agent, the ability of the mixture of the disintegrants and active agent to flow freely in the tableting machine or extruder, and the cohesiveness of the ingredients. If the active agent can be admixed with the disintegrants to produce a free flowing, dense powder, the mixture can be directly compressed.
  • dry granulation a dry powdery blend of the components is compressed to form slugs if a tablet press is used. Alternatively, the dry blend is roller compacted into sheets. The slugs or sheets are then sieved to form densified granules for final tableting.
  • the hardness of the resulting tablet, granule, etc. can be determined routinely by the formulator depending upon the amount and type of additives employed and the degree of pressure in, e.g., the tableting machine.
  • the degree of hardness may affect the disintegration rate, but as shown in Example 4 the increase in disintegration time is not greatly affected by increasing hardness.
  • tablets should be hard enough to resist chalking and/or breaking during normal handling but readily disintegrate in an aqueous medium.
  • the super disintegrants which may be employed in this invention include such compounds as croscarmellose sodium (Ac- Di-Sol , FMC Corp., Philadelphia, PA.), crospovidone, sodium starch glycolate, and the like, or combinations thereof. See Handbook of Pharmaceutical Excipients, 2 nd Ed. , American Pharmaceutical Association, pp. 141 et seq. (1994). Of these, croscarmellose sodium is preferred. Chemically, it will be seen that each of these compounds represents examples of a wholly or partially cross-linked compound such as a cross-linked cellulose or carboxymethyl cellulose , a cross-linked polymer, and a cross-linked starch, respectively. Also, other alkali metal salts may be substituted for the sodium salts generally employed in these materials.
  • the co-disintegrant employed as the second component in the disintegrant composition of this invention are water- insoluble, but highly hydrophilic materials which include not only well-known natural diatomaceous silica (i.e., kieselguhr or infusorial earth), but also such materials as synthetic hydrous calcium silicate prepared by the hydrothermal reaction of natural diatomaceous silica and lime, in which the lime content may range from 20 to 50 wt. %, usually about 26 wt% (e.g. , Micro-Cel , sold by Manville Corp., Denver Colo.) In addition to lime there may also be used magnesium compounds as well as other alkaline earth elements in the preparation of these synthetic materials. Of these silicas the synthetic calcium silicate is preferred.
  • the co-disintegrant may also be a hydrophilic zeolite, preferably one with large open pore structure for channeling of water into a compressed tablet.
  • the co-disintegrant it should be noted, as shown by the examples, should have minimal disintegrant properties when employed alone.
  • the active agents to be delivered with the disintegrants of the invention include any liquids adsorbed on appropriate solids, semi-solids or solid compounds, or mixtures of compounds which are to be eventually dispersed or dissolved in an aqueous medium including agricultural sprays, an industrial process or waste stream, a body of water such as a river or lake, a swimming pool, an oil well, a body fluid, an aqueous food, food supplement or pharmaceutical, or the like.
  • the active agent must not be reactive with the properties of the blend.
  • the solid forms of the invention therefore, have application to a wide variety of fields and products, including agricultural and veterinary products, pharmaceuticals, animal and human foods, swimming pool additives, industrial biocides for oil wells and other applications, cosmetics, household pesticides, industrial and laundry detergents, and dye manufacturing.
  • the amount of active agent is not critical and thus can range broadly from about 10 to 95 wt% of the total composition, with the balance comprising the disintegrant of this invention plus, additives, adjuvants, etc. , if any. Necessarily this amount may encompass e.g. materials ranging from pharmaceutical to agricultural materials, etc. , plus necessary additives and adjuvants, and thus a large variation in amounts must be determined by those skilled in each different art. It follows from this, that the amount of disintegrant of this invention must also vary significantly depending on the nature and amount of said active agent and other additives and adjuvants, if any.
  • the active agents include pesticides such as herbicides, insecticides, fungicides, plant growth regulators, fertilizers and biocides of all types.
  • the pesticides include atrazine, benazone, bromoxynal, trifluralin, propanil, metribuzin, alachlor, butachlor, bromoxynil, clomazone, oxadiazon, whatsoeverban, bifenox, aldicarb, monocrotophos, propoxur, diflubenzuron, carbofuran, permethrin, carbonyl, cypermethrin, endosulfan, cyfluthrin, bifenthrin, terbufos, fenamiphos, cadusafos, paclobutrazol, glyphosine, giberellic acid, glycophosphate, phenylurea, and the like.
  • this amount is not critical and may comprise as much as a major proportion by weight i.e. , in excess of 50 wt% of the total formulation thus, in practice, the choice of additive and amount are matters of routine consideration and trial for the skilled formulator. depending on the nature of the active agent.
  • lubricants facilitate the ejection of compacted forms from a die cavity. They may also reduce interparticle friction and prevent adhesion of materials to die and punch surfaces.
  • Typical lubricants are talc; long chain fatty acid esters or salts thereof such as stearic and palmitic acids, and magnesium or calcium stearate; and the like.
  • Glidants are limited to improvement of the flow properties of powders and granules, and include materials such as aerogenic silica, fumed silicon dioxide and silica hydrogel.
  • disintegrants such compounds as guar gum, magnesium aluminum silicate, copolymers of methacrylic acid with divinylbenzene, potassium alginate, starch, and pregelatinized starch as additives to supplement the above super disintegrants.
  • binders/fillers as dicalcium phosphate, Starch 1500 (sold by National Starch Co. , Bridgewater N.J.),
  • lactose, and microcrystalline cellulose (MCC) compositions for example.
  • MCC carboxymethyl cellulose
  • Lattice ® NT 200, which is microcrystalline cellulose alone.
  • Dispersants may be employed to further break down disintegrated aggregates to primary particle size, and include such materials as naphthalene condensates, ligno-sulfonates, poly aery lates, and phosphate esters.
  • the compounds are generally not applied full strength but are typically applied as formulations which may be applied as such or further diluted for application.
  • Typical formulations include, for example, dust and granule compositions containing the active ingredient in combination with one or more agriculturally acceptable adjuvants, carriers or diluents, preferably with a surface active agent, and optionally with other active ingredients.
  • the choice of formulation depends, of course, on the type of pest and environmental factors present at the particular locus of infestation.
  • the active ingredient of a typical agricultural formulation may, for example, comprise 0.01 percent to 1 percent up to about 90 or 95 percent by weight, preferably 1 percent up to 90 or 95 percent by weight, of the formulation.
  • Agriculturally acceptable carriers, diluents, adjuvants, surface active agents, and optionally other suitable active ingredients comprise the balance of the formulation.
  • a typical formulation may contain from 0.01 to 95 (preferably 1 to 95) percent by weight active ingredient, from 0 to 30 percent by weight surface active agent, and from 5 to 99.99 (preferably 5 to 99) percent by weight of an inert agriculturally acceptable carrier or diluent.
  • Granules for agricultural use, for example, are solid or dry compositions of active ingredient compressed, deposited, or agglomerated to form large particles.
  • Granules usually have an average particle size in the range of 150 to 5000 microns, typically 425 to 850 microns.
  • Granular formulations generally contain from 1 to 50 percent by weight of one or more of the surface active agents described above, and from 50 to 98 percent by weight of one or more of the inert solid or dry carriers or diluents described above.
  • Granules may be produced by agglomeration of dusts or powders, by compaction, by extrusion through a die, or by use of a granulation disk.
  • novel compositions of this invention provide not only a rapid rate of disintegration of the solids at significant cost savings for super disintegrants, but also, particularly in the pharmaceutical field, flexibility in dosage form design. Furthermore, chemically incompatible actives, such as tablets containing several different pesticides or combinations of herbicides and pesticides, can be separated in the solid dosage forms by forming multilayers using known techniques.
  • the disintegrant composition of this invention may, as stated above, be incorporated into conventional pharmaceutical preparations such as tablets (e.g. compressed tablets which may be coated, as with sugar paste).
  • the active agent may be present in admixture with a pharmacologically acceptable solid carrier; for example it may be a solid such as corn starch.
  • a pharmacologically acceptable solid carrier for example it may be a solid such as corn starch.
  • the dosage to be employed may be determined by routine experimentation well known in the art.
  • the active agent may be administered in combination with other drugs together with the novel disintegrant excipient.
  • Examples 1-7 show that synthetic, hydrous calcium silicate works effectively with croscarmellose sodium, sodium starch glycolate, and crospovidone three of the materials referred to above as 'super disintegrants', in increasing the disintegration rate.
  • Example 8 illustrates that comparable results may be obtained with natural diatomaceous earth. It will be noted that the combinations in the examples that included croscarmellose sodium were most effective.
  • examples 1 through 4 are representative of a vitamin formulation, such as niacinamide.
  • agricultural chemicals such as pesticides are frequently tableted to produce unit doses that need only to be placed in a specified volume of water prior to application.
  • Example 5 is intended to exemplify the use of this disintegrant combination in an agricultural pesticide formulation, since ferrous sulfate is listed as a selective herbicide to control broadleaf weeds.
  • Industrial uses would include, for example, detergents such as are shown in examples 6 and 7, or granular fertilizers, which could be formulated routinely by those skilled in the art.
  • Example 9 illustrates the use of a hydrophilic zeolite as a co-disintegrant.
  • the additives include binders, such as microcrystalline cellulose, starch and/or lactose, lubricants such as magnesium stearate and/or stearic acid, and fillers such as dicalcium phosphate.
  • binders such as microcrystalline cellulose, starch and/or lactose
  • lubricants such as magnesium stearate and/or stearic acid
  • fillers such as dicalcium phosphate.
  • Example 2 By the method of Example 1 , 50 grams (25 wt %) of niacinamide, 140 grams (70 wt %) of dicalcium phosphate, 1.0 gram (0.5 wt %) of sodium starch glycolate, 4.0 grams (2.0 wt %) of synthetic diatomaceous silica, 4.0 grams (2.0 wt %) of stearic acid, and 1.0 gram (0.5 wt %) of magnesium stearate were combined and compressed into tablets weighing 775 mg. The properties of these tablets were measured as described in Example 1. Table 2 shows the formulations corresponding to those in Table 1 with the sodium starch glycolate replacing croscarmellose sodium.
  • Example 2a is a formulation of the invention, and Examples 2b-2d are comparative examples.
  • Example 1 By the method of Example 1, 50 grams (25 wt %) of niacinamide, 140 grams (70 wt %) of dicalcium phosphate, 1.0 gram (0.5 wt %) of crospovidone, 4.0 grams (2.0 wt %) of synthetic diatomaceous silica, 4.0 grams (2.0 wt %) of stearic acid, and 1.0 gram (0.5 wt %) of magnesium stearate were combined and compressed into tablets weighing 775 mg. The properties of these tablets were measured as described in Example 1. Table 3 shows the formulations corresponding to those in Table 1 with the crospovidone replacing croscarmellose sodium.
  • Example 3a is a formulation of the invention, and Examples 3b-3d are comparative examples.
  • the blended material was then compressed into tablets weighing 1750 mg on a Stokes single station F press fitted with 15.9 mm (0.625 inch) flat- faced, beveled-edge tooling.
  • the compression forces were varied to produce tablets having tablet hardness of 4, 8, and 12 Kp, respectively.
  • Twenty- four hours after compression hardness was measured for six tablets at each compression force.
  • disintegration tests were performed using USP 701 XXII apparatus. These tests were done in 37 °C distilled water. The average disintegration time for six tablets at each hardness was determined.
  • a control formulation was prepared in which croscarmellose sodium was the only disintegrant incorporated.
  • Example 4a is a formulation of the invention
  • Example 4b is the comparative example.
  • the granule sizes ranged from 425-1180 microns. These granules were described as being very durable.
  • the disintegration time of the granules was determined by the method of USP 701 XXII using a 100 mesh screen. A 5 gram sample of the granules was placed in the basket which was immersed in 37°C distilled water. The disintegration time of this sample was 1.1 minutes. This description is specific to Example 5a, but the same procedure was followed for Examples 5b-5d. Table 5 shows the formulations corresponding to those in Table 1 , i.e. Example 5a is an example of the invention, and Examples 5b-5d are comparative examples.
  • Alconox Detergent powder Alconox, Inc. , New York, NY 10003
  • Alconox Detergent powder Alconox, Inc. , New York, NY 10003
  • an alkaline detergent comprising a blend of sulfates, phosphates, and carbonates, and used, e.g., as a laboratory equipment cleaner, 60 grams (30.0 wt %) of Lattice " NT200 (FMC Corporation, Philadelphia, PA 19103), 3.0 grams (1.5 wt %) of croscarmellose sodium (Ac-Di-Sof sold by FMC Corporation, Philadelphia, PA 19103), 3.0 grams (1.5 wt %) of synthetic diatomaceous silica, and 0.8 gram (0.4 wt %) of magnesium stearate.
  • control formulations were prepared in which no excipient was added; one in which only Lattice NT200 was included; one in which only synthetic diatomaceous silica was in combination with Lattice NT200; and one in which croscarmellose sodium was in combination with Lattice NT200.
  • the amount of Alconox detergent powder was adjusted to make up for the added excipients.
  • the comparative examples are numbered 6a, 6b, 6c, and 6g, respectively.
  • Table 6 provides the composition of all formulations and a summary of hardness and disintegration times for the tablets prepared from them.
  • Examples 6d, 6e, and 6f are all examples of the invention; however, Example 6e is the specific formulation of the invention that is described in this example. All examples were prepared by the identical method, adjusting the amounts of each component appropriately.
  • Example 6 By the method of Example 6, 136.2 grams (68.1 wt %) of Alcono Detergent powder (Alconox, Inc., New York, NY 10003), 60 grams (30.0 wt %) of Lattice TM NT200, 1.5 grams (0.75 wt %) of croscarmellose sodium (Ac-Di-Sof). 1.5 grams (0.75 wt %) of synthetic diatomaceous silica, and 0.8 gram (0.4 wt %) of magnesium stearate were mixed in a twin cone blender. Tablets weighing approximately 3.0 grams were compressed in the same manner as described in Example 6. The same testing procedures were also used. This specific example is identified as 7a, and the results for this example as well as two comparative examples, 7b and 7c, are shown in Table 7.
  • Example 8 By the method of Example 6, 133.2 grams (66.6 wt %) of Alconox
  • Detergent powder 60 grams (30.0 wt %) of Lattice TM NT200, 3.0 grams (1.5 wt %) of croscarmellose sodium (Ac-Di-Sol ), 3.0 grams (1.5 wt %) of natural diatomaceous silica, and 0.8 gram (0.4 wt %) of magnesium stearate were mixed in a twin cone blender. Tablets weighing approximately 3.0 grams were compressed in the same manner as described in Example 6. The same testing procedures were also used. This specific example of the invention is identified as 8a. The results for this example as well as comparative examples 6g, 8b, and 8c are shown in Table 8.
  • Example 9a in Table 9.
  • control formulations were prepared in which no excipient was added; one in which only synthetic diatomaceous silica was added; one in which only zeolite was added.
  • Table 9 provides the composition of all formulations and a summary of hardness and disintegration times for the tablets prepared from them. Examples 9a and 9b are examples of the invention. Example 9c is included in Table 9 for comparison.
  • Example 6 it will be seen that in Examples 6(d), 6(e), and 6(f). where the disintegrants are combined in accordance with this invention, (where 6(e) represents the specific formulation of the invention that is described in Example 6) the disintegration rate is superior to that of any of the control examples; (a), (b). (f), and (g). This is especially evident in Examples 6(e) and (c), where increased amounts of diatomaceous silica are substituted for the super disintegrant. In Example 7 this improvement is also demonstrated, especially in view of one of the disintegration rates in Example 7(a), of the invention, which is about half that of the control examples. In Example 8a, it will be seen that the combination of super disintegrant with natural diatomaceous earth is effective over diatomaceous silica alone.

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Abstract

Composition utile en tant qu'excipient pour augmenter le taux de désintégration de formulations solides d'agents actifs dans des compositions pharmaceutiques, agricoles, industrielles et autres. Ledit excipient est une composition qui comporte un super-désintégrant et un co-désintégrant.
PCT/US1997/012183 1996-07-23 1997-07-15 Composition desintegrante pour solides dispersibles WO1998003064A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU37265/97A AU3726597A (en) 1996-07-23 1997-07-15 Disintegrant composition for dispersible solids
EP97934137A EP0918456A1 (fr) 1996-07-23 1997-07-15 Composition desintegrante pour solides dispersibles

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US79751796A 1996-07-23 1996-07-23
US08/797,517 1996-07-23
US88918597A 1997-07-07 1997-07-07
US08/889,185 1997-07-07

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WO1998003064A1 true WO1998003064A1 (fr) 1998-01-29

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PCT/US1997/012183 WO1998003064A1 (fr) 1996-07-23 1997-07-15 Composition desintegrante pour solides dispersibles

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Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5989589A (en) * 1997-10-24 1999-11-23 Cartilier; Louis Cross-linked cellulose as a tablet excipient
WO1999061037A1 (fr) * 1998-05-22 1999-12-02 Amway Corporation Composition a base de matiere vegetale
WO2000000582A1 (fr) * 1998-06-26 2000-01-06 Henkel Kommanditgesellschaft Auf Aktien Procede de production de detergents et nettoyants sous forme de corps moules
EP1006148A1 (fr) * 1998-11-30 2000-06-07 Kurt H. Prof. Dr. Bauer Produit polysaccharidique co-travaillé
WO2000053716A1 (fr) * 1999-03-11 2000-09-14 Henkel Kommanditgesellschaft Auf Aktien Corps moules de lavage et de nettoyage contenant une association tensioactif/adjuvant de lavage
EP1070740A1 (fr) * 1999-07-19 2001-01-24 Emess AG Produit polysaccharidique co-travaillé avec une carboxyméthylcellulose insoluble
EP1070741A1 (fr) * 1999-07-19 2001-01-24 Emess AG Produit polysaccharidique co-travaillé avec du polyvinylpyrrolidone réticulé
WO2001011000A1 (fr) * 1999-08-10 2001-02-15 Ineos Silicas Limited Compositions de nettoyage
WO2001012767A1 (fr) * 1999-08-12 2001-02-22 The Procter & Gamble Company Composant de desintegration et composition detergente contenant ce composant
US6358910B1 (en) 1997-06-06 2002-03-19 Lever Brothers Company, Divison Of Conopco, Inc. Detergent compositions
US6372707B1 (en) 1997-06-06 2002-04-16 Lever Brothers Company, Division Of Conopco, Inc. Cleaning compositions
WO2003030868A1 (fr) * 2001-10-09 2003-04-17 Bristol-Myers Squibb Company Formes posologiques orales obtenues par fusion-eclair
SG108230A1 (en) * 2000-04-12 2005-01-28 Bristol Myers Squibb Co Flash-melt oral dosage formulation
WO2011148209A3 (fr) * 2010-05-28 2012-05-31 Egis Gyógyszergyár Nyilvánosan Működő Részvénytársaság Nouvelle utilisation de la terre de diatomées dans l'industrie pharmaceutique
NO340570B1 (no) * 2001-10-09 2017-05-15 Otsuka Pharma Co Ltd Flash-smelte farmasøytisk oral doseringsformulering
WO2022258453A1 (fr) * 2021-06-07 2022-12-15 Unilever Ip Holdings B.V. Composition de pastille
WO2024052103A1 (fr) * 2022-09-08 2024-03-14 Unilever Ip Holdings B.V. Composition de lessive

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US4780315A (en) * 1985-11-25 1988-10-25 Eastman Kodak Company Rumen-stable pellets
US5074902A (en) * 1990-07-30 1991-12-24 Connick Jr William J Granular products containing fungi encapsulated in a wheat gluten matrix for biological control of weeds
US5314852A (en) * 1992-11-13 1994-05-24 Fred Klatte Chemically impregnated zeolite and method for chemically impregnating and coating zeolite

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4780315A (en) * 1985-11-25 1988-10-25 Eastman Kodak Company Rumen-stable pellets
US5074902A (en) * 1990-07-30 1991-12-24 Connick Jr William J Granular products containing fungi encapsulated in a wheat gluten matrix for biological control of weeds
US5314852A (en) * 1992-11-13 1994-05-24 Fred Klatte Chemically impregnated zeolite and method for chemically impregnating and coating zeolite

Cited By (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6372707B1 (en) 1997-06-06 2002-04-16 Lever Brothers Company, Division Of Conopco, Inc. Cleaning compositions
US6358910B1 (en) 1997-06-06 2002-03-19 Lever Brothers Company, Divison Of Conopco, Inc. Detergent compositions
US5989589A (en) * 1997-10-24 1999-11-23 Cartilier; Louis Cross-linked cellulose as a tablet excipient
US6232351B1 (en) 1998-05-22 2001-05-15 Amway Corporation Co-processed botanical plant composition
WO1999061037A1 (fr) * 1998-05-22 1999-12-02 Amway Corporation Composition a base de matiere vegetale
WO2000000582A1 (fr) * 1998-06-26 2000-01-06 Henkel Kommanditgesellschaft Auf Aktien Procede de production de detergents et nettoyants sous forme de corps moules
EP1006148A1 (fr) * 1998-11-30 2000-06-07 Kurt H. Prof. Dr. Bauer Produit polysaccharidique co-travaillé
WO2000053716A1 (fr) * 1999-03-11 2000-09-14 Henkel Kommanditgesellschaft Auf Aktien Corps moules de lavage et de nettoyage contenant une association tensioactif/adjuvant de lavage
EP1070740A1 (fr) * 1999-07-19 2001-01-24 Emess AG Produit polysaccharidique co-travaillé avec une carboxyméthylcellulose insoluble
EP1070741A1 (fr) * 1999-07-19 2001-01-24 Emess AG Produit polysaccharidique co-travaillé avec du polyvinylpyrrolidone réticulé
WO2001011000A1 (fr) * 1999-08-10 2001-02-15 Ineos Silicas Limited Compositions de nettoyage
WO2001012767A1 (fr) * 1999-08-12 2001-02-22 The Procter & Gamble Company Composant de desintegration et composition detergente contenant ce composant
US20130296337A1 (en) * 2000-04-12 2013-11-07 Bristol-Myers Squibb Company Flashmelt oral dosage formulation
SG108230A1 (en) * 2000-04-12 2005-01-28 Bristol Myers Squibb Co Flash-melt oral dosage formulation
EP1566174A3 (fr) * 2000-04-12 2007-04-04 Bristol-Myers Squibb Company Forme de dosage orale très fondante
US9358207B2 (en) * 2000-04-12 2016-06-07 Otsuka Pharmaceutical Co., Ltd. Flashmelt oral dosage formulation
US8518421B2 (en) 2000-04-12 2013-08-27 Bristol-Myers Squibb Company Flashmelt oral dosage formulation
WO2003030868A1 (fr) * 2001-10-09 2003-04-17 Bristol-Myers Squibb Company Formes posologiques orales obtenues par fusion-eclair
NO340570B1 (no) * 2001-10-09 2017-05-15 Otsuka Pharma Co Ltd Flash-smelte farmasøytisk oral doseringsformulering
WO2011148209A3 (fr) * 2010-05-28 2012-05-31 Egis Gyógyszergyár Nyilvánosan Működő Részvénytársaság Nouvelle utilisation de la terre de diatomées dans l'industrie pharmaceutique
WO2022258453A1 (fr) * 2021-06-07 2022-12-15 Unilever Ip Holdings B.V. Composition de pastille
WO2024052103A1 (fr) * 2022-09-08 2024-03-14 Unilever Ip Holdings B.V. Composition de lessive

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CA2258917A1 (fr) 1998-01-29
AU3726597A (en) 1998-02-10

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