CN103517945B - Without the polyvinyl alcohol compositions of talcum - Google Patents

Without the polyvinyl alcohol compositions of talcum Download PDF

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Publication number
CN103517945B
CN103517945B CN201280021735.1A CN201280021735A CN103517945B CN 103517945 B CN103517945 B CN 103517945B CN 201280021735 A CN201280021735 A CN 201280021735A CN 103517945 B CN103517945 B CN 103517945B
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China
Prior art keywords
composition
talcum
film
dressing
solid
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CN201280021735.1A
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Chinese (zh)
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CN103517945A (en
Inventor
P.J.谢斯基
M.E.马图西
P.C.加西亚托德
K.M.巴尔温斯基
D.L.霍尔布鲁克
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Dow Global Technologies LLC
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Dow Global Technologies LLC
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Classifications

    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L29/00—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an alcohol, ether, aldehydo, ketonic, acetal or ketal radical; Compositions of hydrolysed polymers of esters of unsaturated alcohols with saturated carboxylic acids; Compositions of derivatives of such polymers
    • C08L29/02—Homopolymers or copolymers of unsaturated alcohols
    • C08L29/04—Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
    • C09D129/00—Coating compositions based on homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an alcohol, ether, aldehydo, ketonic, acetal, or ketal radical; Coating compositions based on hydrolysed polymers of esters of unsaturated alcohols with saturated carboxylic acids; Coating compositions based on derivatives of such polymers
    • C09D129/02—Homopolymers or copolymers of unsaturated alcohols
    • C09D129/04—Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids

Abstract

The invention provides without talcum composition, it is characterized in that non-sticky and have at the most 5.0 × 10-7Gram every Pascal-hour-the average water vapor permeation rate of meter and there is the ability that forms non-adhesive film, described non-adhesive film has at the most 5.0 × 10-7Gram every Pascal-hour-the average water vapor permeation rate of meter. Non-adhesive film is also provided, by the method for described composition coated dosage form and the manufactured goods that comprise described composition.

Description

Without the polyvinyl alcohol compositions of talcum
Technical field
The present invention generally relate to inviscid without talcum composition, non-adhesive film, comprise described compositionManufactured goods and by the method for described composition coated dosage form.
Background technology
The talcose dressing of pharmaceutical dosage form and nutriment formulation is at present for commercial use. Talcum conforms with the phaseHope and give the low viscosity of dressing or inviscid, this makes can pack quickly and carry at production periodMore easily process and gulp down for patient for more clean method (not having tablet dust to produce) and preparationThe formulation of pharynx. For example, reduce the dressing (OPADRYII based on PVOH of business with talcum(Colorcon,Inc.,Harleysville,Pennsylvania;BPSIHoldingsLLC,WilmingtonDelaware, the Jun Shi U.S.)) viscosity.
Some dressings of known drug formulation or nutriment formulation it is believed that and not need talcum, although preferablyIn embodiment, they can use talcum in line with expectations. These dressings of a part (but not all)Polyvinyl alcohol (PVOH) or carboxymethyl cellulose (CMC) (but not the two all uses) are usedAs the reagent that forms film. For example, see WO2009/031039A2 and US2010/0062062A1.WO2009/031039A2 mentions the CMC coating material of the special molecular weight-modification of independent use,Or it is combined with the hydrocolloid of other type, biogum (biogums), cellulose ether etc. RemoveOutside basic modification CMC dressing reagent, coating material can also comprise other other formation aboveThe reagent of film, instead of hydrocolloid, cellulose ether and/or biogum. US2010/0062062A1 is outstandingIt is mentioned drug powder or the particle of selected excipient and PVOH-dressing is pressed into tablet. Therefore,Coated drugs powder or particle are pressed into tablet and need adhering to each other or bonding or and the figuration of its dressingAgent or the two adhesion or bondingly carry out by this way, to form tablet. Therefore, at USIn 2010/0062062A1, PVOH dressing is viscosity undesirably.
The problem that the present invention solves comprises to be provided without talcum composition, it is characterized in that non-sticky and hasLow water vapor permeation rate.
Summary of the invention
The inventor recognizes that talcum makes dressing opaque and brighten, and this is coloured, transparent or two for needsSome formulation application of person's dressing are not conform with expectation. The inventor also recognizes separately and comprisesPVOH or the dressing that comprises separately CMC have one or more shortcomings independently, and described shortcoming comprisesViscosity, opaque, coloured, vapor permeable or their combination. They find independent PVOHDressing is at least viscosity, and independent CMC dressing is at least muddy and has unacceptable water and steamVapour permeability. The inventor has found to be characterized as non-sticky beyond expectationly and had low water vapour oozesThoroughly rate without talcum composition. Some preferred embodiment in, still quite saturating without talcum compositionBright, not muddy or their combination. In some embodiments, unless by independent colorAdditive (as pigment or dyestuff) adds without in talcum composition, otherwise without talcum composition or colourless.
In the first embodiment, the invention provides without talcum composition, it is characterized in that non-sticky,And have at the most 5.0 × 10-7(0.0000005) gram every Pascal-hour-the average water of meter (g/Pa.h.m.) steamsVapor permeance and have the ability of non-adhesive film of formation, described non-adhesive film has at the most 5.0 × 10-7G/Pa.h.m. average water vapor permeation rate.
Preferably, there is further character (a) and (b) by the non-adhesive film of preparing without talcum compositionAt least one: (a) the standardization film transparency of at least 500% every millimeter of thickness (%/mm); (b)13% film mist degree (filmhaze) at the most. In some other embodiments, character (b) is at the most250% every millimeter of thickness (%/mm), preferably 180%/mm thickness at the most, more preferably 120%/mm at the mostThickness, still more preferably 80%/mm thickness at the most, even more preferably 25%/mm thickness at the most, andMore preferably the standardization film mist degree of 13%/mm thickness at the most again. For applying at business solid chemicals dressingNormally used thickness in (as medicine, nutriment and veterinary drug (veterinarian) application), the present inventionNon-adhesive film there is 13% mist degree at the most. In some embodiments, at least wrap without talcum compositionContaining character (a), in some other embodiment, at least comprise character (b), in other other realityExecute in mode, comprise character (a) and (b) the two.
In the second embodiment, the invention provides the method for the solid dosage forms of preparing dressing, described sideMethod comprises makes connecing without the healthy preparation of talcum composition and the solid that comprises active component of dressing-effective doseTouch, described contact is carried out in mode so, so that the healthy preparation of coated solid, thereby obtain comprising non-The coated solid formulation of adhesive film, described non-adhesive film comprises without talcum composition, and this non-adhesive film is with solidThe healthy preparation of body carries out dressing work contact (coatingoperativecontact) and has at the most 5.0 × 10-7Gram every Pascal-hour-the average water vapor permeation rate of meter. Preferably, dressing work contact refers to non-stickyProperty film has fully been coated the surface of solid dosage forms.
In the 3rd embodiment, the invention provides the manufactured goods that comprise without talcum composition. Preferably,Manufactured goods comprise the solid dosage forms of dressing.
In another embodiment, the invention provides the non-adhesive film comprising without talcum composition.
Composition of the present invention for example can be used as the adhesive for the wet granulation of the healthy preparation of solid; WithIn dressing or film, especially pharmaceutical dosage form, veterinary drug formulation and the nutriment agent of preparing coated solid formulationType (being referred to as in this application formulation). For example, composition of the present invention can be used for dressing nutriment sheetAgent, to obtain the tablet of dressing, wherein consumer preferably their nutriment tablet look natural; ?On medicinal tablet or veterinary drug tablet, produce gloss; With the transparent or coloured dressing of preparation. Coloured dressingGive in line with expectations formulation attractive in appearance and shade function that can cutting, it can be for differentiating different dosageIntensity. Composition of the present invention also can be used for other application, and as adhesive, starching is (as fabric and paperStarching), and emulsifying soln, suspend, and thickening application.
Advantageously, the invention provides can form non-adhesive film or dressing without talcum composition, described inNon-adhesive film or dressing have at the most 5.0 × 10-7G/Pa.h.m. average water vapor permeation rate. Excellent at someIn the embodiment of choosing, there is the above-mentioned character of mentioning (a) and (b) at least one without talcum compositionKind, and more preferably have character (a) and (b) the two. Additional advantage can comprise that film is at tablet bagClothing method has reduced viscosity the tablet of dressing is not reunited during carrying out, improved visible film outward appearance(as compared with talcose non-dressing of the present invention, film defect (as breaking) reduces), and shortened bagThe time that garment piece agent is required.
Other embodiment of the present invention is described in the application's remainder (it comprises claim)In.
Detailed description of the invention
Embodiments of the present invention are existing general introduction previously, and by summary by reference to being incorporated to herein. This ShenThe term " active component " that please used refers to that intention provides in the occasion of nutriment, medicine or veterinary drugAny compound or the material of health advantages. Term " dressing " refers to have surperficial clad material or film.Term " dressing-effective dose " refers to be enough to carry out coated consumption by forming film. Term " dressing workContact " refer to non-directly (passing through intermediate materials) or preferably directly carry out the surface bag of physical contactCover material material, preferably contacts in fact whole surface. Term " composition " refer to the qualitative of chemical substance orQuantitative constituent, it comprises homogeneous phase material and heterogeneous materials. Term " contact " is (to connect with somethingTactile form) etc. be instigate together or contact. Term " formulation " refers to and is suitable for activity in the applicationPhysical form or the structure of the administration of composition to human or animal. Term " coated solid formulation " refers to healthThe coated variant (variant) of film of preparation, it has clear and definite shape and volume (with " liquid " phaseInstead). Term " healthy preparation " refer at least one active component and be suitable for nutriment, medicine,Or at least one other composition in veterinary drug occasion or the preparation of component. Term " film " refers to thin being coatedMaterial, generally has the thickness of 1.0 millimeters (mm) at the most. Term " manufactured goods " refers to a class thingThe member of thing, wherein this member is not found in occurring in nature. Term " non-sticky " refers to " not bonding "Result, it uses viscosity method of testing hereinafter described to measure. Term " film transparency " and " markStandardization film transparency " refer to respectively the result of film transparency method of testing hereinafter described or the knot of conversionReally, it can be used for comparison. Term " film mist degree " and " standardization film mist degree " refer to respectively hereinafter describedThe result of film mist degree method of testing or the result of conversion, it can be used for comparison. Term " work contact "Refer to non-directly (passing through intermediate materials) or direct physical contact preferably. Term " without talcum " isRefer to not containing by hydrated magnesium silicate, (it has chemical formula H2Mg3(SiO3)4Or Mg3Si4O10(OH)2) formMineral. Term " water vapor permeation rate " and " WVT permeability " are synonyms, and it refers to belowThe result of described water vapour permeability method of testing.
The processing of conflict: the institute's content of writing in this description and the patent, patent application by reference to introducing,Or Patent Application Publication or its part have any conflict, be as the criterion with the content of being write in this description. KnotStructure has any conflict with compound name, is as the criterion with structure. The unit value of not describing with bracket and bracket insertThe predetermined corresponding unit value of describing has any conflict, is as the criterion with the unit value of not describing with bracket.
Digital scope: the optional preferred lower limit in interval digital any lower limit or this interval canTo be combined with any upper limit in this interval or the optional preferred upper limit in this interval, excellent with interval of definitionSelection condition or embodiment. Unless otherwise noted, to comprise that this interval comprises all for the numeral in each intervalNumeral, rational and irrational number the two (as " 1 to 5 " comprises, for example, 1,1.5,2,2.75,3,3.81,4 and 5).
In some embodiments, partially enclosed phrase " in fact by ... composition " has replaced openingTerm " comprises ". In these embodiments, can comprise other composition, bar without talcum compositionPart is their not negative effects fundamental characteristics of the present invention and novel characteristics. These fundamental characteristics of the present inventionWith novel characteristics be aforesaid non-sticky and average water vapor permeation rate. In some embodiments, basicCharacteristic and novel characteristics also comprise character (a) and (b) at least one, preferably include the two.
Preferably, comprise low viscous polyvinyl alcohol (LV-PVOH) and antistick characteristic without talcum compositionOrganic adjuvant, the wherein weight of LV-PVOH and antistick characteristic organic (TRO) adjuvant in composition/Weight ratio is >=60:40 is to≤95:5. In some embodiments, LV-PVOH/TRO adjuvant wt/wtThan being 61:39 at least, LV-PVOH/TRO adjuvant wt/wt ratio is at least in other embodiments65:35, LV-PVOH/TRO adjuvant wt/wt ratio is 7:3 at least in other embodiments, at otherIn embodiment, LV-PVOH/TRO adjuvant wt/wt ratio is 8:2 at least. In some embodiments,LV-PVOH/TRO adjuvant is 94:6 at the most, and LV-PVOH/TRO adjuvant is in other embodiments91:9 at the most, LV-PVOH/TRO adjuvant is 90:10 at the most in other embodiments, real at otherExecute in mode LV-PVOH/TRO adjuvant and be 8:2 at the most. In some embodiments, LV-PVOH/TROAdjuvant wt/wt ratio is 6:4, and LV-PVOH/TRO adjuvant wt/wt ratio is 7:3 in other embodiments,LV-PVOH/TRO adjuvant wt/wt ratio is 8:2 in other embodiments, in other embodimentsLV-PVOH/TRO adjuvant wt/wt ratio is 9:1, LV-PVOH/TRO adjuvant in other embodimentsWt/wt ratio is 19:1. Term " low viscosity polyvinyl alcohol " and " LV-PVOH " are synonyms, and it isThe repetitive, 2 millis handkerchief-second (mPa.s) that refers to have derived from ethylene alcohol to the dynamic viscosity of 10mPa.s,With oligomeric materials or the polymeric material of 80 mole percents (mol%) to the saponification degree of 95mol%,Described dynamic viscosity 20 DEG C adopt 4 weight per volume percentages (wt/vol%, in gram LV-PVOHWeight is often in the deionized water volume of milliliter) its aqueous solution measure. Preferably, dynamic viscosity3mPa.s to 9mPa.s, and more preferably 3.5mPa.s to 8mPa.s(as 4mPa.s to 7MPa.s), all adopt its aqueous solution of 4wt/vol% to measure at 20 DEG C. Preferably, saponification degree84mol% to 92mol%, and more preferably 85mol% to 90mol%(as 86.5mol% extremely89.0mol%). Saponification degree is relevant with LV-PVOH, LV-PVOH by saponification (as used NaOH waterSeparate) the acetate official energy of aforementioned mol% in inferior terminal groups (penultimate) polyvinyl acetateDegree is to obtain LV-PVOH and acetic acid (in pH and time) and to remove acetic acid (as evaporation) and carry outPreparation.
The term " the organic adjuvant of antistick characteristic " that the application uses or " TRO adjuvant " refer to except PVOHOutside material, wherein said material comprises carbon atom, hydrogen atom and oxygen atom and optional nitrogen-atoms,The function of wherein said material is to reduce the viscosity of LV-PVOH, and preferably, has also improvedAt least one character of LV-PVOH, described character is that light transmission is (as transparency, mist degree or preferably twoPerson) or water vapor permeability, can not have to make the present composition there is independent PVOHFunctional. Preferably, TRO adjuvant is the organic polymer that forms transparent non-adhesive film. OneIn a little embodiments, TRO adjuvant is carboxymethyl cellulose (CMC), polyethylene glycol, hydroxypropyl methylCellulose (HPMC), maltodextrin, methylcellulose or polyvinylpyrrolidone (PVP),Or their combination. More preferably, TRO adjuvant is CMC.
In some embodiments, also comprise following material without talcum composition or in fact by following materialComposition: at least one other composition of non-counteracting amount, i.e. second organic adjuvant. Term " non-counteracting amount "Referring to not can the aforesaid non-sticky of negative effect and the amount of average water vapor permeation rate. Preferably, described amountCan negative effect character (a) and at least one (preferably the two) of character (b) yet. Preferably,Described at least one other composition (second organic adjuvant) is plasticizer, removable dispersant, tableFace activator (surfactant) or their combination of at least two kinds. In some embodiments,Plasticizer and TRO adjuvant are identical compositions, and in other embodiments, they are different compositions.In some embodiments, plasticizer and removable dispersant are identical compositions, in other enforcement sideIn formula, they are different compositions. In some embodiments, plasticizer and surfactant are identicalComposition, in other embodiments, they are different compositions. Term " removable dispersant "Refer to volatile materials, its for preparation in volatile materials, contain wide distribution LV-PVOH andSuspension, solution or their combination of TRO adjuvant is that effectively described volatile materials is 101KPa (kPa) pressure have lower than approximately 130 degrees Celsius (DEG C) boiling point (b.p.). Preferably, waveThe b.p. of volatile material is approximately 0 DEG C to approximately 115 DEG C, more preferably from about 30 DEG C to 110 DEG C and still morePreferably approximately 34 DEG C to approximately 105 DEG C, all at 101kPa. Preferably, removable dispersant beThe liquid of 20 DEG C and 101kPa. In the time comprising removable dispersant further without talcum composition,Preferably removable dispersant is the 50wt% to 99wt% without the gross weight of talcum composition, and logicalBe often the 50wt% to 98wt% without the gross weight of talcum composition, described gross weight comprises removableThe weight of dispersant. Preferably, removable dispersant be effectively for dissolve without talcum composition withObtain the solvent of its solution, wherein said solution is can be used for being applied in one in the healthy preparation of solidIndividual temperature. The example of preferred removable dispersant is acetic acid, acetone, ethanol, ethyl acetate, firstAlcohol and preferred water. Term " plasticizer " refers to effective increase consolidating without the mobility of talcum compositionBody or liquid substance. In the time comprising plasticizer further without talcum composition, preferably plasticizer is nothingThe 0.01wt% of the gross weight (not comprising the weight of any removable dispersant) of talcum composition extremely20wt%. Preferably, plasticizer is nonvolatilely (to have and be greater than approximately 150 at 101kPa pressureDegree Celsius (DEG C) b.p.), from without talcum composition, remove any remove dispersant after,Plasticizer is retained in fully without in talcum composition. In the time using, in some embodiments, plasticisingAgent with without talcum composition form blend, wherein do not have covalently bound, in other embodiments at leastSome plasticizer react to form covalent bond (as passed through carboxylic with at least some LV-PVOH or TRO adjuvantThe esterification of acid). The example of preferred plasticiser is glycerine, polyethylene glycol (PEG) and lecithin.The example of suitable PEG be PEG-400, PEG-3350 and business derive from Sigma-AldrichCompany, St.Louis, Missouri, USA or TheDowChemicalCompany, Midland,Michigan, other PEG of USA. For example, Dow provides CARBOWAXTMThe PEG of trade mark,Its number-average molecular weight scope is 200g/mol to 8000g/mol. These PEG(are flat in g/mol'sAll Mn scopes) comprise PEG-4 (190-210), PEG-6 (285-315), PEG-8 (380-420),PEG-6/PEG-32 blend, PEG-12 (570-630), PEG-20 (950-1050), PEG-32(1305-1595)、PEG-75(3015-3685)、PEG-90(3600-4400)、PEG-100(4400-4800) and PEG-180 (7000-9000), wherein these PEG are according to thePersonalCareProductsCouncil (predecessor is Cosmetics, ToiletriesandFragrancesAssociation),Washington, D.C., PEG nomenclature, use InternationalNomenclature that USA sets upCosmeticIngredient name pact is named. In some embodiments, without talcum compositionComprise further plasticizer, TRO adjuvant is the composition that is different from plasticizer, and plasticizer is poly-second twoAlcohol, preferred PEG-400. Term " surfactant " and " surfactant " are synonyms, and it isFinger can reduce the capillary material of water. When comprising further surfactant without talcum compositionTime, preferably, surfactant is (not comprise any removable point without the gross weight of talcum compositionThe weight of powder) 0.001wt% to 1wt%. Surfactant is emulsification by the example of Function ClassificationAgent, wetting agent, blowing agent, dispersant and antifoaming agent. Surfactant by the example of textural classification be fromSubtype surfactant and nonionic surface active agent. The example of ionic surfactant is anionType surfactant (as lauryl sodium sulfate), cationic surface active agent are (as cetyl threeMethyl ammonium bromide) and amphoteric surfactant (as amino acid). The example of nonionic surface active agentThat fatty alcohol, polyoxypropylene glycol and polysorbate are (as polyoxymethylene (20) sorbierite list oilEster (be polysorbate80, be called to business Tween80)).
In some embodiments, comprise further glycerine without talcum composition or PEG waves as non-The plasticizer of the property sent out. In some embodiments, without talcum composition comprise further glycerine orPEG (as non-volatile plasticisers) and polysorbate ester surfactant. In some embodiments,Comprise further water as removable dispersant without talcum composition, in other embodiments, nothingTalcum composition is not in fact containing removable dispersant. In some embodiments, without talcum compositionComprise LV-PVOH, as the CMC of TRO adjuvant with as the PEG of non-volatile plasticisers.In some embodiments, without talcum composition comprise LV-PVOH, as the CMC of TRO adjuvant,As PEG and the polysorbate ester surfactant of non-volatile plasticisers. In some embodiments,The aqueous solution that comprises LV-PVOH, CMC and PEG without talcum composition, in some other enforcement sideThe aqueous solution that comprises LV-PVOH, CMC, PEG and polysorbate without talcum composition in formula.In some embodiments, without talcum composition, not containing lecithin, it is further in other embodimentsGround comprises the lecithin of low concentration (as < 1 percetage by weight (wt%)) at the most. In some embodiments,Without talcum composition, as described in any of aforementioned embodiments in this section, difference is that CMC isUnique TRO adjuvant, does not contain HPMC, methylcellulose, maltodextrin without talcum compositionAnd PVP. In some embodiments, without talcum composition as any of aforementioned embodiments in this sectionDescribed in (but not being front a kind of embodiment immediately), difference be CMC completely by HPMC,Methylcellulose is (as METHOCELTM), maltodextrin, PVP or their combination replace.
Preferably, healthy preparation is nutriment formulation, pharmaceutical dosage form or veterinary drug formulation. Preferably, agentType is unit dosage forms. Healthy preparation can be any physical form. The example of suitable physical form isContain solid and the physical form containing liquid. The example of the suitable healthy preparation of solid is that pearl is (as unique pearl(nonpareilbead)), powder, particle, tablet (as prepared by pressed powder), capsule (asGelatine capsule or its component), capsule and pill sheet (gelcaptablet), lozenge, patch and lozenge. Solid is strongAt least some compositions of health preparation are solid constituents. The present invention expects that the healthy preparation of solid is in some enforcement sidesAt least one liquid component that comprises small amount further in formula, it only comprises in other embodimentsSolid constituent. The feature of each solid constituent of the healthy preparation of solid can be unbodied, partially crystallizable,Or crystallization. Composition of the present invention can be used as the composition in the healthy preparation of solid or is preferably consolidatingDressing or formation film on the healthy preparation of body. The example of the suitable healthy preparation containing liquid be emulsifiable paste, elixir,Emulsion, gel, washing lotion, ointment, solution (as in water) and syrup. Composition of the present invention canBe used as at the composition containing in the healthy preparation of liquid.
Preferably, active component is the active component of nutriment, medicine or veterinary drug. The active one-tenth of nutrimentDivide meals, nutrition or preventative health advantages are provided. Active component can be solid or liquid. ?In some embodiments, the healthy preparation of solid comprises liquid actives, and it is distributed in widely solid and composesOn shape agent (as solid carrier) or among, in some other embodiment, solid active agent is wideBe distributed among liquid excipient (as liquid-carrier) generally, in other other embodiment,Solid active agent be distributed in widely in solid excipient in case with its formation blend. Nutriment activityThe example of composition be dietary supplements (as antioxidant (as resveratrol), flavone compound (asFrom citrus fruit, tea, wine or cocoa bean), draft, mineral, naturally occurring amino acid,And vitamin) and condensed food (as glycinin reinforced oat bar). Medicine or veterinary drug active componentProvide the health advantages for the treatment of disease (to reach sending out of at least one symptom as increased in prophylactic treatmentTime of doing, in palliative therapy, alleviate the seriousness of at least one symptom or be suppressed at and need this classIn the mankind for the treatment of or animal patient, the pathology effects of the disease adjusting of disease or deficiency disorder treatment sends outExhibition. ) example of active constituents of medicine or veterinary drug active component is anodyne (as Carprofen), vasotoniaElement converting Enzyme (ACE) inhibitor (as quinapril, example hydrochloric acid quinapril), antibiotic (as AhMiramycin), anticonvulsive drug (as Gabapentin), antidepressant (for example, Sertraline, example hydrochloric acid house is bentWoods), anti-fibromyalgia (anti-fibromyalgic) (for example, lyrica), antihypertensive (exampleAs Amlodipine, as Amlodipine Besylate Tablet) and (for example, atropic cuts down him to reduce the medicine of cholesterolSpit of fland, as Atorvastatin calcium).
In some embodiments, healthy preparation comprise further with active component form mixture extremelyFew a kind of acceptable excipient. Term " mixture " refers to the product being blended together. Term " canThe excipient of accepting " refer to be applicable in healthy preparation and any compound or the thing of non-active ingredientMatter. Preferably, acceptable excipient is the acceptable excipient of nutriment, medicine or veterinary drug. BattalionThe example of supporting the acceptable excipient of product, medicine or veterinary drug is carrier; Diluent; Stabilizing agent; NutritionThe adjuvant of product, medicine and veterinary drug; With the characteristic composition of formulation, if the softgel shell for capsule is (as gelatin glueSoftgel shell) and for pellicle and the lining (backings) of transdermal patch.
In some embodiments, comprise further removable dispersant without talcum composition, preparationThe method of coated solid formulation has adopted removable dispersant further. Be used for obtaining coated solid agentThe dressing of the healthy preparation of the solid of type preferably carries out as follows: at (solid) healthy preparationExposed surface application surface dressing-effective dose can remove dispersant (for example, solvent, as ethanol orWater) in the suspension without talcum composition or preferred solution, thereby so use without talcum compositionThe exposed surface of coated (solid) healthy preparation equably; With from coated (solid) healthy preparationRemove removable dispersant, to obtain the solid dosage forms of dressing. Term " surface coatings-effective dose "Refer to the consumption that is enough to coated exposed surface. The example of using is to spray, flood and rolling (tumbling).The example of removing is to evaporate, blot and wipe (wiping). Without suspension or the solution of talcum compositionPreferably preparation by the following method: without the dispersant removed of talcum composition and appropriate amount (for example, makeSolvent is as ethanol or water) contact, to obtain its suspension or solution. The example of contact is to stir(agitating), jolting, injection, stirring (stirring) and rolling.
Preferably, manufactured goods comprise healthy preparation, described healthy preparation comprise active component and with its workContact without talcum composition.
Illustrative embodiment of the present invention is below provided, and wherein embodiment (comprising some preparation) usesSome method and material. Described method, material and preparation are described in next part.
LV-PVOH: refer to from NipponGohsei Osaka, the GohsenolEG-05P of Japan.GohsenolEG-05P has saponification degree and the 4.8mPa.s to 5.8 of 86.5mol% to 89.0mol%The dynamic viscosity (it is measured at 20 DEG C of aqueous solution with 4wt/vol%) of mPa.s.
CMC: refer to sodium carboxymethylcellulose CRT-30PA, DS=0.9, lot7M650, it derives from The DowChemicalCompany,Midland,Michigan,USA。
PEG-400 and PEG-3350: refer to respectively CARBOWAXSENTRY PEG400 NF,WL0101AAKC and CARBOWAXSENTRY PEG3350, derive from TheDowChemicalCompany。
Polysorbate80 (Tween80): refer to enzyme grade 943317, it derives from FisherScientific.
Tablet: (the red capsule label of 100g, 493g white ovals tablet, 6.5g are white to refer to placebo tabletLook disk), it derives from TheDowChemicalCompany.
Dynamic viscosity method of testing: use Brookfield-II, D06719 is with suitable number of spindles 2,3,5Or 7 and corresponding 10 rpms (rpm), 20rpm, 50rpm and 100rpm test solutionViscosity.
Film preparation: complete all films in stationary temperature (22 DEG C) and relative humidity (50%RH) environmentPreparation and storage. By slow near the curtain coating in 1mm gap (traction (draw) downwards) bar edgePour the solution of 20wt% into, and stably draw subsequently solution to reduce bubble and defect as far as possible, completeHand traction wet film (1mm) on glass plate. Film on drying plate two days, takes off them in slave plate,With one day annealed film with other. To the film test membrane performance after annealing. Preferably, taking off 4 of filmIn it, complete whole films and test to minimize the difference between any sample and sample. When test membrane notTime, under steady temperature and relative humidity, between the scraps of paper, preserve film.
The method of testing of film transparency: use from GardnerLaboratoryInc., Bethesda,Maryland, the PacificScientificPG-5500 of USA and from ZebedeeCorporation,Moore, SouthCarolina, the film transparency of the ZebedeeCL-100 test membrane of USA, it is by openingHole (openport), black standard sample and to be respectively 100%, 0% and 87 (+/-1) % transparentThe membrane standard sample advanced in years of degree is proofreaied and correct. Four diverse locations on each film are read the test of transparencyResult. The mean value of four test results of record.
Film mist degree method of testing: adopt from BYKGardner, Columbia, Maryland, USA,The Haze-gardPlus of CatalogNumber4725 tests the mist degree of prepared film. Report with percentageMist degree reading and transmitance reading the two. The mean value of four readings of record.
By percentage film mist degree and transparency value divided by the thickness in millimeter, thereby obtain percentage markThe standardized film transparency of the film mist degree of standardization and percentage.
Viscosity method of testing: tablet is carried out to dressing according to appropriate embodiment hereinafter described. Coating tabletThe viscosity of agent can be to reunite each other and bonding or do not reunite each other or bonding the qualitative of coated tablet looksFeel and observe. Preferably, viscosity is quantitative percetage by weight, and it equals with prepared coated tabletThe percentage of gross weight (weight of the weight of the coated tablet separating and the part of any reunion) recentlyThe weight of the reunion part (if any) of the coated tablet representing. If reunited, part is < 10Wt%, preferably < 5wt% and more preferably≤1wt% and still more preferably 0wt%( do not reunite),Think that be inviscid for object of the present invention without the dressing of talcum composition and coated tablet. To sampleProduct are taken pictures with the carrying out of comparative experiments.
Water vapour permeability method of testing: use " cheers " method test water vapour permeability. The chlorination of weighingCalcium (2.0g) adds in the wide-mouth bottle of 4 ounces (120ml), makes it in 50% relative humidity (73 DEG C)And with closed ring cover (having therein the hole of 2.5cm diameter), last 1 hour. Then, existA small amount of vacuum grease is placed at bottleneck edge around. Use metal stamping that film is cut into approximately 1.3 inchesThe disk of (3.3 centimetres (cm)) diameter. Membrane sample disk is placed in to wide-mouth bottle top, and will hasThe lid in the hole of 1 inch of (2.5cm) diameter is placed in the top of film disk. Cover tightly lid to form sealing,And guarantee not make film disk to break. Wide-mouth bottle is put into Environ-Cab controller (Lab-Line is housedInstrument, Inc.) temperature-humidity chamber in, be arranged on 75% relative humidity and 25 DEG C. NoteThe gross weight of record wide-mouth bottle, lid, film and calcium chloride, redeterminates gross weight for every 24 hours, continues5 days. Use the weightening finish (m) of gross weight to obtain mass transfer rate to the linear regression of time (t).Area by mass transfer rate divided by exposed film, provides with a gram every square centimeter hour (g/cm2Hr) countWater vapour sees through (WVT) rate,
WVT = m t A ,
Wherein mtBe quality (gram (g/hr) per hour) over time, A is with square centimeter (cm2）The membrane area of the exposure of meter. Calculate membranous permeation rate according to following formula:
Wherein l is thickness, and S is at 25 DEG C of water saturation vapour pressures, RH20.75(75% relative humidity)And RH10. S (RH2-RH1) be to water by the driving force of the mass transfer of film.
Compared with the following non-film without talcum composition of the present invention (a)-(d), of the present invention without slidingThe film of stone composition can be favourable:
(a) film of 100%CMC, this film has standardization film mist degree, the 472%/mm of 14%/mmStandardization film transparency and 12 × 10-7The average WVT permeability of g/Pa.h.m;
(b) film of 100%GohsenolEG-05P, this film is that viscosity is (when according to hereinafter describedTablet coating step is its reunion part that is 13wt% during to tablet coating);
(c) film of 100%GohsenolEG-40P (has the saponification of 86.5mol% to 89.0mol%The dynamic viscosity of degree and 40mPa.s to 46mPa.s (adopts the 4wt/vol% aqueous solution to carry out at 20 DEG CMeasure) high viscosity PVOH), this film is viscosity, it has remarkable increase compared with film (b)The standardization film transparency of standardization film mist degree and decline; With
(d) film of 50:50GohsenolEG-05P/CMC, this film has 7 × 10-7G/Pa.h.m'sAverage water permeability.
Some embodiments of the present invention have more specifically been described in the following example.
Embodiment 1-6:LV-PVOH and CMC without talcum composition. By mixing, at deionization(DI) dissolve whole according to the following material of following table 1 in water (as 100g): 8g to 25g(asGohsenolEG-05P (LV-PVOH) 10g) and CMC and optional plasticizer, thus reality obtainedExecute example 1 to 6 separately as solution (solid of 4wt% to 15wt%) without talcum composition. From portionEvaporation water in point solution, to obtain separately dry without talcum composition of embodiment 1 to 6, it hasGohsenolEG-05PLV-PVOH, CMC as shown in table 1 and optional plasticizer.
Table 1: embodiment 1-6
* wt% is the gross weight based on LV-PVOH, CMC and any plasticizer.
Embodiment A-F: the tablet of dressing. In experiment separately, pack tablet into VectorHi-CoaterType LDCS, its delivery temperature set-point is 40 DEG C. By any solution of embodiment 1-6 with 2.0 toThe injection rate of 2.7 grams per minutes (g/min) is injected on tablet, and the lasting time of calculating, to reachTo 1% to 3% theoretical film weightening finish, thus embodiment A obtained respectively to F coated tablet separately.Aspect following, film and coated tablet are evaluated: viscosity, with gram every Pascal-hour-meter x10-7The average water permeability of meter; With the Film thickness standard film transparency of every millimeter of film thickness gauge of percentage transparency;In the film mist degree of percentage; With the film thickness standardization film mist with every millimeter of film thickness gauge of percent hazeDegree.
Table 2: embodiment A-F
As shown in the Examples, can in solid dosage forms, form non-adhesive film or dressing without talcum composition,This film or dressing have favourable combination or characteristic beyond expectationly, and it comprises at the most 5.0 × 10-7The average water vapor permeation rate of g/Pa.h.m; > the standardization film transparency of 500%/mm; ≤ 13% filmMist degree; In some embodiments, the standardization film mist degree of also comprise < 13%/mm. The tablet of dressingThere is the dressing of the embodiment that comprises non-adhesive film of the present invention, its have the medicine of being applicable to, nutriment andThe thickness of veterinary drug coated tablet application.

Claims (11)

1. without talcum composition, it is characterized in that non-sticky and have at the most 5.0 × 10-7Gram every Pascal-hour-the average water vapor permeation rate of meter and there is the ability that forms non-adhesive film, described non-adhesive filmHave at the most 5.0 × 10-7Gram every Pascal-hour-the average water vapor permeation rate of meter;
Described composition comprises low viscosity polyvinyl alcohol and the organic adjuvant of antistick characteristic, and the poly-second of described low viscosityW/w ratio in described composition is enol with the organic adjuvant of described antistick characteristic >=60:40 to≤95:5；
The organic adjuvant of wherein said antistick characteristic is carboxymethyl cellulose, hydroxypropyl methylcellulose or methyl fibreDimension element;
Wherein said low viscosity polyvinyl alcohol refer to there is derived from ethylene alcohol repetitive, 2mPa.s extremelyThe oligomeric materials of the dynamic viscosity of 10mPa.s and the saponification degree of 80mol% to 95mol% or polymerizationThing material, described dynamic viscosity adopts its aqueous solution of 4 weight per volume percentages to measure at 20 DEG C,Described weight per volume percentage be in gram low viscosity polyvinyl alcohol weight often in the deionization of milliliterWater volume.
Claim 1 without talcum composition, it is further characterized in that at least have at leastThe standardization film transparency of 500% every millimeter of thickness.
Claim 1 without talcum composition, it is further characterized in that to have at the most 13%Film mist degree.
Claim 1 without talcum composition, it is in fact by low viscosity polyvinyl alcohol and antistick characteristicOrganic adjuvant composition.
Claim 1 without talcum composition, the organic adjuvant of wherein said antistick characteristic is carboxymethyl fibreDimension element.
Claim 1 without talcum composition, its in fact also comprise non-counteracting amount at least oneTwo organic adjuvants, described second organic adjuvant is plasticizer, surfactant or removable dispersant.
Claim 6 without talcum composition, wherein said second organic adjuvant be polyethylene glycol,Polysorbate, water; Or the combination of polyethylene glycol, polysorbate and optional water.
8. prepare the method for the solid dosage forms of dressing, described method comprises wants the right of dressing-effective doseAsk contacting without the healthy preparation of talcum composition and the solid that comprises active component of one of 1-7, described contactCarry out in mode so, so that the healthy preparation of solid described in dressing, thereby obtain comprising non-adhesive filmThe solid dosage forms of dressing, described non-adhesive film comprises without talcum composition, and it and the healthy preparation of solid existDressing work contact.
9. manufactured goods, its any one that comprises claim 1-7 without talcum composition.
10. the manufactured goods of claim 9, the solid dosage forms that it comprises dressing, the solid formulation of described dressingType comprises and contains the described non-adhesive film without talcum composition, and the healthy preparation of described non-adhesive film and solid is depositedIn dressing work contact, and described non-adhesive film has at the most 5.0 × 10-7Gram every Pascal-hour-meterAverage water vapor permeation rate.
The non-adhesive film without talcum composition of 11. any one that comprise claim 1-7.
CN201280021735.1A 2011-05-04 2012-04-25 Without the polyvinyl alcohol compositions of talcum Expired - Fee Related CN103517945B (en)

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US20100062062A1 (en) 2008-09-11 2010-03-11 Aethos Pharmaceuticals, Inc. Stabilized Coating for Pharmaceutical Formulations
US8752328B2 (en) * 2009-04-23 2014-06-17 State Of Oregon Acting By And Through The State Board Of Higher Education On Behalf Of Oregon State University Flexible films and methods of making and using flexible films
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