CN103517945A - Talc-free polyvinyl alcohol composition - Google Patents
Talc-free polyvinyl alcohol composition Download PDFInfo
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- CN103517945A CN103517945A CN201280021735.1A CN201280021735A CN103517945A CN 103517945 A CN103517945 A CN 103517945A CN 201280021735 A CN201280021735 A CN 201280021735A CN 103517945 A CN103517945 A CN 103517945A
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- 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
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- 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
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Abstract
The present invention provides a talc-free composition characterizable as non-tacky and having an average water vapor permeability of at most 5.0*10<-7> grams per Pascal-hour-meter and having a capability of forming a non-tacky film having an average water vapor permeability of at most 5.0*10<-7> grams per Pascal-hour-meter. Also provided are the non-tacky film, a method of coating a dosage form with the composition, and a manufactured article comprising the composition.
Description
Technical field
The present invention generally relates to inviscid without talcum composition, non-adhesive film, the finished product that comprise described composition with by the method for described composition coated dosage form.
Background technology
The talcose dressing of pharmaceutical dosage form and nutritious prod formulation is at present for commercial use.Talcum is given the low viscosity of dressing or inviscid in line with expectations, and this makes can pack quickly and provide more clean method (not having tablet dust to produce) and prepare the formulation of more easily processing and swallowing for patient at production period.For example, with talcum, reduce the dressing based on PVOH (OPADRY II (Colorcon, Inc., Harleysville, the Pennsylvania of business; BPSI Holdings LLC, the Wilmington Delaware ，Jun Shi U.S.)) viscosity.
Some dressings of known drug formulation or nutritious prod formulation it is believed that and not need talcum, although they can use talcum in line with expectations in a preferred embodiment.These dressings of a part (but not all) have been used polyvinyl alcohol (PVOH) or carboxymethyl cellulose (CMC) (but not the two all uses) as 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 hydro-colloid of other type, xanthan gum (biogums), ether of cellulose etc.Except above basic modification CMC dressing reagent, coating material can also comprise the reagent of other other formation film, rather than hydro-colloid, ether of cellulose and/or xanthan gum.US2010/0062062A1 especially mentions drug powder or the particle of selected vehicle and PVOH-dressing is pressed into tablet.Therefore, coated drugs powder or particle being pressed into tablet needs its dressing adhering to each other or bonding or with vehicle or the two adhesion or bondingly carry out by this way, to form tablet.Therefore,, in US2010/0062062A1, 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 has low water vapor permeation rate.
Summary of the invention
The inventor recognizes that talcum makes dressing opaque and brighten, and for needs, coloured, transparent or the two some formulations application of dressing are not conform with expectation for this.The inventor also recognizes that the dressing that comprises separately PVOH or comprise separately CMC has one or more shortcomings independently, and described shortcoming comprises viscosity, opaque, coloured, vapor permeable or their combination.They find that independent PVOH dressing is at least viscosity, and independent CMC dressing is at least muddy and has unacceptable vapor permeable fabric laminate.The inventor found to be characterized as non-sticky beyond expectationly and have low water vapor permeation rate without talcum composition.Some preferred embodiment in, without still quite transparent, not muddy or their combination of talcum composition.In some embodiments, unless independent color additives (as pigment or dyestuff) is added 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 vapor permeation rate of meter (g/Pa.h.m.) and there is the ability that forms non-adhesive film, described non-adhesive film has at the most 5.0 * 10
-7g/Pa.h.m. average water vapor permeation rate.
Preferably, by the non-adhesive film of preparing without talcum composition, there is further character (a) and (b) at least one: (a) the stdn film transparency of at least 500% every millimeter of thickness (%/mm); (b) 13% film mist degree (film haze) at the most.In some other embodiments, character (b) is 250% every millimeter of thickness (%/mm) at the most, preferred 180%/mm thickness at the most, more preferably 120%/mm thickness at the most, still more preferably 80%/mm thickness at the most, even more preferably 25%/mm thickness at the most, and the more preferably stdn film mist degree of 13%/mm thickness at the most again.For normally used thickness in business solid chemicals dressing application (as medicine, nutritious prod and veterinary drug (veterinarian) application), non-adhesive film of the present invention has 13% mist degree at the most.In some embodiments, without talcum composition, at least comprise character (a), in some other embodiment, at least comprise character (b), in other other embodiment, comprise character (a) and (b) the two.
In the second embodiment, the invention provides the method for the solid dosage of preparing dressing, described method comprises makes contacting without the healthy preparation of talcum composition and the solid that comprises activeconstituents of dressing-significant quantity, described contact is carried out in mode so, so that the healthy preparation of coated solid, thereby obtain the coated solid formulation that comprises non-adhesive film, described non-adhesive film comprises without talcum composition, and the healthy preparation of this non-adhesive film and solid carries out dressing work and contacts (coating operative contact) and have at the most 5.0 * 10
-7gram every pascal-hour-the average water vapor permeation rate of meter.Preferably, dressing work contact refers to that non-adhesive film has fully been coated the surface of solid dosage.
In the 3rd embodiment, the invention provides the finished product that comprise without talcum composition.Preferably, finished product comprise the solid dosage 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 tackiness agent for the wet granulation of the healthy preparation of solid; Dressing or film, especially pharmaceutical dosage form, veterinary drug formulation and nutritious prod formulation (being referred to as in this application formulation) for the preparation of coated solid formulation.For example, composition of the present invention can be used for dressing nutritious prod tablet, to obtain the tablet of dressing, wherein human consumer preferably their nutritious prod tablet look natural; On medicinal tablet or veterinary drug tablet, produce gloss; With the transparent or coloured dressing of preparation.Coloured dressing gives formulation attractive in appearance and shade function that can cutting in line with expectations, and it can be for differentiating different dose intensities.Composition of the present invention also can be used for other application, and as tackiness agent, starching (as fabric and paper starching), and emulsifying soln, suspend, and thickening application.
Advantageously, the invention provides can form non-adhesive film or dressing without talcum composition, described non-adhesive film or dressing have at the most 5.0 * 10
-7g/Pa.h.m. average water vapor permeation rate.Some preferred embodiment in, without talcum composition, there is the above-mentioned character of mentioning (a) and (b) at least one, and more preferably have character (a) and (b) the two.Additional advantage can comprise that film has reduced viscosity the tablet of dressing is not reunited during tablet coating method is carried out, improved visible film outward appearance (as compared with talcose non-dressing of the present invention, film defect (as breaking) reduces), and shortened the required time of coated tablet.
Other embodiment of the present invention is described in the application's remainder (it comprises claim).
Embodiment
Embodiments of the present invention are existing general introduction previously, and by summary by reference to being incorporated to herein.The term that the application uses " activeconstituents " refers to that intention provides any compound or the material of health advantages in the occasion of nutritious prod, medicine or veterinary drug.Term " dressing " refers to have surperficial coating material or film.Term " dressing-significant quantity " refers to be enough to carry out coated consumption by forming film.Term " dressing work contact " refers to non-directly (passing through intermediate materials) or preferably directly carries out the surperficial coating material of physical contact, preferably contacts in fact whole surface.Term " composition " refers to the qualitative or quantitative constituent of chemical substance, and it comprises homogeneous phase material and heterogeneous materials.Term " contact " (with the form with something contact) etc. be instigate together with or contact.Term " formulation " refers to and is suitable in the application activeconstituents to the physical form of human or animal's administration or structure.Term " coated solid formulation " refers to the variant (variant) that the film of healthy preparation is coated, and it has clear and definite shape and volume (contrary with " liquid ").Term " healthy preparation " refers at least one activeconstituents and is suitable at least one other composition in nutritious prod, medicine or veterinary drug occasion or the preparation of component.Term " film " refers to thin coating material, generally has the thickness of 1.0 millimeters (mm) at the most.Term " finished product " refers to the member of a class things, and wherein this member is not found in occurring in nature.Term " non-sticky " refers to the result of " not bonding ", and it uses viscosity testing method hereinafter described to measure.Term " film transparency " and " stdn film transparency " refer to respectively the result of film transparency testing method hereinafter described or the result of conversion, and it can be used for comparison.Term " film mist degree " and " stdn film mist degree " refer to respectively the result of film mist degree testing method hereinafter described or the result of conversion, and it can be used for comparison.Term " work contact " refers to non-directly (passing through intermediate materials) or direct physical contact preferably.Term " without talcum " refers to not containing by hydrated magnesium silicate, (it has chemical formula H
2mg
3(SiO
3)
4or Mg
3si
4o
10(OH)
2) mineral that form.Term " water vapor permeation rate " and " WVT rate of permeation " are synonyms, and it refers to the result of water vapour permeability testing method hereinafter described.
Conflict processing: in this specification sheets institute the content of writing with by reference to introducing patent, patent application or Patent Application Publication or its part have any conflict, with the content of being write in this specification sheets, be as the criterion.Structure has any conflict with compound name, with structure, is as the criterion.The unit value of not describing with bracket inserts with bracket the predetermined corresponding unit value of describing any conflict, with the unit value of not describing with bracket, is as the criterion.
Digital scope: the optional preferred lower limit in interval digital any lower limit or this interval can be combined with any upper limit in this interval or the optional preferred upper limit in this interval, with preferable case or the embodiment of interval of definition.Unless otherwise noted, the numeral in each interval comprises all numerals that this interval comprises, rational number 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 ... form " replaced open term " to comprise ".In these embodiments, without talcum composition, can comprise other composition, condition is their not negative impacts fundamental characteristics of the present invention and novel characteristics.These fundamental characteristics of the present invention and novel characteristics are aforesaid non-sticky and average water vapor permeation rate.In some embodiments, fundamental characteristics and novel characteristics also comprise character (a) and (b) at least one, preferably include the two.
Preferably, without talcum composition, comprise low viscous polyvinyl alcohol (LV-PVOH) and the organic adjuvant of non-stick property, wherein the w/w ratio of LV-PVOH and non-stick property organic (TRO) adjuvant in composition be >=60:40 is to≤95:5.In some embodiments, LV-PVOH/TRO adjuvant wt/wt ratio is 61:39 at least, LV-PVOH/TRO adjuvant wt/wt ratio is 65:35 at least in other embodiments, LV-PVOH/TRO adjuvant wt/wt ratio is 7:3 at least in other embodiments, and LV-PVOH/TRO adjuvant wt/wt ratio is 8:2 at least in other embodiments.In some embodiments, LV-PVOH/TRO adjuvant is 94:6 at the most, LV-PVOH/TRO adjuvant is 91:9 at the most in other embodiments, and LV-PVOH/TRO adjuvant is 90:10 at the most in other embodiments, and LV-PVOH/TRO adjuvant is 8:2 at the most in other embodiments.In some embodiments, LV-PVOH/TRO adjuvant wt/wt ratio is 6:4, 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, LV-PVOH/TRO adjuvant wt/wt ratio is 9:1 in other embodiments, and LV-PVOH/TRO adjuvant wt/wt ratio is 19:1 in other embodiments.Term " low viscosity polyvinyl alcohol " and " LV-PVOH " are synonyms, it refers to oligomeric material or the polymer materials to the dynamic viscosity of 10mPa.s and 80 molecular fractions (mol%) to the saponification deg of 95mol% of the repeating unit, 2 millis handkerchief-second (mPa.s) with derived from ethylene alcohol, described dynamic viscosity 20 ℃ adopt 4 weight/volume percentage ratios (wt/vol%, in gram LV-PVOH weight often in the deionized water volume of milliliter) its aqueous solution measure.Preferably, dynamic viscosity is 3mPa.s to 9mPa.s, and more preferably 3.5mPa.s to 8mPa.s(as 4mPa.s to 7mPa.s), all at 20 ℃, adopt its aqueous solution of 4wt/vol% to measure.Preferably, saponification deg is 84mol% to 92mol%, and more preferably 85mol% to 90mol%(as 86.5mol% to 89.0mol%).Saponification deg is relevant with LV-PVOH, and the acetic ester functionality of LV-PVOH aforementioned mol% in inferior terminal group (penultimate) polyvinyl acetate (PVA) by saponification (as being hydrolyzed with NaOH) is prepared to obtain LV-PVOH and acetic acid (in pH and time) and to remove acetic acid (as evaporation).
The term that the application uses " the organic adjuvant of non-stick property " or " TRO adjuvant " refer to the material except PVOH, wherein said material comprises carbon atom, hydrogen atom and Sauerstoffatom and optional nitrogen-atoms, the function of wherein said material is to reduce the viscosity of LV-PVOH, preferably, also improved at least one character of LV-PVOH, described character be light transmission (as transparency, mist degree or preferably the two) or water vapor permeability, to make the present composition there is functional that independent PVOH can not have.Preferably, TRO adjuvant is the organic polymer that forms transparent non-adhesive film.In some embodiments, TRO adjuvant is carboxymethyl cellulose (CMC), polyoxyethylene glycol, Vltra tears (HPMC), Star Dri 5, methylcellulose gum or polyvinylpyrrolidone (PVP) or their combination.More preferably, TRO adjuvant is CMC.
In some embodiments, without talcum composition, also comprise following material or by following material, formed in fact: at least one other composition of non-counteracting amount, i.e. second organic adjuvant.Term " non-counteracting amount " refers to not can the aforesaid non-sticky of negative impact and the amount of average water vapor permeation rate.Preferably, described amount can negative impact character (a) and at least one (preferably the two) of character (b) yet.Preferably, described at least one other composition (second organic adjuvant) is softening agent, removable dispersion agent, surfactant (tensio-active agent) or their combination of at least two kinds.In some embodiments, softening agent and TRO adjuvant are identical compositions, and in other embodiments, they are different compositions.In some embodiments, softening agent and removable dispersion agent are identical compositions, and in other embodiments, they are different compositions.In some embodiments, softening agent and tensio-active agent are identical compositions, and in other embodiments, they are different compositions.Term " removable dispersion agent " refers to volatile matter, it contains the LV-PVOH of wide distribution and the suspension of TRO adjuvant, solution or their combination for preparation in volatile matter is effectively, described volatile matter 101 kPas of (kPa) pressure have lower than approximately 130 degrees Celsius (℃) boiling point (b.p.).Preferably, the b.p. of volatile matter is approximately 0 ℃ to approximately 115 ℃, more preferably from about 30 ℃ to 110 ℃ and still more preferably from about 34 ℃ to approximately 105 ℃, all at 101kPa.Preferably, removable dispersion agent is at 20 ℃ of liquid with 101kPa.When comprising removable dispersion agent further without talcum composition, preferably removable dispersion agent is the 50wt% to 99wt% without the gross weight of talcum composition, normally, without the 50wt% to 98wt% of the gross weight of talcum composition, described gross weight comprises the weight of removable dispersion agent.Preferably, removable dispersion agent is effectively for dissolving without talcum composition to obtain the solvent of its solution, and wherein said solution can be used for being applied in a temperature in the healthy preparation of solid.The example of preferred removable dispersion agent is acetic acid, acetone, ethanol, ethyl acetate, methyl alcohol and preferred water.Term " softening agent " refers to that effective increase is without solid or the liquid substance of the mobility of talcum composition.When comprising softening agent further without talcum composition, preferably softening agent is the 0.01wt% to 20wt% of the gross weight (weight that does not comprise any removable dispersion agent) without talcum composition.Preferably, softening agent be nonvolatile (at 101kPa pressure, have and be greater than approximately 150 degrees Celsius (℃) b.p.), from without talcum composition, remove any remove dispersion agent after, softening agent is retained in fully without in talcum composition.When using, in some embodiments, softening agent with without talcum composition, form blend, wherein do not have covalently boundly, at least some softening agent react to form covalent linkage (as by the esterification of carboxylic acid) with at least some LV-PVOH or TRO adjuvant in other embodiments.The example of preferred fluidizer is glycerine, polyoxyethylene glycol (PEG) and Yelkin TTS.The example of suitable PEG be PEG-400, PEG-3350 and business derive from Sigma-Aldrich Company, St.Louis, Missouri, USA or The Dow Chemical Company, Midland, Michigan, other PEG of USA.For example, Dow provides CARBOWAX
tMthe PEG of trade mark, its number-average molecular weight scope is 200g/mol to 8000g/mol.These PEG(are in the average Mn scope of g/mol) 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 according to the Personal Care Products Council, (predecessor is Cosmetics to these PEG, Toiletries and Fragrances Association), Washington, D.C., the PEG nomenclature that USA sets up, use International Nomenclature Cosmetic Ingredient name pact to name.In some embodiments, without talcum composition, comprise further softening agent, TRO adjuvant is the composition that is different from softening agent, and softening agent is polyoxyethylene glycol, preferred PEG-400.Term " surfactant " and " tensio-active agent " are synonyms, and it refers to the capillary material that can reduce water.When comprising tensio-active agent further without talcum composition, preferably, tensio-active agent is the 0.001wt% to 1wt% without the gross weight of talcum composition (weight that does not comprise any removable dispersion agent).Tensio-active agent is emulsifying agent, wetting agent, whipping agent, dispersion agent and antifoams by the example of functional classification.Tensio-active agent is ionogenic surfactant and nonionic surface active agent by the example of textural classification.The example of ionogenic surfactant is aniorfic surfactant (as sodium lauryl sulphate), cationic surfactant (as cetyl trimethylammonium bromide) and amphoterics (as amino acid).The example of nonionic surface active agent is fatty alcohol, polyoxypropylene glycol and polysorbate (as polyoxymethylene (20) sorbyl alcohol list grease (be polysorbate80, be called to business Tween80)).
In some embodiments, without talcum composition, comprise further glycerine or PEG as nonvolatile softening agent.In some embodiments, without talcum composition, comprise further glycerine or PEG (as non-volatile plasticisers) and polysorbate ester surfactant.In some embodiments, without talcum composition, comprise further water as removable dispersion agent, in other embodiments, without talcum composition, do not contain in fact removable dispersion agent.In some embodiments, without talcum composition comprise 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, the aqueous solution that comprises LV-PVOH, CMC, PEG and polysorbate without talcum composition in some other embodiment.In some embodiments, without talcum composition, not containing Yelkin TTS, it comprises the Yelkin TTS of lower concentration (as < 1 weight percentage (wt%)) at the most further in other embodiments.In some embodiments, without talcum composition, as described in any of aforementioned embodiments in this section, difference is that CMC is unique TRO adjuvant, without talcum composition containing HPMC, methylcellulose gum, Star Dri 5 and PVP.In some embodiments, without talcum composition as described in aforementioned embodiments in this section any (but not being front a kind of embodiment immediately), difference be CMC completely by HPMC, methylcellulose gum (as METHOCEL<sup TranNum="106">tM</sup>), Star Dri 5, PVP or their combination replace.
Preferably, healthy preparation is nutritious prod formulation, pharmaceutical dosage form or veterinary drug formulation.Preferably, formulation is unit dosage.Healthy preparation can be any physical form.The example of suitable physical form is the physical form that contains solid and contain liquid.The example of the suitable healthy preparation of solid is pearl (as unique pearl (nonpareil bead)), powder, particle, tablet (as prepared by pressed powder), capsule (as gelatine capsule or its component), capsule and pill sheet (gelcap tablet), lozenge, patch and lozenge.At least some compositions of the healthy preparation of solid are solids components.The present invention expects at least one liquid component that the healthy preparation of solid comprises small amount in some embodiments further, and it only comprises solids component in other embodiments.The feature of each solids component of the healthy preparation of solid can be unbodied, partial crystallization or crystallization.Composition of the present invention can be used as composition in the healthy preparation of solid or dressing or form film on the healthy preparation of solid preferably.The example of the suitable healthy preparation containing liquid is emulsifiable paste, elixir, emulsion, gel, washing lotion, ointment, solution (as in water) and syrup.Composition of the present invention can be used as at the composition containing in the healthy preparation of liquid.
Preferably, activeconstituents is the activeconstituents of nutritious prod, medicine or veterinary drug.Nutritious prod activeconstituents provides meals, nutrition or preventative health advantages.Activeconstituents can be solid or liquid.In some embodiments, the healthy preparation of solid comprises liquid actives, its be distributed in widely on solid excipient (as solid carrier) or among, in some other embodiment, solid active agent is distributed among liquid excipient (as liquid vehicle) widely, in other other embodiment, solid active agent be distributed in widely in solid excipient in case with its formation blend.The example of nutritious prod activeconstituents is meal supplement (as antioxidant (as trans-resveratrol), flavonoid compound (as from citrus fruit, tea, wine or cocoa beans), draft, mineral, naturally occurring amino acid and VITAMIN) and nutrient fortified food (as glycinin reinforced oat bar).Medicine or veterinary drug activeconstituents provide treatment disease health advantages (as in prophylactic treatment, increase the outbreak that reaches at least one symptom time, in palliative therapy, alleviate the seriousness of at least one symptom or be suppressed at the development of the pathology effects of the disease adjusting treatment that needs disease in the mankind of this class treatment or animal patient or deficiency disorder.) example of active constituents of medicine or veterinary drug activeconstituents is pain killer (as carprofen), Zinc metallopeptidase Zace1 (ACE) inhibitor is (as quinapril, example hydrochloric acid quinapril), microbiotic (as Azythromycin), anticonvulsive drug (as gabapentin), antidepressive (for example, Sertraline, example hydrochloric acid Sertraline), anti-fibromyalgia (anti-fibromyalgic) (for example, lyrica), antihypertensive drug (amlodipine for example, as amlodipine besylate), with the medicine that reduces cholesterol (for example, atorvastatin, as atorvastatincalcuim).
In some embodiments, healthy preparation comprises at least one the acceptable vehicle that forms mixture with activeconstituents further.Term " mixture " refers to the product being blended together.Term " acceptable vehicle " refers to and is applicable to any compound or material in healthy preparation and non-active ingredient.Preferably, acceptable vehicle is the acceptable vehicle of nutritious prod, medicine or veterinary drug.The example of the acceptable vehicle of nutritious prod, medicine or veterinary drug is carrier; Thinner; Stablizer; The adjuvant of nutritious prod, medicine and veterinary drug; With the characteristic composition of formulation, as the softgel shell for capsule (as gelatine capsule shell) with for semi-permeable membranes and the lining (backings) of transdermal patch.
In some embodiments, without talcum composition, comprise further removable dispersion agent, the method for preparing coated solid formulation has adopted removable dispersion agent further.For obtaining the dressing of the healthy preparation of solid of coated solid formulation, preferably carry out as follows: in the exposed surface application surface dressing-significant quantity of (solid) healthy preparation, (for example can remove dispersion agent, solvent, as ethanol or water) in the suspension without talcum composition or preferred solution, thereby so use without the talcum composition exposed surface of coated (solid) healthy preparation equably; With (solid) healthy preparation from coated, remove removable dispersion agent, to obtain the solid dosage of dressing.Term " surface coatings-significant quantity " refers 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).Suspension or preferably preparation by the following method of solution without talcum composition: make the dispersion agent removed (for example, solvent is as ethanol or the water) contact without talcum composition and appropriate amount, to obtain its suspension or solution.The example of contact is to stir (agitating), jolting, injection, stirring (stirring) and rolling.
Preferably, finished product comprise healthy preparation, described healthy preparation comprise activeconstituents with contact with its work without talcum composition.
Illustrative embodiment of the present invention is below provided, and wherein embodiment (comprising some preparation) has been used some method and material.Described method, material and preparation are described in next section.
LV-PVOH: refer to the Gohsei from Nippon, Osaka, the Gohsenol EG-05P of Japan.Gohsenol EG-05P has the dynamic viscosity (it is measured at 20 ℃ of aqueous solution with 4wt/vol%) of saponification deg and the 4.8mPa.s to 5.8mPa.s of 86.5mol% to 89.0mol%.
CMC: refer to Xylo-Mucine CRT-30PA, DS=0.9, lot7M650, it derives from The Dow Chemical Company, Midland, Michigan, USA.
PEG-400 and PEG-3350: refer to respectively CARBOWAX SENTRY poly(oxyethylene glycol) 400 NF, WL0101AAKC and CARBOWAX SENTRY PEG3350, derive from The Dow Chemical Company.
Polysorbate80 (Tween80): refer to enzyme grade 943317, it derives from Fisher Scientific.
Tablet: refer to placebo tablet (the red capsule label of 100g, 493g white ovals tablet, 6.5g white disk), it derives from The Dow Chemical Company.
Dynamic viscosity testing method: use Brookfield-II, D06719 is with suitable number of spindles 2,3,5 or 7 and the viscosity of corresponding 10 rpms (rpm), 20rpm, 50rpm and 100rpm test soln.
Film preparation: complete all film preparations and storage in constant temp (22 ℃) and relative humidity (50%RH) environment.Near curtain coating (traction (draw) downwards) bar edge by 1mm gap, slowly pour the solution of 20wt% into, and stably draw subsequently solution to reduce bubble and defect as far as possible, complete hand traction wet film (1mm) on sheet glass.Film on drying plate two days, takes off them in slave plate, and by one day other annealed film.To the film test membrane performance after annealing.Preferably, in taking off 4 days of film, complete whole films and test to minimize the difference between any sample and sample.When test membrane not, under steady temperature and relative humidity, between the scraps of paper, preserve film.
The testing method of film transparency: use from Gardner Laboratory Inc., Bethesda, Maryland, the Pacific Scientific PG-5500 of USA and from Zebedee Corporation, Moore, South Carolina, the film transparency of the Zebedee CL-100 test membrane of USA, the standard model of its hole by opening (open port), black and the membrane standard model advanced in years that is respectively 100%, 0% and 87 (+/-1) % transparency are proofreaied and correct.Four different positionss on each film are read the test result of transparency.The mean value of four test results of record.
Film mist degree testing method: adopt from BYK Gardner, Columbia, Maryland, USA, the Haze-gard Plus of Catalog Number4725 tests the mist degree of prepared film.With percentage ratio report mist degree reading and transmitance reading the two.The mean value of four readings of record.
By percentage ratio film mist degree and transparency value divided by the thickness in millimeter, thereby obtain the standardized film mist degree of percentage ratio and the standardized film transparency of percentage ratio.
Viscosity testing method: tablet is carried out to dressing according to appropriate embodiment hereinafter described.The viscosity of coated tablet can be to reunite each other and bonding or do not reunite each other or the qualitative vision of bonding coated tablet is observed.Preferably, viscosity is quantitative weight percentage, and it equals the weight of the reunion part (if any) of the coated tablet that the percentage with the gross weight of prepared coated tablet (weight of the weight of the coated tablet separating and the part of any reunion) recently represents.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.Sample is taken pictures with the carrying out of comparative experiments.
Water vapour permeability testing method: use " cheers " method test water vapour permeability.The calcium chloride (2.0g) of weighing adds in the wide-necked bottle of 4 ounces (120ml), makes it in 50% relative humidity (73 ℃) and with closed ring cover (hole that has therein 2.5cm diameter), lasts 1 hour.Then, at a small amount of vacuum grease of bottleneck edge placed around.Use metal stamping film to be cut into the disk of approximately 1.3 inches of (3.3 centimetres (cm)) diameters.Membrane sample disk is placed in to wide-necked bottle top, and the lid with the hole of 1 inch of (2.5cm) diameter is placed in to the top of film disk.Cover tightly lid to form sealing, and guarantee not make film disk to break.Wide-necked bottle is put into temperature-humidity chamber that Environ-Cab controller (Lab-Line Instrument, Inc.) is housed, be arranged on 75% relative humidity and 25 ℃.Record the gross weight of wide-necked bottle, lid, film and calcium chloride, within every 24 hours, redeterminate gross weight, continue 5 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/cm
2hr) water vapor of meter sees through (WVT) rate,
M wherein
tbe quality (gram (g/hr) per hour) over time, A is with square centimeter (cm
2) membrane area of exposure of meter.According to following formula, calculate membranous permeation rate:
Wherein l is thickness, and S is at 25 ℃ of water saturation vapour pressures, RH
20.75(75% relative humidity) and RH
10.S (RH
2-RH
1) be to water by the motivating force of the mass transfer of film.
With the following non-film without talcum composition of the present invention (a)-(d) compare, the film without talcum composition of the present invention can be favourable:
(a) film of 100%CMC, this film has the stdn film mist degree of 14%/mm, the stdn film transparency and 12 * 10 of 472%/mm
-7the average WVT rate of permeation of g/Pa.h.m;
(b) film of 100%Gohsenol EG-05P, this film is viscosity (when it is the reunion part of 13wt% during to tablet coating according to tablet coating step hereinafter described);
(c) film of 100%Gohsenol EG-40P (the high viscosity PVOH with the dynamic viscosity (adopting the 4wt/vol% aqueous solution to measure at 20 ℃) of saponification deg and the 40mPa.s to 46mPa.s of 86.5mol% to 89.0mol%), this film is viscosity, and it is compared with film (b) has the stdn film mist degree of remarkable increase and the stdn film transparency of decline; With
(d) film of 50:50Gohsenol EG-05P/CMC, this film has 7 * 10
-7the average water rate of permeation of g/Pa.h.m.
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, in deionization (DI) water (as 100g), dissolve whole according to the following material of following table 1: 8g to 25g(is as 10g) Gohsenol EG-05P (LV-PVOH) and CMC and optional softening agent, thereby obtain embodiment 1 to 6 separately as solution (solid of 4wt% to 15wt%) without talcum composition.Vaporize water from part solution, to obtain separately dry without talcum composition of embodiment 1 to 6, it has Gohsenol EG-05P LV-PVOH, CMC and optional softening agent as shown in table 1.
Table 1: embodiment 1-6
* wt% is the gross weight based on LV-PVOH, CMC and any softening agent.
Embodiment A-F: the tablet of dressing.In experiment separately, pack tablet into Vector Hi-Coater type LDCS, its exhaust temperature set-point is 40 ℃.Injection rate by any solution of embodiment 1-6 with 2.0 to 2.7 grams per minutes (g/min) is injected on tablet, the lasting time of calculating, to reach 1% to 3% theoretical film weightening finish, thereby obtains respectively embodiment A to F coated tablet separately.Aspect following, film and coated tablet are evaluated: viscosity, with gram every pascal-hour-meter x10
-7the average water rate of permeation of meter; Film thickness standard film transparency with every millimeter of film thickness gauge of percentage ratio transparency; Film mist degree in percentage ratio; With the film thickness stdn film mist degree with every millimeter of film thickness gauge of percent haze.
Table 2: embodiment A-F
As shown in the Examples, without talcum composition, can in solid dosage, form non-adhesive film or dressing, this film or dressing have favourable combination or characteristic beyond expectationly, and it comprises at the most 5.0 * 10<sup TranNum="157">-7</sup>the average water vapor permeation rate of g/Pa.h.m;>the stdn film transparency of 500%/mm; ≤ 13% film mist degree; In some embodiments, the stdn film mist degree of also comprise<13%/mm.The tablet of dressing has the dressing of the embodiment that comprises non-adhesive film of the present invention, and it has the thickness that is applicable to medicine, nutritious prod and the application of veterinary drug coated tablet.
Claims (12)
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 rate of permeation 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.
Claim 1 without talcum composition, it is further characterized in that the stdn film transparency at least with at least 500% every millimeter of thickness.
Claim 1 or claim 2 without talcum composition, it is further characterized in that to have 13% film mist degree at the most.
4. any one of claim 1-3 without talcum composition, it is comprised of low viscosity polyvinyl alcohol and the organic adjuvant of non-stick property in fact, and the w/w ratio in described composition is wherein said low viscosity polyvinyl alcohol with the organic adjuvant of described non-stick property >=and 60:40 is to≤95:5.
Claim 4 without talcum composition, the organic adjuvant of wherein said non-stick property is carboxymethyl cellulose, polyoxyethylene glycol, Vltra tears, Star Dri 5, methylcellulose gum or polyvinylpyrrolidone or their combination.
Claim 5 without talcum composition, the organic adjuvant of wherein said non-stick property is carboxymethyl cellulose.
Any one of aforementioned claim without talcum composition, it in fact also comprises at least one second organic adjuvant of non-counteracting amount, described second organic adjuvant is softening agent, tensio-active agent or removable dispersion agent.
Claim 7 without talcum composition, wherein said second organic adjuvant is polyoxyethylene glycol, polysorbate, water; Or the combination of polyoxyethylene glycol, polysorbate and optional water.
9. the method for preparing the solid dosage of dressing, described method comprises the contacting without talcum composition and the healthy preparation of solid that comprises activeconstituents of one of aforementioned claim that makes dressing-significant quantity, described contact is carried out in mode so, so that the healthy preparation of solid described in dressing, thereby the solid dosage of the dressing that obtains comprising non-adhesive film, described non-adhesive film comprises without talcum composition, and it exists dressing work to contact with the healthy preparation of solid.
10. finished product, any one that it comprises claim 1-8 without talcum composition.
The finished product of 11. claims 10, the solid dosage that it comprises dressing, the solid dosage of described dressing comprises and contains the described non-adhesive film without talcum composition, and the healthy preparation of described non-adhesive film and solid exists dressing work to contact, and described non-adhesive film has at the most 5.0 * 10
-7gram every pascal-hour-the average water rate of permeation of meter.
The non-adhesive film without talcum composition of 12. any one that comprise claim 1-8.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161482264P | 2011-05-04 | 2011-05-04 | |
| US61/482,264 | 2011-05-04 | ||
| PCT/US2012/034890 WO2012151089A1 (en) | 2011-05-04 | 2012-04-25 | Talc-free polyvinyl alcohol composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103517945A true CN103517945A (en) | 2014-01-15 |
| CN103517945B CN103517945B (en) | 2016-05-25 |
Family
ID=46124711
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201280021735.1A Expired - Fee Related CN103517945B (en) | 2011-05-04 | 2012-04-25 | Without the polyvinyl alcohol compositions of talcum |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP2705088A1 (en) |
| JP (1) | JP5956563B2 (en) |
| CN (1) | CN103517945B (en) |
| WO (1) | WO2012151089A1 (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP7119913B2 (en) * | 2018-10-31 | 2022-08-17 | 三菱ケミカル株式会社 | Film coating composition, solid formulation and method for producing solid formulation |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1157002A (en) * | 1994-07-12 | 1997-08-13 | 伯温德药品服务公司 | Moisture barrier film coating composition, method, and coated products |
| CN1711307A (en) * | 2002-11-15 | 2005-12-21 | 聚物股票上市公司 | Polyvinyl alcohol composition and film |
| US20070189978A1 (en) * | 2004-06-07 | 2007-08-16 | Jie Zhang | Compositions and methods for dermally treating musculoskeletal pain |
| WO2010124131A1 (en) * | 2009-04-23 | 2010-10-28 | State Of Oregon Acting By And Through The State Board Of Higher Education On Behalf Of Oregaon State University | Flexible films and methods of making and using flexible films |
| WO2010132204A1 (en) * | 2009-05-12 | 2010-11-18 | Bpsi Holdings, Llc. | Enhanced moisture barrier immediate release film coating systems and substrates coated therewith |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080274182A1 (en) | 2007-05-03 | 2008-11-06 | Regina Helena Alida Boekema | Tablet coatings made from modified carboxymethylcellulose materials |
| WO2010030735A2 (en) | 2008-09-11 | 2010-03-18 | Aethos Pharmaceuticals, Inc. | Stabilized coating for pharmaceutical formulations |
-
2012
- 2012-04-25 JP JP2014509313A patent/JP5956563B2/en not_active Expired - Fee Related
- 2012-04-25 WO PCT/US2012/034890 patent/WO2012151089A1/en active Application Filing
- 2012-04-25 EP EP12721984.8A patent/EP2705088A1/en not_active Withdrawn
- 2012-04-25 CN CN201280021735.1A patent/CN103517945B/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1157002A (en) * | 1994-07-12 | 1997-08-13 | 伯温德药品服务公司 | Moisture barrier film coating composition, method, and coated products |
| CN1711307A (en) * | 2002-11-15 | 2005-12-21 | 聚物股票上市公司 | Polyvinyl alcohol composition and film |
| US20070189978A1 (en) * | 2004-06-07 | 2007-08-16 | Jie Zhang | Compositions and methods for dermally treating musculoskeletal pain |
| WO2010124131A1 (en) * | 2009-04-23 | 2010-10-28 | State Of Oregon Acting By And Through The State Board Of Higher Education On Behalf Of Oregaon State University | Flexible films and methods of making and using flexible films |
| WO2010132204A1 (en) * | 2009-05-12 | 2010-11-18 | Bpsi Holdings, Llc. | Enhanced moisture barrier immediate release film coating systems and substrates coated therewith |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2014517100A (en) | 2014-07-17 |
| JP5956563B2 (en) | 2016-07-27 |
| EP2705088A1 (en) | 2014-03-12 |
| WO2012151089A1 (en) | 2012-11-08 |
| CN103517945B (en) | 2016-05-25 |
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