WO2012029820A1 - 医薬固形製剤用のコーティング剤、医薬用フィルム製剤及び被覆医薬固形製剤 - Google Patents
医薬固形製剤用のコーティング剤、医薬用フィルム製剤及び被覆医薬固形製剤 Download PDFInfo
- Publication number
- WO2012029820A1 WO2012029820A1 PCT/JP2011/069692 JP2011069692W WO2012029820A1 WO 2012029820 A1 WO2012029820 A1 WO 2012029820A1 JP 2011069692 W JP2011069692 W JP 2011069692W WO 2012029820 A1 WO2012029820 A1 WO 2012029820A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- coating agent
- pharmaceutical
- tablet
- solid preparation
- film
- Prior art date
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2813—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/2853—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)
Definitions
- the present invention relates to a coating agent for a pharmaceutical solid preparation, a pharmaceutical film preparation, and a coated pharmaceutical solid preparation.
- the need for gas barrier film coatings other than oxygen and water vapor includes prevention of diffusion of volatile (sublimation) drugs or decomposition products thereof. This is because when these substances are diffused, there are problems such as producing a bad odor or changing the color of other drugs when they are packaged.
- olmesartan medoxomil which is an angiotensin II receptor antagonist
- the (5-methyl-2-oxo-1,3-dioxol-4-yl) methyl group released from olmesartan medoxomil is hydrolyzed to change to diacetyl. It is known to emit a odor derived from diacetyl.
- the olmesartan medoxomil preparation is colored with the metformin hydrochloride preparation when packaged with the metformin hydrochloride preparation and stored under high temperature and high humidity conditions. This coloration is due to the reaction of diacetyl from olmesartan medoxomil with the guanidino group of metformin hydrochloride.
- Patent Document 5 a pharmaceutical package containing a chemisorption desiccant
- Patent Document 6 a film coating containing sodium carboxymethyl cellulose
- Patent Document 5 a film coating containing a polyvinyl alcohol copolymer
- JP-T-2004-518750 International Publication No. 2005/019286 JP 2006-188490 A International Publication No. 2010/074223 International Publication No. 2008/041663 International Publication No. 2006/123765 International Publication No. 2007/145191
- the sugar coating of a pharmaceutical solid preparation for the purpose of gas barrier not only takes a long time, but since the film thickness of the sugar coating increases, the pharmaceutical solid preparation itself becomes large and difficult to drink, increasing the burden on patients. Furthermore, there is a risk that it takes a long time until the medicinal effect is exhibited.
- the present invention provides a coating agent for a solid pharmaceutical preparation that does not affect the disintegration property of the pharmaceutical solid preparation while imparting an excellent gas barrier property equivalent to that of the PTP sheet to the unwrapped pharmaceutical solid preparation itself. It is intended to provide.
- the present inventors have found that a coating agent in which a swellable clay is uniformly dispersed in polyethylene glycol imparts a gas barrier property equivalent to that of a PTP sheet to a pharmaceutical solid preparation itself. It was found that the film formed from the coating agent was highly disintegratable.
- the present invention includes a polyethylene glycol having an average molecular weight of 950 to 25000 and a swellable clay, wherein the mass ratio of the polyethylene glycol to the swellable clay is 2: 8 to 6: 4.
- the coating agent is provided.
- the swellable clay has a maze-like structure, and exhibits an effect of preventing contact between the coated pharmaceutical solid preparation and water vapor or oxygen (hereinafter, “maze effect”). For this reason, even if the film layer is thin, the pharmaceutical solid preparation itself can be provided with an excellent gas barrier property equivalent to that of the PTP sheet, and the patient's dose is not hindered.
- the swellable clay is preferably bentonite or aluminum magnesium silicate.
- the coating agent preferably contains 0.5 to 30% of a sugar alcohol derivative type surfactant.
- the sugar alcohol derivative surfactant is preferably a sorbitan fatty acid ester.
- the present invention is formed from the above coating agent, and has a water vapor permeability of less than 1.0 ⁇ 10 ⁇ 4 g ⁇ mm / cm 2 ⁇ 24 hr ⁇ atm under conditions of room temperature of 40 ° C. and relative humidity of 75%.
- the water vapor permeability is less than 1.0 ⁇ 10 ⁇ 4 g ⁇ mm / cm 2 ⁇ 24 hr ⁇ atm under the conditions of a room temperature of 40 ° C. and a relative humidity of 75%.
- a coated pharmaceutical solid formulation is provided.
- the present invention includes polyethylene glycol having an average molecular weight of 950 to 25000 and a swellable clay, wherein the mass ratio of the polyethylene glycol to the swellable clay is 2: 8 to 6: 4, and a room temperature of 40 ° C.
- a pharmaceutical film preparation having a water vapor permeability of less than 1.0 ⁇ 10 ⁇ 4 g ⁇ mm / cm 2 ⁇ 24 hr ⁇ atm under a condition of 75% relative humidity, or polyethylene glycol having an average molecular weight of 950 to 25000, And a water vapor permeability of 1.0 ⁇ under the conditions of a mass ratio of polyethylene glycol to the swellable clay of 2: 8 to 6: 4, room temperature of 40 ° C. and relative humidity of 75%.
- a coated pharmaceutical solid preparation having a coating layer of less than 10 ⁇ 4 g ⁇ mm / cm 2 ⁇ 24 hr ⁇ atm.
- the pharmaceutical solid preparation itself can be provided with an excellent gas barrier property equivalent to that of a PTP sheet, thus preventing deterioration of the pharmaceutical solid preparation and stably maintaining the medicinal components for a long period of time. It becomes possible to do.
- the formed film itself is excellent in disintegrating property, the outstanding gas barrier performance can be exhibited, without affecting the disintegrating property of a pharmaceutical solid formulation.
- FIG. 1 It is an elution profile of the tablet of Example 1, the tablet of Comparative Example 4, and a commercially available tablet. It is an elution profile of the tablet of Example 2, the tablet of Comparative Example 5, and a commercially available tablet. It is an elution profile before and behind the preservation
- FIG. 2 It is an elution profile before and behind the preservation
- FIG. It is an elution profile before and after storage of a commercially available tablet. It is a focused ion beam transmission electron microscope image of the film of Example 3. It is a focused ion beam transmission electron microscope image of the film of Example 4.
- the coating agent for a solid pharmaceutical preparation of the present invention comprises polyethylene glycol having an average molecular weight of 950 to 25000 and a swellable clay, and the mass ratio of the polyethylene glycol to the swellable clay is from 2: 8 to 6: 4. It is characterized by being.
- “Pharmaceutical solid preparation” refers to a pharmaceutical formulated so as to be solid, for example, tablets (including sublingual tablets and orally disintegrating tablets), capsules (including soft capsules and microcapsules), Examples include granules, fine granules, powders, pills, troches, and film preparations.
- the “coating agent for a pharmaceutical solid preparation” refers to a composition capable of forming a thin film on the surface of the pharmaceutical solid preparation and covering the solid pharmaceutical preparation with the layer of the film.
- the above film imparts gas barrier properties to the pharmaceutical solid preparation, and plays a role of preventing decomposition or discoloration of the medicinal component contained in the pharmaceutical solid preparation due to oxygen or water vapor or deterioration of the pharmaceutical solid preparation.
- the mass of the film layer covering the pharmaceutical solid preparation is preferably 2 to 200% with respect to the weight of the pharmaceutical solid preparation itself, and preferably 3 to 70% if the pharmaceutical solid preparation is a tablet. 20% is more preferable, and 3 to 15% is more preferable.
- the coating agent for the solid pharmaceutical preparation of the present invention is sprayed or applied to the surface of the solid pharmaceutical preparation.
- the solvent contained in the coating agent may be removed by drying. More specifically, if the pharmaceutical solid preparation is in the form of a tablet, for example, use of a coating pan or a tablet coating machine can be mentioned.
- a pharmaceutical solid formulation is a granular form or a powder form, use of a fluidized bed coating machine or a rolling fluidized bed coating machine is mentioned, for example.
- Examples of the solvent contained in the coating agent include water, lower alcohols having 1 to 5 carbon atoms, and mixed solvents thereof, and ethanol or water is preferable.
- the coating agent for a pharmaceutical solid preparation of the present invention may be in a solid state as well as a liquid state.
- the solid state coating agent include those obtained by spray-drying or freeze-drying a liquid state coating agent and evaporating the solvent component.
- a film preparation can also be obtained by drying a coating agent for a pharmaceutical solid preparation of the present invention to which a medicinal component is added as it is.
- the “medicinal ingredient” contained in the solid pharmaceutical preparation means a substance that is used for the treatment, prevention and diagnosis of human and animal diseases and is not a device machine.
- a chemotherapeutic agent for example, a calcium antagonist , Antibiotics, respiratory stimulants, antitussive expectorants, antineoplastic agents, autonomic nerve agents, psychiatric agents, local anesthetics, muscle relaxants, gastrointestinal agents, antihistamines, addiction treatments, hypnotic sedatives, Antiepileptics, antipyretics, analgesics, anti-inflammatory agents, cardiotonic agents, antiarrhythmic agents, diuretics, vasodilators, antilipidemic agents, nourishing tonics, vitamins, anticoagulants, liver drugs, hypoglycemia Agent, antihypertensive agent, anticolitis agent, antiasthma agent, antianginal agent, antiemetic agent, glucocorticoid, ulcerative colitis or Crohn's disease agent, anti
- the excellent gas barrier property obtained by the coating agent for a pharmaceutical solid preparation of the present invention exhibits its effect particularly well in the coating of a pharmaceutical solid preparation containing hygroscopic, oxidatively degradable or odorous medicinal ingredients. It is.
- Degradation of a pharmaceutical solid preparation means, for example, a change in the weight, hardness or shape of a pharmaceutical solid preparation due to oxygen or water vapor, a decrease in content due to decomposition of medicinal ingredients, leakage, cracking or coloring of the surface of the pharmaceutical solid preparation, etc. Changes in appearance can be mentioned.
- PEG Polyethylene glycol
- Polyether polymer compound having a structure in which ethylene glycol is polymerized.
- polyether polymer compound having a structure in which ethylene glycol is polymerized.
- glycol the name of the PEG product name is the Japanese Pharmacopoeia (hereinafter sometimes abbreviated as JP).
- JP Japanese Pharmacopoeia
- the average molecular weight of PEG in the present invention is required to be 950 to 25000 (eg, JP Macrogol 1000, 4000, 6000 and 20000 (Nippon Oil Co., Ltd.
- 7000-9300 for example, JP Macrogol 6000
- “Swellable clay” refers to clay having swelling properties, and specifically, it has swelling properties among fine powder substances that exhibit viscosity and plasticity when containing an appropriate amount of water. It means a substance.
- the swellable clay is preferably negatively charged due to the compositional balance of the metal salt species, but examples of the swellable clay charged negatively include smectite having a three-layer structure. It is done.
- Charge to negative charge means a state in which the swellable clay has a cation exchange capacity, and the charge amount is expressed as a cation exchange capacity (CEC).
- CEC cation exchange capacity
- the unit of cation exchange capacity is milliequivalent / 100 grams (hereinafter, “meq / 100 g”), and is generally expressed as the number of equivalents corresponding to the molar concentration of monovalent ions.
- smectite examples include beidellite, nontronite, saponite, hectorite, soconite, bentonite (hereinafter “BT”), magnesium aluminum silicate, or a mixture thereof, but BT or magnesium aluminum silicate is preferable. BT is more preferable.
- the swellable clay is uniformly dispersed in the film formed from the coating agent for a pharmaceutical solid preparation. “Uniformly dispersed” is most preferably a state in which the swellable clay is dispersed as a single-layered belt-like structure, but it is difficult to exfoliate into a single layer in a production device usually used for pharmaceutical production.
- the swellable clay is preferably dispersed as a band-like laminated structure in which the band-like structures are stacked by 10 to 100 layers, and the number of the laminated layers is preferably smaller.
- the above-mentioned band-like laminated structure is dispersed in a network and is plane-oriented.
- the state of the band-like laminated structure in the cross section in the thickness direction of the film can be observed using a transmission electron microscope (hereinafter “TEM”) or the like.
- “Surface orientation” means a state in which strip-like structures of swellable clay are stacked in the thickness direction of the film.
- the swellable clay contained in the coating agent is preferably in a swollen state.
- the “swelled state” of the swellable clay means a state in which the swellable clay contains a dispersion medium and swells.
- examples of the swellable clay in a swollen state include a dispersion obtained by suspending a swellable clay in a dispersion medium and stirring with a homogenizer or the like.
- the dispersion is filtered, all the swellable clay is filtered. It is preferable that it is in a dispersed state to the extent that it can pass through.
- glass fiber filter paper GF / D Particle retention ability 2.7 micrometers (Whatman) is mentioned, for example.
- the haze value may be mentioned as an indicator of the degree of dispersion of the swellable clay strip-like laminated structure contained in the coating agent for a pharmaceutical solid preparation of the present invention.
- the haze value is a value indicating the turbidity of the coating agent, and the value decreases as the swellable clay is uniformly dispersed and the transparency of the coating agent increases. That is, a smaller haze value of the coating agent indicates that the number of laminated layers of the swellable clay band structure is smaller.
- the swellable clay contained in the coating agent for a pharmaceutical solid preparation of the present invention preferably has a haze value of 90% or less, and 60% or less of a 3.5% aqueous solution of the swellable clay alone. Is more preferable.
- the mass ratio of PEG to swellable clay in the coating agent for solid pharmaceutical preparations of the present invention needs to be 2: 8 to 6: 4, but is preferably 3: 7.
- the mass of the swellable clay is less than 40% with respect to the mass of PEG, the labyrinth effect by the swellable clay is reduced, and an excellent gas barrier property equivalent to that of the PTP sheet cannot be obtained.
- the mass of the swellable clay exceeds 4 times the mass of the PEG, the ratio of the swellable clay is too high, so that the dispersion of the swellable clay as a strip-like laminated structure becomes non-uniform, and again the PTP sheet This is because an excellent gas barrier property equivalent to the above cannot be obtained.
- the ratio of the swellable clay in the film formed from the coating agent for a pharmaceutical solid preparation is preferably 20% or more.
- the water vapor permeability of the film formed from the coating agent for a solid pharmaceutical preparation of the present invention is 1.0 ⁇ 10 ⁇ 5 to 1.0 ⁇ 10 ⁇ 4 g ⁇ mm / cm 2 ⁇ 24 hr ⁇ atm equivalent to that of the PTP sheet.
- 1.0 ⁇ 10 ⁇ 5 to 6.5 ⁇ 10 ⁇ 5 g ⁇ mm / cm 2 ⁇ 24 hr ⁇ atm is more preferable, and 1.0 ⁇ 10 ⁇ 5 to 3.0 ⁇ More preferably, it is 10 ⁇ 5 g ⁇ mm / cm 2 ⁇ 24 hr ⁇ atm.
- the film formed from the coating agent for a pharmaceutical solid preparation of the present invention exhibits excellent disintegration properties. More specifically, in a dissolution test of a film formed in a size of 1 cm ⁇ 2 cm and a thickness of 60 ⁇ m (37 ° C., paddle method, 50 rotations / minute, solvent 900 ml of water), the film collapses within 10 minutes, Its shape disappears.
- the swellable clay In order to uniformly disperse the swellable clay in the film, it is important to disperse the swellable clay uniformly in the coating agent solution.
- the swellable clay As a dispersing device, the swellable clay is uniformly dispersed as a belt-like laminated structure.
- An apparatus having a stirring ability that can be used is preferable.
- a homogenizer Polytron; Kinematica
- a thin-film swirl type high-speed stirrer Frmix: Primix
- the coating agent for solid pharmaceutical preparations of the present invention may contain pharmaceutically acceptable additives as long as the gas barrier property is not lowered.
- a surfactant may be included as an additive in order to make the dispersion of the swellable clay as a strip-shaped laminated structure more uniform, but the amount of the surfactant relative to the total amount of PEG and swellable clay in this case Is preferably 0.01 to 30 parts by mass, more preferably 1 to 20 parts by mass, and even more preferably 5 to 15 parts by mass.
- sugar alcohol derivative type surfactant As the surfactant, a sugar alcohol derivative type surfactant is preferable.
- the “sugar alcohol derivative-type surfactant” refers to a compound having a sugar alcohol skeleton in the molecule and having a surface activity, and among them, sorbitan fatty acid esters are preferable. Examples of sorbitan fatty acid esters include sorbitan monolaurate.
- the coating agent for a pharmaceutical solid preparation of the present invention preferably contains 0.5 to 30% of a sugar alcohol derivative surfactant.
- the coating agent for a solid pharmaceutical preparation of the present invention may further contain an additive generally used for coating in the pharmaceutical field.
- an additive include a shielding agent.
- Coloring agents such as certain plant extract pigments, titanium oxide, calcium carbonate or silicon dioxide.
- the pharmaceutical solid preparation coated with the film layer formed from the coating agent for the pharmaceutical solid preparation of the present invention may be pre-coated with the film layer formed from other polymer substance, etc.
- the ratio of the swellable clay to the whole film layer of the pharmaceutical solid preparation is preferably 5% or more.
- a film formed with an appropriately prepared coating agent is watermarked in light, a portion having a uniform thickness without a pinhole is selected, and is cut into a circular shape so that the diameter becomes 3.5 cm, and any five locations The film thickness was measured.
- 3 g of calcium chloride (particle size of 850 to 2000 ⁇ m) is put in an aluminum cup (diameter 30 mm), a film cut in a circle and a film fixing ring are placed on the aluminum cup in order, and a weight is placed on the ring. The ring was fixed by placing it, and the paraffin wax melted in that state was poured into the edge of the aluminum cup.
- the oxygen permeation coefficient of the film formed from the coating agent for a pharmaceutical solid preparation of the present invention is based on the gas permeation test method according to JIS K7126-1 (2006) gas chromatograph method (GTR-30XAD2G and 2700T. F: GTR Tech Co.) and a temperature of 23 ⁇ 2 ° C. and a relative humidity of 90% (90% RH).
- the dissolution test is conducted in accordance with the 15th revised Japanese Pharmacopoeia Dissolution Test Method 2 and the second solution of JP Dissolution Test is used as the test solution.
- the tablets are put into 900 mL of the test solution and the dissolution solution is collected over time. Quantification was performed under the following HPLC conditions.
- Example 1 445.1 parts by weight of water, 10.5 parts by weight of PEG (Macrogol 6000 (average molecular weight 7300-9300); NOF Corporation), 544.4 parts by weight of 4.5% BT solution and 3.5 parts by weight Of Span 20 was added and stirred with a homogenizer (Polytron (registered trademark) Model KR) to obtain a coating agent (hereinafter referred to as “Example 1 coating agent”).
- a homogenizer Polytron (registered trademark) Model KR
- Example 1 coating agent 45 parts by mass of BT (Kunipia-F (cation exchange capacity: 115 meq / 100 g); Kunimine Industries) was added to 955 parts by mass of stirred water and uniformly dispersed with a homogenizer. Thereafter, the resultant was centrifuged, and the supernatant obtained by suction filtration with a filter paper was used.
- sodium valproate tablet (Depaken (registered trademark) 200 mg; Kyowa Hakko Kirin Co., Ltd.) and 200 g of placebo tablet (for bulking) were charged into a coating pan (DRC-200; Paulek Co., Ltd.), and the film thickness was 50-
- the sodium valproate agent was coated with the coating agent of Example 1 until the thickness became 60 ⁇ m.
- the coated sodium valproate tablets thus obtained were stored for 12 days under conditions of 40 ° C. and 75% relative humidity, and changes in appearance and dissolution profiles before and after storage were examined.
- Example 1 the coating agent of Example 1 was sprayed on the back surface of the polypropylene balance tray and immediately dried with hot air from a dryer. After repeating these operations several times, the balance tray was left still in an oven at 50 ° C. and dried overnight, and the water vapor permeability of the film peeled from the balance tray was measured.
- Example 2 20 g of Montelukast sodium tablet (Singlea (registered trademark) 10 mg; Ariyu Pharmaceutical Co., Ltd.) and 230 g of placebo tablet (for bulking) were charged into a coating pan (DRC-200; Paulek), and the film thickness was adjusted to 60-80 ⁇ m. Until then, montelukast sodium tablets were coated with the coating agent of Example 1. The coated montelukast sodium tablets thus obtained were stored at 40 ° C. and a relative humidity of 75% for 1 week, and the dissolution profiles and the increase in moisture absorption before and after storage were examined.
- Example 3 To 111.95 parts by weight of water, 5.25 parts by weight of PEG (Macrogol 6000; NOF Corporation) and 382.8 parts by weight of a 3.2% BT solution are added and stirred with a homogenizer to form a coating agent (hereinafter referred to as “the coating agent”). "Example 3 coating agent”) was obtained.
- the coating agent As a 3.2% BT solution, 32 parts by weight of BT (Kunipia-F; Kunimine Industries) was added to 968 parts by weight of stirred water, and the mixture was uniformly dispersed with a homogenizer and then centrifuged. The filtrate obtained by suction filtration through filter paper was used.
- Example 3 Thereafter, the coating agent of Example 3 was sprayed on the back surface of the polypropylene balance tray and immediately dried with hot air from a dryer. After repeating these operations several times, the balance tray was allowed to stand in an oven at 50 ° C. and dried overnight, the film was peeled off from the balance tray, and the water vapor permeability was measured. Further, the haze value of the coating agent of Example 3 was measured.
- Example 4 Coating agent obtained by adding 5.25 parts by mass of PEG (Macrogol 6000; NOF Corporation) and 272.2 parts by mass of 4.5% BT solution to 222.55 parts by mass of water and stirring with a homogenizer (Hereinafter referred to as “Example 4 coating agent”), a film was formed in the same manner as in Example 1, and the water vapor permeability and oxygen permeability coefficient were measured. Further, the haze value of Example 4 coating agent was measured.
- Example 5 Add 5.25 parts by mass of PEG (Macrogol 1000 (average molecular weight 950 to 1050); NOF Corporation) and 272.2 parts by mass of 4.5% BT solution to 222.55 parts by mass of water, and stir with a homogenizer. Using the coating agent thus obtained, a film was formed in the same manner as in Example 1, and the water vapor permeability was measured.
- PEG Microgol 1000 (average molecular weight 950 to 1050); NOF Corporation)
- BT solution 272.2 parts by mass of 4.5% BT solution
- Example 6 Add 5.25 parts by mass of PEG (Macrogol 4000 (average molecular weight 2600-3800; NOF Corporation) and 272.2 parts by mass of 4.5% BT solution to 222.55 parts by mass of water, and stir with a homogenizer. A film was formed using the coating agent obtained in the same manner as in Example 1, and the water vapor permeability was measured.
- PEG Microgol 4000 (average molecular weight 2600-3800; NOF Corporation)
- BT solution 222.55 parts by mass of water
- Example 7 Add 5.25 parts by mass of PEG (Macrogol 20000 (average molecular weight 20000 to 25000); NOF Corporation) and 272.2 parts by mass of 4.5% BT solution to 222.55 parts by mass of water, and stir with a homogenizer. A film was formed in the same manner as in Example 1 using the coating agent thus obtained, and its water vapor permeability was measured.
- PEG Microgol 20000 (average molecular weight 20000 to 25000); NOF Corporation)
- BT solution 272.2 parts by mass of 4.5% BT solution
- Example 8 A coating agent obtained by adding 10.5 parts by mass of PEG (Macrogol 6000; NOF Corporation) and 155.56 parts by mass of a 4.5% BT solution to 333.94 parts by mass of water and stirring with a homogenizer A film was formed in the same manner as in Example 1, and the water vapor permeability was measured.
- Example 9 A coating agent obtained by adding 3.5 parts by mass of PEG (Macrogol 6000; NOF Corporation) and 437.5 parts by mass of 3.2% BT solution to 59.0 parts by mass of water and stirring with a homogenizer A film was formed in the same manner as in Example 1, and the water vapor permeability was measured.
- PEG Microgol 6000; NOF Corporation
- Example 10 Add 4.62 parts by weight of PEG (Macrogol 6000; NOF Corporation), 156.9 parts by weight of water, 336.9 parts by weight of a 3.2% BT solution and 2.1 parts by weight of Span 80, and use a homogenizer. Using the coating agent obtained by stirring, a film was formed in the same manner as in Example 1, and the water vapor permeability was measured.
- PEG Microgol 6000; NOF Corporation
- Example 11 In 156.38 parts by weight of water, 4.62 parts by weight of PEG (Macrogol 6000; NOF Corporation), 336.9 parts by weight of 3.2% BT solution and 2.1 parts by weight of Tween 80 (polysorbate 80). In addition, a film was formed in the same manner as in Example 1 using the coating agent obtained by stirring with a homogenizer, and the water vapor permeability was measured.
- PEG Microgol 6000; NOF Corporation
- Tween 80 polysorbate 80
- Example 12 To 112.0 parts by mass of water, 5.075 parts by mass of PEG (Macrogol 6000; NOF Corporation), 382.8 parts by mass of a 3.2% BT solution and 0.175 parts by mass of liquid paraffin were added, and a homogenizer was added. A film was formed in the same manner as in Example 1 using the coating agent obtained by stirring in step 1, and the water vapor permeability was measured.
- PEG Microgol 6000; NOF Corporation
- Example 13 Add 10.5 parts by mass of PEG (Macrogol 6000; NOF Corporation) to 544.4 parts by mass of 4.5% BT solution, and stir with a homogenizer. 3.5 parts by mass of Span 20 and 531.15 parts by mass Then, 450.45 parts by mass of ethanol was added and stirred again with a homogenizer to obtain a coating agent (hereinafter referred to as “Example 13 coating agent”).
- a coating agent hereinafter referred to as “Example 13 coating agent”.
- Montelukast sodium tablets (Singlea (registered trademark) tablets 10 mg; Ashi Pharmaceutical Co., Ltd.) and 230 g of placebo tablets (for bulking) were each charged into a coating pan (DRC-200; Paulek), and the film thickness was 60 Montelukast sodium tablets were coated with the coating agent of Example 13 until ⁇ 80 ⁇ m.
- the coated montelukast sodium tablets thus obtained were stored at 40 ° C. and a relative humidity of 75% for 1 week, and the amount of increase in moisture absorption before and after storage was measured.
- Example 13 the coating agent of Example 13 was sprayed on the back surface of the polypropylene balance tray and immediately dried with hot air from a dryer. After repeating these operations several times, the balance tray was allowed to stand in an oven at 50 ° C. and dried overnight, the film was peeled off from the balance tray, and the water vapor permeability was measured.
- Example 14 Add 12.46 parts by mass of PEG (Macrogol 6000; NOF Corporation) to 127.4 parts by mass of 4.5% BT solution, stir, 0.81 parts by mass of Span 20 and 98.84 parts by mass of water. Subsequently, 225.55 parts by mass of ethanol was added, and using the coating agent obtained by stirring with a homogenizer, a film was formed in the same manner as in Example 1, and the water vapor permeability was measured.
- PEG Microgol 6000; NOF Corporation
- Example 15 1.47 parts by mass of PEG (Macrogol 6000; NOF Corporation) was added to 76.23 parts by mass of 4.5% BT solution and stirred, and 2.10 parts by mass of Span 20 and 120.2 parts by mass of water. A film was formed by the same method as in Example 1 using the coating agent obtained by stirring with a homogenizer, and the water vapor permeability was measured.
- Example 16 1.12 parts by weight of BT, 0.47 parts by weight of PEG 6000, 0.16 parts by weight of Span 20 and 28.2 parts by weight of water were added to a high-speed stirrer (Filmix 40-40 type; Primix) (hereinafter “ The mixture was mixed and stirred for 5 minutes, and then 20.0 parts by mass of water was added and stirred with a stirrer.
- the coating agent obtained by suction filtration with filter paper was used in the same manner as in Example 1. A film was formed by the method, and its water vapor permeability was measured.
- Example 17 22.4 parts by weight of a 5.0% BT solution and 0.47 parts by weight of PEG 6000 were mixed and stirred for 5 minutes using a fill mix, 0.16 parts by weight of Span 20 was added, and the mixture was further stirred for 5 minutes.
- a film was formed in the same manner as in Example 1 using a coating agent obtained by adding 26.97 parts by mass of water and stirring with a stirrer using a filter paper, and the water vapor permeability was measured.
- As the 5.0% BT solution a solution obtained by stirring 1.25 parts by mass of BT and 23.75 parts by mass of water with a fill mix was used.
- the commercially available tablet is a flat-shaped uncoated tablet and is unsuitable for film coating, so it was pulverized and re-compressed into an R tablet.
- a commercially available tablet containing olmesartan medoxomil (Olmetec Tablets (registered trademark) 20 mg; Daiichi Sankyosha) was pulverized with a mortar, and the resulting pulverized product was compressed again with a rotary tableting machine to obtain olmesartan medoxomil core tablet. (Diameter 7 mm, 10R).
- Example 18 The olmesartan medoxomil core tablet obtained by the above production method was charged into a coating pan (DRC-200; Paulek), and the coating agent of Example 1 was coated on the olmesartan medoxomil core tablet until the thickness of the film reached 60 to 80 ⁇ m.
- the coated olmesartan medoxomil tablet thus obtained and a commercially available metformin hydrochloride-containing tablet are each put in the same glass bottle and covered with a plastic cap, under conditions of 40 ° C. and relative humidity of 75%. Then, the color change of the metformin hydrochloride-containing tablet due to diacetyl which was decomposed and released from olmesartan medoxomil during storage was evaluated with a color difference meter.
- Comparative Example 1 Coating agent obtained by adding 12.25 parts by mass of PEG (Macrogol 6000; NOF Corporation) and 164.1 parts by mass of 3.2% BT solution to 323.65 parts by mass of water and stirring with a homogenizer A film was formed in the same manner as in Example 1, and the water vapor permeability was measured.
- PEG Microgol 6000; NOF Corporation
- Comparative Example 2 A coating agent obtained by adding 1.75 parts by mass of PEG (Macrogol 6000; NOF Corporation) and 492.2 parts by mass of a 3.2% BT solution to 6.05 parts by mass of water and stirring with a homogenizer. Thus, a film was formed in the same manner as in Example 1, and the water vapor permeability was measured.
- PEG Microgol 6000; NOF Corporation
- Example 3 (Comparative Example 3) Add 5.25 parts by weight of polyethylene oxide (PolyOX80; Dow Corning; hereinafter referred to as “PEO”) and 382.8 parts by weight of 3.2% BT solution to 111.95 parts by weight of water, and stir with a homogenizer. Using the obtained coating agent, a film was formed in the same manner as in Example 1, and the water vapor permeability was measured.
- PEO polyethylene oxide
- Example 4 A gas barrier coating agent described in Example 2 of Patent Document 4 was prepared. In 156.38 parts by mass of water, 4.62 parts by mass of polyvinyl alcohol (Gosenol EG05; Nippon Synthetic Chemical Co., Ltd .; hereinafter referred to as “PVA”), 336.9 parts by mass of a 3.2% BT solution and 2.1 parts by mass Span20 (sorbitan monolaurate) was added and stirred with a homogenizer to obtain a coating agent (hereinafter referred to as “Comparative Example 4 coating agent”).
- PVA polyvinyl alcohol
- Span20 sorbitan monolaurate
- Example 4 25 g of sodium valproate tablet (Depaken Tablet (registered trademark) 200 mg; Kyowa Hakko Kirin Co., Ltd.) and 225 g of placebo tablet (for bulking) were charged into a coating pan (DRC-200; Paulek Co., Ltd.), and the film thickness was 50-
- the sodium valproate tablet was coated with the coating agent of Comparative Example 4 until the thickness became 60 ⁇ m.
- the coated sodium valproate tablets thus obtained were stored for 12 days under conditions of 40 ° C. and 75% relative humidity, and changes in appearance and dissolution profiles before and after storage were examined.
- the film was formed by the same method as Example 1, and the water vapor permeability was measured.
- Comparative Example 5 20 g of Montelukast sodium tablets (Singlea tablet (registered trademark) 10 mg; Ashi Pharmaceutical) and 230 g of placebo tablets (for bulking) were charged into a coating pan (DRC-200; Paulek), and the film thickness was adjusted to 50 to 60 ⁇ m. Until then, Comparative Example 4 was coated on Montelukast sodium tablets. The coated montelukast sodium tablets thus obtained were stored at 40 ° C. and a relative humidity of 75% for 1 week, and the dissolution profiles before and after storage were examined.
- Example 7 1.26 parts by mass of PEG (Macrogol 6000; NOF Corporation) was added to 65.34 parts by mass of 4.5% BT solution and stirred, and 2.80 parts by mass of Span 20 and 130.6 parts by mass of A film was formed in the same manner as in Example 1 using the coating agent obtained by adding water and stirring with a homogenizer, and the water vapor permeability was measured.
- PEG Microgol 6000; NOF Corporation
- Example 8 A gas barrier coating agent described in Example 2 of Patent Document 6 was prepared. 15.0 parts by weight of dextrose (Japanese Pharmacopoeia Glucose NG-TDA; Sanei Saccharification Co., Ltd.) and 35 parts by weight of sodium carboxymethylcellulose (TPT-JP 50: Gotoku Pharmaceutical Co., Ltd.) are added to 1200 parts by weight of water. And dissolved by stirring to obtain a coating agent (hereinafter referred to as “Comparative Example 8 coating agent”).
- dextrose Japanese Pharmacopoeia Glucose NG-TDA; Sanei Saccharification Co., Ltd.
- TPT-JP 50 Gotoku Pharmaceutical Co., Ltd.
- Olmesartan medoxomil core tablet (diameter 7 mm, 10R) was charged into a coating pan (DRC-200; Paulek), and the olmesartan medoxomil core tablet was coated with a coating of Comparative Example 8 until the film thickness reached 60 to 80 ⁇ m.
- the coated olmesartan medoxomil tablet thus obtained and a commercially available metformin hydrochloride-containing tablet (Glycolane Tablets (registered trademark) 250 mg; Nippon Shinyaku Co., Ltd.) are placed in the same glass bottle and covered with a plastic cap under the conditions of 40 ° C. and 75% relative humidity.
- the color change of the metformin hydrochloride-containing tablet due to diacetyl released from olmesartan medoxomil during storage was evaluated with a color difference meter.
- Table 1 shows the haze values of Example 3 coating agent and Example 4 coating agent.
- Table 2 shows the mass ratio of PEG, the mass ratio of BT, the mass ratio of the third component, and the BT solution used for the preparation in each coating agent prepared in Examples 1 and 3 to 12 and Comparative Examples 1 to 4. The concentration and the water vapor permeability of each film measured in Examples 1 and 3 to 12 and Comparative Examples 1 to 4 are shown.
- the oxygen permeability coefficient of the film formed in Example 4 is 1.4 ⁇ 10 ⁇ 5 cm 3 ⁇ mm / cm 2 ⁇ 24 hr ⁇ atm, and 1.0 ⁇ 10 ⁇ 4 cm 3 ⁇ mm / cm 2 ⁇ 24 hr. -It was less than atm. From this result, it was clarified that the film formed by the coating agent for the pharmaceutical solid preparation of the present invention has excellent gas barrier properties equivalent to the PTP sheet not only against water vapor but also against oxygen. .
- Table 3 shows the results of appearance observation of the tablet of Example 1, the tablet of Comparative Example 4, and the commercially available sodium valproate tablet.
- the tablet of Comparative Example 4 showed almost no drug dissolution even after 45 minutes, but the tablet of Example 1 and the commercially available sodium valproate tablet showed dissolution of almost 100%. . From these results, even if a film layer is formed on the surface of the pharmaceutical solid preparation using the coating agent for the pharmaceutical solid preparation of the present invention and the pharmaceutical solid preparation is coated, the disintegration property of the pharmaceutical solid preparation itself is not at all. It has become clear that there is no adverse effect. In addition, about the commercially available sodium valproate tablet after a preservation
- the tablet described in Patent Document 4 represented by Comparative Example 4 has a gas barrier property but has a significant dissolution delay as compared with the tablet of the present invention shown in Example 1. Therefore, the tablet of the present invention It was revealed that is superior to the tablet described in Patent Document 4 as a pharmaceutical product.
- FIG. 2 The dissolution profiles of the tablet of Example 2, the tablet of Comparative Example 5 and the commercially available montelukast sodium tablet are shown in FIG. 2 (FIGS. 2-1, 2-2, 2-3 and 2-4).
- Table 4 shows the water vapor permeability of the films of Example 13 and Example 14 using ethanol as the dissolution solvent for the coating agent
- Table 5 shows the coated montelukast sodium-containing tablets of Examples 2 and 13 at 40 ° C. The increase in moisture absorption after storage at 75% RH is shown.
- the water vapor permeability of the films of Example 13 and Example 14 using ethanol as a dissolution solvent is less than 1.0 ⁇ 10 ⁇ 4 cm 3 ⁇ mm / cm 2 ⁇ 24 hr ⁇ atm, It became clear that the gas barrier property equivalent to a PTP sheet can be provided to the pharmaceutical solid preparation itself as in Example 1 where the dissolving solvent is water.
- the water vapor permeability was 8.6 ⁇ 10 ⁇ 6 , indicating a very high gas barrier property.
- the commercially available tablet which is a reference example has an increase in moisture absorption of 3.9%, whereas the coated montelukast sodium-containing tablet of Example 2 using water as the coating solvent is 2.5%. %,
- the coated montelukast sodium-containing tablet of Example 13 was 1.6%, and it was revealed that the coating agent of the present invention imparts high gas barrier performance to a solid pharmaceutical preparation.
- Table 6 shows the water vapor permeability of a film prepared using PEG 1000 (Example 5) and a film prepared using PEG 400 (Comparative Example 6).
- the water vapor permeability of the film of Comparative Example 6 using PEG having a molecular weight distribution of 380 to 420 was 1.0 ⁇ 10 ⁇ 4 cm 3 ⁇ mm / cm 2 ⁇ 24 hr ⁇ atm or more, but the molecular weight distribution was 950. Since the water vapor permeability of the film of Example 5 using PEG of ⁇ 1050 was less than 1.0 ⁇ 10 ⁇ 4 cm 3 ⁇ mm / cm 2 ⁇ 24 hr ⁇ atm, the pharmaceutical solid preparation was equivalent to the PTP packaging sheet It was suggested that the molecular weight distribution of PEG needs to be 950 or more in order to maintain the gas barrier performance.
- Table 7 shows the water vapor permeability of films having different mass ratios of the third component in the coating agent.
- the water vapor permeability of the film of Example 15 in which the mass ratio of the third component was 30% was less than 1.0 ⁇ 10 ⁇ 4 cm 3 ⁇ mm / cm 2 ⁇ 24 hr ⁇ atm. Since the water vapor permeability of the film of Comparative Example 7 having a mass ratio of 40% was 1.0 ⁇ 10 ⁇ 4 cm 3 ⁇ mm / cm 2 ⁇ 24 hr ⁇ atm or more, it was equivalent to a PTP packaging sheet as a pharmaceutical solid preparation In order to maintain the gas barrier performance, it was suggested that the mass ratio of the third component added to the coating agent needs to be 30% or less.
- Table 8 shows the water vapor permeability of a film formed using a coating agent prepared using a fill mix.
- the coating agent was prepared.
- the stirrer / disperser used in the process is not limited to a homogenizer (Polytron; Kinematica), but if the apparatus can disperse the coating agent to the extent that it can be suction filtered with filter paper, the composition is added in a liquid state or a solid state such as a powder. Even so, it has been clarified that a coating agent can be prepared that allows the solid pharmaceutical preparation to maintain the same gas barrier performance as the PTP packaging sheet.
- Table 9 shows the set of the coated olmesartan medoxomil tablet of Example 18 and a commercially available metformin hydrochloride-containing tablet, the set of a gas barrier coating agent of Comparative Example 8 and a commercially available metformin hydrochloride-containing tablet, or the commercially available olmesartan of Reference Example 4.
- a set of medoxomil-containing tablets and commercially available metformin hydrochloride-containing tablets are each placed in the same bottle and stored at 40 ° C. and 75% RH for 1 week, and the color difference of the metformin hydrochloride-containing tablets before and after storage is stored in a color difference meter. The ⁇ E obtained through evaluation is shown.
- the coating agent for a pharmaceutical solid preparation of the present invention can be suitably used in the pharmaceutical field to form a film layer that covers the pharmaceutical solid preparation.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Inorganic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
本発明の医薬固形製剤用のコーティング剤により形成したフィルムの水蒸気透過度は、JIS K8123(1994)を一部改変して測定した。
水蒸気透過度(g・mm/cm2・24hr・atm)=(W×A)/(B×t×C)
W: 24時間で増加した質量(g)
A: 5箇所のフィルムの厚みの平均値(mm)
B: 透過面積πr2(cm2)
t: 経過時間(時間)
C: 気圧(atm)
積分球分光光度計(UV-3101PC型自記分光光度計;島津製作所)を用いて全光線透過スペクトル及び拡散透過スペクトルを測定し、ヘーズ値を算出した。
本発明の医薬固形製剤用のコーティング剤により形成したフィルムの酸素透過係数は、JIS K7126-1(2006)ガスクロマトグラフ法によるガス透過試験方法に基づき、酸素透過係数測定装置(GTR-30XAD2G及び2700T.F;GTRテック社)を使用して、23±2℃の温度で90%相対湿度(90%RH)の条件で測定した。
溶出試験は、第十五改訂日本薬局方溶出試験法第二法に従って行い、日局溶出試験第2液を試験液とし、試験液900mLに錠剤を投入し、経時的に溶出液を採取して下記HPLC条件で定量した。
移動相 : 50mMリン酸二水素ナトリウム/アセトニトリル=5/5(v/v)
カラム : Devolosil ODS-5(4.6×150mm)
検出波長: 210nm
溶出試験は、第十五改訂日本薬局方溶出試験法第二法に従って行い、蒸留水に0.5%濃度のポリソルベート80を添加した試験液(900mL)に錠剤を投入し、経時的に溶出液を採取して下記のHPLC条件で定量した。
移動相 : 酢酸塩緩衝液(pH3.5)/メタノール=15/85(v/v)
カラム : Hypersil ODS(4.6×250mm)
検出波長: 254nm
保存前錠剤及び保存後錠剤の質量を測定し、以下の式1によって吸湿増加量を算出した。
吸湿増加量(質量%)={(W-Ws)/Ws}×100 ・・・・・・式1
W : 保存後錠剤の質量(g)
Ws: 保存前錠剤の質量(g)
分光色彩計(JP7100F/C;JUKI社)を用いてL*、a*、b*を測定し、保存前の錠剤との色差(ΔE)を以下の式2から算出した。
ΔE={(ΔL)2+(Δa)2+(Δb)2}0.5・・・・・・式2
ΔL:保存前後の錠剤の明るさ(L*軸)の値の差
Δa:保存前後の錠剤の赤~緑(a*軸)の値の差
Δb:保存前後の錠剤の黄~青(b*軸)の値の差
445.1質量部の水に10.5質量部のPEG(マクロゴール6000(平均分子量7300~9300);日油社)、544.4質量部の4.5%BT溶液及び3.5質量部のSpan20を加え、ホモジナイザー(ポリトロン(登録商標) Model KR)で撹拌してコーティング剤(以下、「実施例1コーティング剤」)を得た。なお、4.5%BT溶液としては、撹拌した955質量部の水に45質量部のBT(クニピア‐F(カチオン交換能:115meq/100g);クニミネ工業)を添加し、ホモジナイザーで均一分散させた後に遠心分離し、その上澄み液を濾紙で吸引濾過して得られた濾液を用いた。
20gのモンテルカストナトリウム錠(シングレア(登録商標)錠10mg;萬有製薬)及び230gのプラセボ錠(嵩増し用)をコーティングパン(DRC-200;パウレック社)に仕込み、フィルムの厚みが60~80μmになるまで実施例1コーティング剤でモンテルカストナトリウム錠を被覆した。こうして得られた被覆モンテルカストナトリウム錠を40℃、相対湿度75%の条件下で1週間保存し、保存前後における溶出プロファイルと吸湿増加量を調べた。
111.95質量部の水に5.25質量部のPEG(マクロゴール6000;日油社)及び382.8質量部の3.2%BT溶液を加え、ホモジナイザーで撹拌してコーティング剤(以下、「実施例3コーティング剤」)を得た。なお、3.2%BT溶液としては、撹拌した968質量部の水に32質量部のBT(クニピア‐F;クニミネ工業)を添加し、ホモジナイザーで均一分散させた後に遠心分離し、その上澄み液を濾紙で吸引濾過して得られた濾液を用いた。
222.55質量部の水に5.25質量部のPEG(マクロゴール6000;日油社)及び272.2質量部の4.5%BT溶液を加え、ホモジナイザーで撹拌して得られたコーティング剤(以下、「実施例4コーティング剤」)を用いて、実施例1と同様の方法でフィルムを形成し、その水蒸気透過度及び酸素透過係数を測定した。また、実施例4コーティング剤のヘーズ値を測定した。
222.55質量部の水に5.25質量部のPEG(マクロゴール1000(平均分子量950~1050);日油社)及び272.2質量部の4.5%BT溶液を加え、ホモジナイザーで撹拌して得られたコーティング剤を用いて、実施例1と同様の方法でフィルムを形成し、その水蒸気透過度を測定した。
222.55質量部の水に5.25質量部のPEG(マクロゴール4000(平均分子量2600~3800;日油社)及び272.2質量部の4.5%BT溶液を加え、ホモジナイザーで撹拌して得られたコーティング剤を用いて、実施例1と同様の方法でフィルムを形成し、その水蒸気透過度を測定した。
222.55質量部の水に5.25質量部のPEG(マクロゴール20000(平均分子量20000~25000);日油社)及び272.2質量部の4.5%BT溶液を加え、ホモジナイザーで撹拌して得られコーティング剤を用いて、実施例1と同様の方法でフィルムを形成し、その水蒸気透過度を測定した。
333.94質量部の水に10.5質量部のPEG(マクロゴール6000;日油社)及び155.56質量部の4.5%BT溶液を加え、ホモジナイザーで撹拌して得られたコーティング剤を用いて、実施例1と同様の方法でフィルムを形成し、その水蒸気透過度を測定した。
59.0質量部の水に3.5質量部のPEG(マクロゴール6000;日油社)及び437.5質量部の3.2%BT溶液を加え、ホモジナイザーで撹拌して得られたコーティング剤を用いて、実施例1と同様の方法でフィルムを形成し、その水蒸気透過度を測定した。
156.38質量部の水に4.62質量部のPEG(マクロゴール6000;日油社)、336.9質量部の3.2%BT溶液及び2.1質量部のSpan80を加え、ホモジナイザーで撹拌して得られたコーティング剤を用いて、実施例1と同様の方法でフィルムを形成し、その水蒸気透過度を測定した。
156.38質量部の水に4.62質量部のPEG(マクロゴール6000;日油社)、336.9質量部の3.2%BT溶液及び2.1質量部のTween80(ポリソルベート 80)を加え、ホモジナイザーで撹拌して得られたコーティング剤を用いて、実施例1と同様の方法でフィルムを形成し、その水蒸気透過度を測定した。
112.0質量部の水に5.075質量部のPEG(マクロゴール6000;日油社)、382.8質量部の3.2%BT溶液及び0.175質量部の流動パラフィンを加え、ホモジナイザーで撹拌して得られたコーティング剤を用いて、実施例1と同様の方法でフィルムを形成し、その水蒸気透過度を測定した。
544.4質量部の4.5%BT溶液に10.5質量部のPEG(マクロゴール6000;日油社)を加えてホモジナイザーで撹拌し、3.5質量部のSpan20と531.15質量部の水を加えた後に450.45質量部のエタノールを加えて再びホモジナイザーで撹拌し、コーティング剤(以下、「実施例13コーティング剤」)を得た。
127.4質量部の4.5%BT溶液に2.46質量部のPEG(マクロゴール6000;日油社)を加えて撹拌し、0.81質量部のSpan20及び98.84質量部の水を加え、引き続き225.55質量部のエタノールを加え、ホモジナイザーで撹拌して得られたコーティング剤を用いて、実施例1と同様の方法でフィルムを形成し、その水蒸気透過度を測定した。
76.23質量部の4.5%BT溶液に1.47質量部のPEG(マクロゴール6000;日油社)を加えて撹拌し、2.10質量部のSpan20及び120.2質量部の水を加え、ホモジナイザーで撹拌して得られたコーティング剤を用いて、実施例1と同様の方法でフィルムを形成し、その水蒸気透過度を測定した。
1.12質量部のBT、0.47質量部のPEG6000、0.16質量部のSpan20及び28.2質量部の水を高速撹拌機(フィルミックス40-40型;プライミクス社)(以下、「フィルミックス」)に入れて5分間混合撹拌し、引き続き20.0質量部の水を加えスターラーで撹拌したものを濾紙で吸引濾過して得られたコーティング剤を用いて、実施例1と同様の方法でフィルムを形成し、その水蒸気透過度を測定した。
22.4質量部の5.0%BT溶液及び0.47質量部のPEG6000を5分間、フィルミックスを用いて混合撹拌し、0.16質量部のSpan20を加え、さらに5分間混合撹拌し、26.97質量部の水を加えスターラーで撹拌したものを濾紙で吸引濾過して得られたコーティング剤を用いて、実施例1と同様の方法でフィルムを形成し、その水蒸気透過度を測定した。なお、5.0%BT溶液としては、1.25質量部のBTと23.75質量部の水をフィルミックスで撹拌したものを用いた。
市販錠は平形状の裸錠であり、フィルムコーティングには不向きであるため、粉砕してR錠に再打錠した。市販のオルメサルタンメドキソミル含有錠剤(オルメテック錠(登録商標)20mg;第一三共社)を乳鉢で粉砕し、得られた粉砕物をロータリー打錠機で再度打錠してオルメサルタンメドキソミル核錠剤を得た(直径7mm、10R)。
上記の製法で得たオルメサルタンメドキソミル核錠剤をコーティングパン(DRC-200;パウレック社)に仕込み、フィルムの厚みが60~80μmになるまで実施例1のコーティン剤をオルメサルタンメドキソミル核錠剤に被覆した。こうして得られた被覆オルメサルタンメドキソミル錠及び市販のメトホルミン塩酸塩含有錠剤(グリコラン錠250mg(登録商標);日本新薬社)をそれぞれ同一ガラス瓶に入れてプラスチックキャップをし、40℃、相対湿度75%の条件下で1週間保存し、保存中にオルメサルタンメドキソミルから分解遊離するジアセチルによるメトホルミン塩酸塩含有錠剤の着色変化を色差計で評価した。
323.65質量部の水に12.25質量部のPEG(マクロゴール6000;日油社)及び164.1質量部の3.2%BT溶液を加え、ホモジナイザーで撹拌して得られたコーティング剤を用いて、実施例1と同様の方法でフィルムを形成し、その水蒸気透過度を測定した。
6.05質量部の水に1.75質量部のPEG(マクロゴール6000;日油社)及び492.2質量部の3.2%BT溶液を加え、ホモジナイザーで撹拌して得られたコーティング剤から、実施例1と同様の方法でフィルムを形成し、その水蒸気透過度を測定した。
111.95質量部の水に5.25質量部のポリエチレンオキサイド(PolyOX80;ダウコーニング社;以下、「PEO」)及び382.8質量部の3.2%BT溶液を加え、ホモジナイザーで撹拌して得られたコーティング剤を用いて、実施例1と同様の方法でフィルムを形成し、その水蒸気透過度を測定した。
特許文献4の実施例2に記載されたガスバリアコーティング剤を調製した。156.38質量部の水に4.62質量部のポリビニルアルコール(ゴーセノールEG05;日本合成化学社;以下、「PVA」)、336.9質量部の3.2%BT溶液及び2.1質量部のSpan20(ソルビタンモノラウレート)を加え、ホモジナイザーで撹拌してコーティング剤を得た(以下、「比較例4コーティング剤」)。
20gのモンテルカストナトリウム錠(シングレア錠(登録商標)10mg;萬有製薬)及び230gのプラセボ錠(嵩増し用)をコーティングパン(DRC-200;パウレック社)に仕込み、フィルムの厚みが50~60μmになるまで比較例4コーティング剤をモンテルカストナトリウム錠に被覆した。こうして得られた被覆モンテルカストナトリウム錠を40℃、相対湿度75%の条件下で1週間保存し、保存前後における溶出プロファイルを調べた。
33.81質量部の水に1.37質量部のポリエチレングリコール400(PEG400;日油社)及び100.0質量部の3.2%BT溶液を加え、ホモジナイザーで撹拌して得られたコーティング剤を用いて、実施例1と同様の方法でフィルムを形成し、その水蒸気透過度を測定した。
65.34質量部の4.5%BT溶液に1.26質量部のPEG(マクロゴール6000;日油社)を加えて撹拌し、2.80質量部のSpan20及び、130.6質量部の水を加え、ホモジナイザーで撹拌して得られたコーティング剤を用いて、実施例1と同様の方法でフィルムを形成し、その水蒸気透過度を測定した。
特許文献6の実施例2に記載されたガスバリアコーティング剤を調製した。15.0質量部のデキストロース(日本薬局方ブドウ糖NG-TDA;サンエイ糖化社)、35質量部のカルボキシメチルセルロースナトリウム(T.P.T-JP 50:五徳薬品社)を1200質量部の水に加えて撹拌溶解させ、コーティング剤を得た(以下「比較例8コーティング剤」)。
市販のバルプロ酸ナトリウム錠(デパケン錠(登録商標)200mg;協和発酵キリン社)について、40℃、相対湿度75%の条件下で12日間保存した後の外観観察し、さらに、その保存前後の溶出プロファイルをそれぞれ確認した。
市販のモンテルカストナトリウム錠(シングレア錠(登録商標)10mg;萬有製薬)について、40℃、相対湿度75%の条件下で1週間保存する前後の溶出プロファイルを確認した。
市販のモンテルカストナトリウム錠(シングレア錠(登録商標)10mg;萬有製薬)について、40℃、相対湿度75%の条件下で1週間保存する前後の吸湿増加量を算出した。
市販のオルメサルタンメドキソミル含有錠(オルメテック錠20mg:第一三共社)と市販のメトホルミン塩酸塩含有錠剤(グリコラン錠(登録商標)250mg:日本新薬)を同一ガラス瓶に入れてプラスチックキャップをし、40℃、相対湿度75%の条件下で1週間保存し、保存中にオルメサルタンメドキソミルから分解遊離するジアセチルによるメトホルミン塩酸塩含有錠剤の着色変化を色差計で評価した。
集束イオンビーム法を用い、実施例3及び実施例4でそれぞれ形成したフィルムの厚み方向の断面をTEMで観察した。実施例3で形成したフィルムについての顕微鏡像を図3に、実施例4で形成したフィルムについての顕微鏡像を図4に示す。
Claims (8)
- 平均分子量が950~25000のポリエチレングリコールと、膨潤性粘土とを含み、
前記ポリエチレングリコールと前記膨潤性粘土との質量比が2:8~6:4である、医薬固形製剤用のコーティング剤。 - 前記膨潤性粘土は、ベントナイト又はケイ酸マグネシウムアルミニウムである、請求項1記載のコーティング剤。
- 糖アルコール誘導体型界面活性剤を0.5~30%含有する、請求項1又は2記載のコーティング剤。
- 前記糖アルコール誘導体型界面活性剤は、ソルビタン脂肪酸エステルである、請求項3記載のコーティング剤。
- 請求項1~4のいずれか一項記載のコーティング剤から形成され、
室温40℃、相対湿度75%の条件下における水蒸気透過度が、1.0×10-4g・mm/cm2・24hr・atm未満である、医薬用フィルム製剤。 - 請求項1~4のいずれか一項記載のコーティング剤で被覆され、
室温40℃、相対湿度75%の条件下における水蒸気透過度が、1.0×10-4g・mm/cm2・24hr・atm未満である、被覆医薬固形製剤。 - 平均分子量が950~25000のポリエチレングリコールと、膨潤性粘土とを含み、
前記ポリエチレングリコールと前記膨潤性粘土との質量比が2:8~6:4であり、
室温40℃、相対湿度75%の条件下における水蒸気透過度が1.0×10-4g・mm/cm2・24hr・atm未満である、医薬用フィルム製剤。 - 平均分子量が950~25000のポリエチレングリコールと、膨潤性粘土とを含み、
前記ポリエチレングリコールと前記膨潤性粘土との質量比が2:8~6:4であり、
室温40℃、相対湿度75%の条件下における水蒸気透過度が1.0×10-4g・mm/cm2・24hr・atm未満である、被覆層、
を有する被覆医薬固形製剤。
Priority Applications (11)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201180042027.1A CN103079596B (zh) | 2010-08-31 | 2011-08-31 | 药物固体制剂用的包衣剂、药物用膜制剂以及包覆药物固体制剂 |
SI201131703T SI2612681T1 (sl) | 2010-08-31 | 2011-08-31 | Obložno sredstvo za farmacevtsko trdno obliko, farmacevtska filmska formulacija in obložena farmacevtska trdna oblika |
EP11821835.3A EP2612681B1 (en) | 2010-08-31 | 2011-08-31 | Coating agent for pharmaceutical solid preparation, pharmaceutical film formulation, and coated pharmaceutical solid preparation |
CA2803052A CA2803052C (en) | 2010-08-31 | 2011-08-31 | Coating agent for pharmaceutical solid preparation, pharmaceutical film formulation, and coated pharmaceutical solid preparation |
ES11821835T ES2715830T3 (es) | 2010-08-31 | 2011-08-31 | Agente de recubrimiento para una preparación sólida farmacéutica, formulación de película farmacéutica y preparación sólida farmacéutica recubierta |
MX2013002195A MX341726B (es) | 2010-08-31 | 2011-08-31 | Agente de revestimiento para preparacion solida farmaceutica, formulacion de pelicula farmaceutica, y preparacion solida farmaceutica revestida. |
BR112013000903A BR112013000903B1 (pt) | 2010-08-31 | 2011-08-31 | agente de revestimento para uma preparação sólida farmacêutica, formulação de filme farmacêutica, e, preparação sólida farmacêutica revestida |
PL11821835T PL2612681T3 (pl) | 2010-08-31 | 2011-08-31 | Środek powlekający do stałego preparatu farmaceutycznego, formulacja farmaceutyczna filmu i powlekany stały preparat farmaceutyczny |
KR1020137002285A KR101483476B1 (ko) | 2010-08-31 | 2011-08-31 | 의약 고형 제제용의 코팅제, 의약용 필름 제제 및 피복 의약 고형 제제 |
JP2011537088A JP5853699B2 (ja) | 2010-08-31 | 2011-08-31 | 医薬固形製剤用のコーティング剤、医薬用フィルム製剤及び被覆医薬固形製剤 |
US13/819,523 US9381248B2 (en) | 2010-08-31 | 2011-08-31 | Coating agent for pharmaceutical solid preparation, pharmaceutical film formulation, and coated pharmaceutical solid preparation |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2010194355 | 2010-08-31 | ||
JP2010-194355 | 2010-08-31 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2012029820A1 true WO2012029820A1 (ja) | 2012-03-08 |
Family
ID=45772899
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2011/069692 WO2012029820A1 (ja) | 2010-08-31 | 2011-08-31 | 医薬固形製剤用のコーティング剤、医薬用フィルム製剤及び被覆医薬固形製剤 |
Country Status (14)
Country | Link |
---|---|
US (1) | US9381248B2 (ja) |
EP (1) | EP2612681B1 (ja) |
JP (1) | JP5853699B2 (ja) |
KR (1) | KR101483476B1 (ja) |
CN (1) | CN103079596B (ja) |
BR (1) | BR112013000903B1 (ja) |
CA (1) | CA2803052C (ja) |
ES (1) | ES2715830T3 (ja) |
HU (1) | HUE041795T2 (ja) |
MX (1) | MX341726B (ja) |
PL (1) | PL2612681T3 (ja) |
SI (1) | SI2612681T1 (ja) |
TW (1) | TWI535463B (ja) |
WO (1) | WO2012029820A1 (ja) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014188728A1 (ja) * | 2013-05-24 | 2014-11-27 | 持田製薬株式会社 | フィルムコーティング用組成物 |
JP2014224099A (ja) * | 2013-04-15 | 2014-12-04 | 株式会社三和化学研究所 | オルメサルタンメドキソミルを含有する医薬組成物 |
WO2015152195A1 (ja) * | 2014-03-31 | 2015-10-08 | 東レ株式会社 | 固形製剤用のコーティング剤並びにこれから形成された被膜及び被覆固形製剤 |
JP2018201465A (ja) * | 2017-06-08 | 2018-12-27 | 株式会社三旺コーポレーション | 水素発生素材含有組成物及びその製造方法 |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2024049155A1 (ko) * | 2022-08-31 | 2024-03-07 | (주)셀트리온 | 이중 냄새 차폐 약학 조성물 |
Citations (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2000508673A (ja) * | 1996-04-20 | 2000-07-11 | ロシュ ダイアグノスティクス ゲゼルシャフト ミット ベシュレンクテル ハフツング | イバンドロネートを含む経口薬理製剤 |
JP2000273045A (ja) * | 1991-01-30 | 2000-10-03 | Wellcome Found Ltd:The | 水分散性錠剤 |
JP2003509339A (ja) * | 1999-07-09 | 2003-03-11 | バーウィンド・ファーマスーティカル・サーヴィスィーズ・インコーポレーテッド | フィルムコーティングおよびポリビニルアルコールをベースとするフィルムコーティング組成物 |
JP2004518750A (ja) | 2001-02-27 | 2004-06-24 | レーム ゲゼルシヤフト ミツト ベシユレンクテル ハフツング ウント コンパニー コマンディートゲゼルシャフト | 貯蔵安定性を改良するための、医薬品配合物用被覆材料および結合材料 |
WO2005019286A1 (ja) | 2003-08-20 | 2005-03-03 | Shionogi & Co., Ltd. | 新規コーティング組成物 |
JP2006188490A (ja) | 2004-12-06 | 2006-07-20 | Freunt Ind Co Ltd | フィルムコーティング組成物、その皮膜および錠剤 |
WO2006123765A1 (ja) | 2005-05-20 | 2006-11-23 | Daiichi Sankyo Company, Limited | フィルムコーティング製剤 |
WO2007145191A1 (ja) | 2006-06-13 | 2007-12-21 | Nippon Shinyaku Co., Ltd. | 被覆錠剤 |
WO2008041663A1 (en) | 2006-09-25 | 2008-04-10 | Takeda Pharmaceutical Company Limited | Medicinal package |
JP2009521518A (ja) * | 2005-12-26 | 2009-06-04 | ラボラトリオス、レスビ、ソシエダッド、リミターダ | 無水オランザピンi型の経口処方物 |
JP2009539896A (ja) * | 2006-06-16 | 2009-11-19 | エルテーエス ローマン テラピー−ジステーメ アーゲー | 2型糖尿病組み合わせウェーハ |
JP2009539897A (ja) * | 2006-06-16 | 2009-11-19 | エルテーエス ローマン テラピー−ジステーメ アーゲー | オピオイド組み合わせウェーハ |
JP2010513329A (ja) * | 2006-12-20 | 2010-04-30 | ミラン ファーマシューティカルズ ユーエルシー | ホットメルト顆粒化潤滑剤を含んでなる医薬組成物 |
WO2010074223A1 (ja) | 2008-12-25 | 2010-07-01 | 東レ株式会社 | 固形製剤用のコーティング剤及びこれを用いた固形製剤 |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2766209A (en) * | 1954-05-21 | 1956-10-09 | Pure Oil Co | Clay thickened lubricants having water resistant characteristics |
US3383237A (en) * | 1964-01-29 | 1968-05-14 | Richardson Merrell Inc | Tablet coating |
US4476271A (en) * | 1981-05-07 | 1984-10-09 | Dai Nippon Toryo Co., Ltd. | Aqueous dispersion type thermosetting coating composition |
US5639561A (en) * | 1994-09-15 | 1997-06-17 | Drescher Geschaeftsdrucke Gmbh | Single-layered paper product |
US20080305173A1 (en) | 2001-07-31 | 2008-12-11 | Beuford Arlie Bogue | Amorphous drug beads |
CA2503380A1 (en) | 2002-10-25 | 2004-05-06 | Dexcel Pharma Technologies Ltd. | Pharmaceutical compositions containing venlafaxine |
WO2009099734A1 (en) | 2008-02-05 | 2009-08-13 | Merck & Co., Inc. | Pharmaceutical compositions of a combination of metformin and a dipeptidyl peptidase-iv inhibitor |
KR20090128918A (ko) | 2008-06-11 | 2009-12-16 | 한국화학연구원 | 염산 알푸조신이 함유된 서방형 제제의 제조 |
GB201014041D0 (en) | 2010-08-23 | 2010-10-06 | Biofilm Ltd | Soluble film |
-
2011
- 2011-08-31 HU HUE11821835A patent/HUE041795T2/hu unknown
- 2011-08-31 TW TW100131188A patent/TWI535463B/zh active
- 2011-08-31 PL PL11821835T patent/PL2612681T3/pl unknown
- 2011-08-31 WO PCT/JP2011/069692 patent/WO2012029820A1/ja active Application Filing
- 2011-08-31 CA CA2803052A patent/CA2803052C/en active Active
- 2011-08-31 JP JP2011537088A patent/JP5853699B2/ja active Active
- 2011-08-31 EP EP11821835.3A patent/EP2612681B1/en active Active
- 2011-08-31 US US13/819,523 patent/US9381248B2/en active Active
- 2011-08-31 BR BR112013000903A patent/BR112013000903B1/pt active IP Right Grant
- 2011-08-31 MX MX2013002195A patent/MX341726B/es active IP Right Grant
- 2011-08-31 SI SI201131703T patent/SI2612681T1/sl unknown
- 2011-08-31 ES ES11821835T patent/ES2715830T3/es active Active
- 2011-08-31 KR KR1020137002285A patent/KR101483476B1/ko active IP Right Grant
- 2011-08-31 CN CN201180042027.1A patent/CN103079596B/zh active Active
Patent Citations (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2000273045A (ja) * | 1991-01-30 | 2000-10-03 | Wellcome Found Ltd:The | 水分散性錠剤 |
JP2000508673A (ja) * | 1996-04-20 | 2000-07-11 | ロシュ ダイアグノスティクス ゲゼルシャフト ミット ベシュレンクテル ハフツング | イバンドロネートを含む経口薬理製剤 |
JP2003509339A (ja) * | 1999-07-09 | 2003-03-11 | バーウィンド・ファーマスーティカル・サーヴィスィーズ・インコーポレーテッド | フィルムコーティングおよびポリビニルアルコールをベースとするフィルムコーティング組成物 |
JP2004518750A (ja) | 2001-02-27 | 2004-06-24 | レーム ゲゼルシヤフト ミツト ベシユレンクテル ハフツング ウント コンパニー コマンディートゲゼルシャフト | 貯蔵安定性を改良するための、医薬品配合物用被覆材料および結合材料 |
WO2005019286A1 (ja) | 2003-08-20 | 2005-03-03 | Shionogi & Co., Ltd. | 新規コーティング組成物 |
JP2006188490A (ja) | 2004-12-06 | 2006-07-20 | Freunt Ind Co Ltd | フィルムコーティング組成物、その皮膜および錠剤 |
WO2006123765A1 (ja) | 2005-05-20 | 2006-11-23 | Daiichi Sankyo Company, Limited | フィルムコーティング製剤 |
JP2009521518A (ja) * | 2005-12-26 | 2009-06-04 | ラボラトリオス、レスビ、ソシエダッド、リミターダ | 無水オランザピンi型の経口処方物 |
WO2007145191A1 (ja) | 2006-06-13 | 2007-12-21 | Nippon Shinyaku Co., Ltd. | 被覆錠剤 |
JP2009539896A (ja) * | 2006-06-16 | 2009-11-19 | エルテーエス ローマン テラピー−ジステーメ アーゲー | 2型糖尿病組み合わせウェーハ |
JP2009539897A (ja) * | 2006-06-16 | 2009-11-19 | エルテーエス ローマン テラピー−ジステーメ アーゲー | オピオイド組み合わせウェーハ |
WO2008041663A1 (en) | 2006-09-25 | 2008-04-10 | Takeda Pharmaceutical Company Limited | Medicinal package |
JP2010513329A (ja) * | 2006-12-20 | 2010-04-30 | ミラン ファーマシューティカルズ ユーエルシー | ホットメルト顆粒化潤滑剤を含んでなる医薬組成物 |
WO2010074223A1 (ja) | 2008-12-25 | 2010-07-01 | 東レ株式会社 | 固形製剤用のコーティング剤及びこれを用いた固形製剤 |
Non-Patent Citations (2)
Title |
---|
"Dissolution Test", article "The Japanese Pharmacopoeia" |
See also references of EP2612681A4 |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2014224099A (ja) * | 2013-04-15 | 2014-12-04 | 株式会社三和化学研究所 | オルメサルタンメドキソミルを含有する医薬組成物 |
WO2014188728A1 (ja) * | 2013-05-24 | 2014-11-27 | 持田製薬株式会社 | フィルムコーティング用組成物 |
JPWO2014188728A1 (ja) * | 2013-05-24 | 2017-02-23 | 持田製薬株式会社 | フィルムコーティング用組成物 |
WO2015152195A1 (ja) * | 2014-03-31 | 2015-10-08 | 東レ株式会社 | 固形製剤用のコーティング剤並びにこれから形成された被膜及び被覆固形製剤 |
KR20160137507A (ko) | 2014-03-31 | 2016-11-30 | 도레이 카부시키가이샤 | 고형 제제용의 코팅제 및 이것으로 형성된 피막 및 피복 고형 제제 |
JPWO2015152195A1 (ja) * | 2014-03-31 | 2017-04-13 | 東レ株式会社 | 固形製剤用のコーティング剤並びにこれから形成された被膜及び被覆固形製剤 |
US10022331B2 (en) | 2014-03-31 | 2018-07-17 | Toray Industries, Inc. | Coating agent for solid preparation, and film and coated solid preparation formed therewith |
JP2018201465A (ja) * | 2017-06-08 | 2018-12-27 | 株式会社三旺コーポレーション | 水素発生素材含有組成物及びその製造方法 |
Also Published As
Publication number | Publication date |
---|---|
EP2612681B1 (en) | 2019-01-30 |
US9381248B2 (en) | 2016-07-05 |
SI2612681T1 (sl) | 2019-05-31 |
CN103079596B (zh) | 2015-08-19 |
PL2612681T3 (pl) | 2019-09-30 |
JP5853699B2 (ja) | 2016-02-09 |
TWI535463B (zh) | 2016-06-01 |
CN103079596A (zh) | 2013-05-01 |
CA2803052A1 (en) | 2012-03-08 |
ES2715830T3 (es) | 2019-06-06 |
US20130156829A1 (en) | 2013-06-20 |
BR112013000903A2 (pt) | 2016-05-17 |
EP2612681A1 (en) | 2013-07-10 |
MX2013002195A (es) | 2013-03-18 |
BR112013000903B1 (pt) | 2019-12-03 |
JPWO2012029820A1 (ja) | 2013-10-31 |
CA2803052C (en) | 2014-10-28 |
EP2612681A4 (en) | 2014-04-30 |
KR101483476B1 (ko) | 2015-01-16 |
TW201212953A (en) | 2012-04-01 |
KR20130020966A (ko) | 2013-03-04 |
MX341726B (es) | 2016-08-31 |
HUE041795T2 (hu) | 2019-05-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
TWI438012B (zh) | 固態製劑用之塗覆劑及使用其之固態製劑 | |
KR101445671B1 (ko) | 피복 고형 제제 | |
TWI484976B (zh) | 固形製劑用薄膜塗布劑及用其之固形製劑 | |
JP5853699B2 (ja) | 医薬固形製剤用のコーティング剤、医薬用フィルム製剤及び被覆医薬固形製剤 | |
TWI446923B (zh) | 被覆固形製劑 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WWE | Wipo information: entry into national phase |
Ref document number: 2011537088 Country of ref document: JP Ref document number: 201180042027.1 Country of ref document: CN |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 11821835 Country of ref document: EP Kind code of ref document: A1 |
|
ENP | Entry into the national phase |
Ref document number: 2803052 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 4060/KOLNP/2012 Country of ref document: IN |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2011821835 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref document number: 20137002285 Country of ref document: KR Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: MX/A/2013/002195 Country of ref document: MX |
|
WWE | Wipo information: entry into national phase |
Ref document number: 13819523 Country of ref document: US |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
REG | Reference to national code |
Ref country code: BR Ref legal event code: B01A Ref document number: 112013000903 Country of ref document: BR |
|
ENP | Entry into the national phase |
Ref document number: 112013000903 Country of ref document: BR Kind code of ref document: A2 Effective date: 20130114 |