WO2010074223A1 - 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 - Google Patents
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 Download PDFInfo
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- WO2010074223A1 WO2010074223A1 PCT/JP2009/071573 JP2009071573W WO2010074223A1 WO 2010074223 A1 WO2010074223 A1 WO 2010074223A1 JP 2009071573 W JP2009071573 W JP 2009071573W WO 2010074223 A1 WO2010074223 A1 WO 2010074223A1
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- coating agent
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- 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
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- 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
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- 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
- A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
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- 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
- A61K9/282—Organic compounds, e.g. fats
- A61K9/2826—Sugars or sugar alcohols, e.g. sucrose; Derivatives thereof
-
- 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
- A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
Definitions
- the present invention relates to a coating agent for a solid preparation and a solid preparation using the same.
- Patent Document 1 a resin composition obtained by copolymerizing polyvinyl alcohol and a polymerizable vinyl monomer
- Patent Document 2 An improved coating agent
- Patent Document 3 a method of dispersing an intercalation compound in polyvinyl alcohol has been proposed (Patent Documents 3 to 4). 4).
- an object of the present invention is to provide a coating agent for a solid preparation that can stably maintain the quality of medicinal ingredients in the solid preparation for a long period of time so that a single-packed preparation can be made even in an unwrapped state.
- a coating agent in which a swellable clay has a specific laminated structure in a high hydrogen bonding resin has a gas barrier property (oxygen) equal to or higher than that of a PTP sheet.
- Permeability coefficient 1 ⁇ 10 ⁇ 4 cm 3 ⁇ mm / cm 2 ⁇ less than 24 hr ⁇ atm; water vapor permeability 1 ⁇ 10 ⁇ 4 g ⁇ mm / cm 2 ⁇ less than 24 hr ⁇ atm) I found it.
- the present invention provides a coating agent for a solid preparation containing a high hydrogen bonding resin and a swellable clay.
- this coating agent is coated (coated) on a solid preparation and dried, the layered structure of the above swellable clay forms a film in which the layered structure is dispersed in a network, so that the gas barrier property of the coating agent is reduced. It can be increased to the same level as or higher than that of the PTP packaging material. Further, since the formed film is thinner than the sugar coating, it does not adversely affect the patient's dose.
- the ratio of the area occupied by the laminated structure that is plane-oriented to the area of the longitudinal section of the film is preferably 30% or more, and the mass of the highly hydrogen-bonding resin and the swellable clay The ratio is more preferably 4: 6 to 6: 4.
- the swellable clay laminated structures tend to be entangled with each other, and the gas barrier property of the resulting film can be further enhanced.
- the coating agent preferably contains a sugar alcohol derivative type surfactant, and in this case, the mass ratio of the high hydrogen bond resin to the swellable clay is 2: 8 to 5: 5.
- the content of the sugar alcohol derivative surfactant is preferably 7 to 35%. If the coating agent contains a sugar alcohol derivative type surfactant, the oxygen permeability coefficient and water vapor permeability of the formed film can be lowered, and the stability of medicinal ingredients in solid preparations against oxygen and water vapor Can be further enhanced.
- the high hydrogen bonding resin is preferably polyvinyl alcohol, and the swellable clay is preferably bentonite.
- Polyvinyl alcohol enhances the oxygen barrier property under low humidity
- bentonite enhances the gas barrier property under high humidity by causing a labyrinth effect by surface orientation parallel to the surface direction of the high hydrogen bonding resin layer. Can do.
- the sugar alcohol derivative surfactant is preferably a sorbitan fatty acid ester. If the said coating agent contains sorbitan fatty acid ester, the dispersibility of swelling clay can be improved and the gas barrier property under high humidity can be improved.
- the present invention also provides a solid preparation coated with the above coating agent.
- This solid preparation can maintain the stability of the medicinal component in the solid preparation for a long period of time to such an extent that it can be packaged even without packaging.
- the solid preparation can be coated as a thin film that does not adversely affect the dosage, and a gas barrier property equal to or higher than that of a packaging material such as a PTP sheet can be imparted to the solid preparation.
- a gas barrier property equal to or higher than that of a packaging material such as a PTP sheet can be imparted to the solid preparation.
- the solid preparation coated with the above coating agent can maintain the stability of the medicinal ingredients in the solid preparation for a long period of time even in an unwrapped state, and can be used in a single-packed preparation without causing deterioration in the quality of the pharmaceutical product. it can.
- the coating agent of the present invention is excellent in moisture resistance but also in disintegration, it can be applied not only to a sustained-release preparation but also to a rapid-release preparation. Furthermore, since the coating agent of the present invention can be produced using a coating apparatus commonly used by those skilled in the art, for example, a continuous air-flow coating apparatus, a fluidized bed coating apparatus, a pan coater, etc., it is versatile and solid. The coating operation to the preparation can be easily performed.
- FIG. 2 is a focused ion beam transmission electron microscope image of the film of Example 1.
- FIG. 3 is a focused ion beam transmission electron microscope image of the film of Example 2.
- FIG. It is a focused ion beam transmission electron microscope image of the film of Example 3.
- 6 is a focused ion beam transmission electron microscope image of the film of Comparative Example 4.
- 10 is a focused ion beam transmission electron microscope image of the film of Comparative Example 5. It is the graph which showed transition of the drug residual rate of an ascorbic acid tablet. It is the graph which showed transition of the drug residual rate of a bromide propantelin tablet.
- the coating agent of the present invention is characterized by containing a highly hydrogen bonding resin and a swellable clay.
- the laminate structure of the swellable clay is plane-oriented, In order to form a film dispersed in a shape, the gas barrier property of the coating agent can be improved to be equal to or higher than that of the PTP packaging material.
- Coating agent is a composition used to prevent a medicinal component contained in a solid preparation from being decomposed by oxygen, water vapor, light, etc. by coating the solid preparation to form a thin film. It is.
- the coating agent can be prepared by dispersing in a suitable solvent according to the purpose of use, and can be used to coat a solid preparation or to produce a film or a film preparation.
- the film can be obtained by drying a solvent (such as moisture) from the coating agent or a solution containing the coating agent, and the film preparation can be obtained by adding a medicinal component to the coating agent and drying in the same manner. it can.
- the solvent examples include water, a chain formula (lower alcohol) having 1 to 5 carbon atoms, or a mixed solvent thereof, but water is particularly preferable.
- High hydrogen bonding resin refers to a resin having a high content of hydrogen bonding groups in the resin.
- the high hydrogen bonding resin has a high hydrogen bonding group mass ratio of 5 to 60% per unit mass of the resin.
- Hydrogen bonding resin is mentioned.
- the hydrogen bonding group include a hydroxyl group, an amino group, a thiol group, a carboxyl group, a sulfonic acid group, and a phosphoric acid group.
- the high hydrogen bonding resin used in the coating agent has a high hydroxyl group content. Resin is more suitable.
- polyvinyl alcohol and polysaccharide are mentioned, for example, Polyvinyl alcohol and sodium carboxymethylcellulose are preferable, and polyvinyl alcohol is more preferable. Polyvinyl alcohol may also include derivatives thereof. Note that the above high hydrogen bonding resins may be used in combination as long as the gas barrier properties are not lowered.
- the above-mentioned polyvinyl alcohol generally means a product obtained by saponifying polyvinyl acetate, and is a completely saponified product in which only several percent of acetate groups remain from partially saponified polyvinyl alcohol in which several tens percent of acetate groups remain.
- the saponification degree of polyvinyl alcohol is preferably 70 to 97 mol%.
- the average degree of polymerization is preferably 200 to 3000, and more preferably 600 to 2400. In addition, you may mix and use 2 or more types of polyvinyl alcohol from which saponification degree and average polymerization degree differ in said polyvinyl alcohol.
- polyvinyl alcohol for example, there is a method of adding a low polymerization grade and subsequently mixing a high polymerization grade.
- polyvinyl alcohol include various types of poval (Kuraray Co., Ltd.) and gohsenol (Nippon Synthetic Chemical Industry).
- “Swellable clay” is a clay having swelling properties, but more specifically, among finely divided substances that exhibit viscosity and plasticity when they contain an appropriate amount of water, they have swelling properties. Refers to the substance.
- the swellable clay is preferably negatively charged due to the composition balance of the metal salt species, and examples thereof include smectites such as hydrous aluminum silicate having a three-layer structure.
- the negative charge is a state where the swellable clay has a cation exchange property, and the charge amount is expressed as a cation exchange capacity (CEC).
- CEC cation exchange capacity
- the unit of cation exchange capacity is milligram equivalent / 100 gram (usually expressed as meq / 100 g), and is generally expressed as the number of equivalents corresponding to the molar concentration of monovalent ions.
- Smectite includes beidellite, nontronite, saponite, hectorite, soconite, bentonite, magnesium aluminum silicate, and the like, which can be used alone or in combination of two or more.
- smectites magnesium aluminum silicate and bentonite are preferable, and bentonite is more preferable.
- the above swellable clays may be used in combination as long as the gas barrier properties are not lowered.
- Solid preparation means a solid preparation, for example, tablets (including sublingual tablets and orally disintegrating tablets), capsules (including soft capsules and microcapsules), granules, fine granules, and powders. Pills, troches, films and the like.
- Examples of the method for coating a solid preparation include a coating method using a coating pan, a tablet coating machine, etc. if it is in the form of a tablet, and a fluidized bed coating machine, rolling, if it is in the form of granules or powder.
- the coating method using a fluidized bed coating machine etc. is mentioned.
- “Laminated structure” refers to a laminated structure formed by stacking a plurality of layered structures
- plane orientation refers to arrangement parallel to a reference plane. That is, “a film in which a layered structure of swellable clay is oriented in a plane and dispersed in a network” means that 10 to 100 layers of swellable clay strips are stacked to form a layered structure. This refers to a film in which the body is arranged substantially parallel to the cross section of the film (cross section parallel to the film surface), and each strip is dispersed in a mesh shape in the film. In this case, the strips are not only oriented in parallel, but may be oriented with waviness, or may be oriented while approaching or leaving the strip running in the front, rear, left and right directions.
- the gas barrier property (oxygen permeability coefficient: 1 ⁇ ) is equal to or higher than that of a packaging material such as a PTP sheet. 10 ⁇ 4 cm 3 ⁇ mm / cm 2 ⁇ 24 hr ⁇ atm; water vapor permeability: less than 1 ⁇ 10 ⁇ 4 g ⁇ mm / cm 2 ⁇ 24 hr ⁇ atm) can be imparted to the solid preparation.
- the ratio of the area occupied by the plane-oriented laminated structure to the area of the longitudinal section (cross section perpendicular to the coating surface) of the coating is 30% or more, 35 % Or more is more preferable, and it is further more preferable that it is 42% or more.
- the coating agent preferably has a mass ratio of the high hydrogen bonding resin and the swellable clay of 4: 6 to 6: 4.
- the mass ratio of the high hydrogen bonding resin and the swellable clay is 3: 7 or less, the viscosity of the coating agent becomes high and spraying may be difficult. In this case, spraying may be possible by lowering the concentration of the coating agent, but other problems such as an increase in manufacturing time may occur.
- the mass ratio of the high hydrogen bonding resin and the swellable clay is 7: 3 or more, gas barrier properties equivalent to or higher than those of packaging materials such as PTP sheets may not be obtained.
- a sugar alcohol derivative-type surfactant refers to a surfactant having a sugar alcohol skeleton in the molecule.
- examples of the sugar alcohol include mannitol, xylitol, maltitol, trehalose, inositol, sorbitol and the like.
- sugar alcohol having a structure in which a hydrophobic group is ester-bonded examples include sorbitan fatty acid ester, polyoxyalkylene sorbitan fatty acid ester, sucrose fatty acid ester, sorbit fatty acid ester, polyoxyalkylene sorbit fatty acid ester, polyglycerin, polyglycerin fatty acid ester Glycerin fatty acid ester, polyoxyalkylene glycerin fatty acid ester and the like.
- sorbitan fatty acid ester and sucrose fatty acid ester are preferable, and sorbitan fatty acid ester is more preferable.
- sorbitan fatty acid esters those having a high monoester ratio are preferred, and those having an HLB (Hydrophilic Lyophilic Balance) in the range of 4 to 10 are preferred.
- HLB Hydrophilic Lyophilic Balance
- the acyl group constituting the hydrophobic group may be any of saturated, unsaturated, straight chain and branched chain, but preferably has 12 to 18 carbon atoms.
- sorbitan fatty acid esters examples include sorbitan monolaurate, sorbitan monopalmitate, and sorbitan monooleate, which can be suitably used for the coating agent.
- the above sugar alcohol derivative surfactants may be used in combination as long as the gas barrier properties are not lowered.
- the mass ratio of the high hydrogen bonding resin to the swellable clay is preferably 2: 8 to 5: 5, more preferably 2: 8 to 4: 6. 2: 8 to 3: 7 are more preferable.
- the mass ratio of the high hydrogen bonding resin and the swellable clay is 1: 9 or less, the viscosity of the coating becomes high and the coating operation becomes difficult. In this case, it may be possible to coat by lowering the concentration of the coating agent by adding a solvent, but another problem such as an increase in manufacturing time arises.
- the mass ratio of the high hydrogen bonding resin and the swellable clay is 6: 4 or more, a gas barrier property equal to or higher than that of a packaging material such as a PTP sheet may not be obtained.
- the content of the sugar alcohol derivative-type surfactant varies depending on the ratio of the high hydrogen bonding resin and the swellable clay, but is preferably 7 to 35%, more preferably 10 to 30%. Preferably, it is 12 to 24%.
- “content ratio of sugar alcohol derivative-type surfactant” means a sugar alcohol derivative-type surfactant with respect to the entire mixture obtained by adding a sugar alcohol derivative-type surfactant to a high hydrogen bonding resin and a swellable clay. The ratio (%) is shown.
- the coating on the solid preparation is facilitated, and the gas barrier property of the obtained film is improved, but depending on the mass ratio of the highly hydrogen bonding resin and the swellable clay,
- the content of the sugar alcohol derivative-type surfactant is 6% or less or 36% or more, a gas barrier property equivalent to or higher than that of a packaging material such as a PTP sheet may not be obtained.
- a pharmaceutically acceptable additive may be added to the coating agent as long as the gas barrier property is not lowered.
- the disintegration of the film can be improved, and when triethyl citrate, polyethylene glycol or glycerin is added as a plasticizer, the strength of the film can be improved.
- an additive usually used by those skilled in the art for film coating may be further added to the coating agent.
- additives include colorants such as plant extract pigments and shielding agents such as titanium oxide, calcium carbonate, and silicon dioxide.
- the solid preparation of the present invention is characterized by being coated with the above coating agent.
- solid preparation examples include tablets (including sublingual tablets and orally disintegrating tablets), capsules (including soft capsules and microcapsules), granules, fine granules, powders, pills, troches, and film agents. Is mentioned.
- the solid preparation may have a coating film on the surface of a solid preparation having another film made of a gastric or enteric polymer substance, and the solid preparation has a coating film. It may have another film made of a gastric or enteric polymer substance on its surface.
- the dispersion state, oxygen permeability coefficient, and water vapor permeability of the swellable clay were measured using a film (film) obtained from the coating agent.
- the film was thinned with a gadolinium ion beam using the focused ion beam method (FB-2000A; High-Tech Manufacturing & Service Co., Ltd.). The thinned film was observed with a transmission electron microscope (H-9000UHR; Hitachi High-Tech Manufacturing & Service Co., Ltd.), and the number of swellable clays was visually measured.
- FB-2000A focused ion beam method
- H-9000UHR Hitachi High-Tech Manufacturing & Service Co., Ltd.
- the swellable clay When the swellable clay is plane-oriented with respect to the cross section of the film (cross section parallel to the film surface), a well-defined and clear microscopic image is obtained, and a single layer of swellable clay (thickness of about 1 nm) ) And its laminated structure can be observed. On the other hand, when it is not plane-oriented, it becomes a blurred microscope image that is out of focus. For this reason, the ratio of the layered structure of the swellable clay that is plane-oriented with respect to the cross section of the film is the same as the observation area (2.5 ⁇ m ⁇ 2.5 ⁇ m square). ) Divided by the area. The area was digitized by image analysis using NIHimage.
- the oxygen permeability coefficient was measured based on the gas permeability test method by the gas chromatograph method JIS K7126-1 (2006), which is a standard in the technical field, and the oxygen permeability coefficient measuring devices (GTR-30XAD2 and G2700T ⁇ F; GTR Tech). ) At a temperature of 23 ⁇ 2 ° C. under conditions of 0% relative humidity (0% RH) and 90% relative humidity (90% RH). Hereinafter, the relative humidity is abbreviated as RH.
- Reference Example 2 Preparation of Modified PVA-Based Film 45.0 parts by mass of water, 3.5 parts by mass of POVACOAT (registered trademark) (Nisshin Kasei Co., Ltd.), 1.0 parts by mass of titanium oxide, 0.5 parts by mass Part of talc was added and stirred and mixed to obtain a dispersion, and a film was obtained in the same manner as in Reference Example 1.
- This film is a modified PVA-based film.
- Reference Example 3 Preparation of Sodium Carboxymethyl Cellulose Film 46.5 parts by weight of water and 3.5 parts by weight of OPAGLOS2 (registered trademark) (Nihon Colorcon) were mixed with stirring to obtain a dispersion.
- Reference Example A film was obtained in the same manner as in Example 1. This film is a sodium carboxymethylcellulose (CMC) film.
- CMC sodium carboxymethylcellulose
- Table 1 shows the results of measuring the oxygen permeability coefficient and water vapor permeability of the films of Reference Examples 1 to 3 used for coating the solid preparation.
- Example 1 To 42.55 parts by mass of water, 1.2 parts by mass of PVA (EG-05; Nippon Synthetic Chemical Co., Ltd.) and 56.25 parts by mass of a 3.2% bentonite solution are added and stirred with a homogenizer (Polytron Model KR). To obtain a dispersion. For the 3.2% bentonite solution, 32 parts by weight of bentonite (Kunipia-F; Kunimine Industries) (cation exchange capacity: 115 meq / 100 g) was added to 968 parts by weight of stirred water, and the mixture was uniformly dispersed with a homogenizer. What was suction-filtered with was used.
- bentonite is abbreviated as BT.
- the dispersion was sprayed on the back of the polypropylene balance tray and immediately dried with warm air from a dryer. After spray spraying and dryer drying were repeated several times, the balance tray was left in an oven at 50 ° C. and dried overnight. Then, the film was peeled from the balance tray to obtain the film of Example 1.
- Example 2 In 137.0 parts by mass of water, 2.64 parts by mass of PVA (EG-05; Nippon Synthetic Chemical Co., Ltd.), 192.5 parts by mass of 3.2% BT solution and 1.2 parts by mass of sorbitan monolaurate ( (Span 20; Wako Pure Chemical Industries, Ltd.) was added and stirred with a homogenizer (Polytron Model KR) to obtain a dispersion. From this dispersion, the film of Example 2 was obtained by the method of Example 1.
- PVA EG-05; Nippon Synthetic Chemical Co., Ltd.
- sorbitan monolaurate (Span 20; Wako Pure Chemical Industries, Ltd.) was added and stirred with a homogenizer (Polytron Model KR) to obtain a dispersion. From this dispersion, the film of Example 2 was obtained by the method of Example 1.
- Comparative Example 1 To 42.55 parts by mass of water, 1.2 parts by mass of hydroxypropylmethylcellulose (TC-5W; Shin-Etsu Chemical Co., Ltd.) and 56.25 parts by mass of 3.2% BT solution are added, and a homogenizer (Polytron Model KR) is used. Stir to obtain a dispersion. From this dispersion, the film of Comparative Example 1 was obtained by the method of Example 1.
- hydroxypropylmethylcellulose is abbreviated as HPMC.
- Comparative Example 2 10.0 parts by mass of PVA was added to 96.4 parts by mass of water, and the mixture was stirred with a stirrer to obtain a dispersion. From this dispersion, the film of Comparative Example 2 was obtained by the method of Example 1.
- Comparative Example 3 2.64 parts by mass of PVA, 6.16 parts by mass of talc and 1.2 parts by mass of sorbitan monolaurate were added to 56.7 parts by mass of water, and the mixture was stirred with a homogenizer to obtain a dispersion. From this dispersion, a film of Comparative Example 3 was obtained by the method of Example 1.
- Table 2 shows the results of measuring the oxygen permeability coefficient and water vapor permeability of the films obtained in Examples 1 and 2 and Comparative Examples 1 to 3.
- the film containing PVA and BT at a constant ratio in Examples 1 and 2 and the film containing PVA, BT and sorbitan monolaurate at a constant ratio are either of oxygen permeability coefficient or water vapor permeability.
- the gas barrier property was equal to or higher than that of the PTP packaging material.
- Example 1 Transmission electron microscope measurement of film
- FIG. 1 A microscopic image of Example 1 is shown in FIG. 1, and a microscopic image of Example 2 is shown in FIG.
- Example 3 To 51.6 parts by mass of water, 1.5 parts by mass of PVA and 46.9 parts by mass of 3.2% BT solution were added, and the film of Example 3 was obtained by the method of Example 1. Using the focused ion beam method, the cross section of the film of Example 3 was observed with a transmission electron microscope. A microscopic image is shown in FIG.
- Comparative Example 4 To 33.5 parts by mass of water, 0.9 part by mass of PVA and 65.6 parts by mass of 3.2% BT solution were added, and the film of Comparative Example 4 was obtained by the method of Example 1, and Example 3 The cross section of the film was observed by this method.
- FIG. 4 shows a microscopic image.
- Comparative Example 5 To 29.9 parts by mass of water, 2.25 parts by mass of PVA and 7.8 parts by mass of 3.2% BT solution were added, and the film of Comparative Example 5 was obtained by the method of Example 1, and Example 3 was obtained. The cross section of the film was observed by this method.
- FIG. 5 shows a microscopic image.
- Table 3 shows the BT dispersion state, oxygen permeability coefficient and water vapor permeability of the coatings obtained in Examples 1 to 3 and Comparative Examples 4 and 5.
- Example 4 In the configuration shown in Table 4, water, PVA and BT solution were mixed, and a film was obtained by the method of Example 1, and the oxygen permeability coefficient (23 ° C./90% RH) and water vapor permeability (40 ° C./75%) were obtained. RH) was measured.
- Example 6 Comparative Example 6
- water, PVA and BT solution were mixed, and a dispersion was obtained by the method of Example 1.
- a film was obtained by the method of Example 1, and the oxygen transmission coefficient (23 ° C./90% RH) and the water vapor transmission rate (40 ° C./75% RH) were measured.
- Table 4 shows the influence of the mass ratio of PVA and BT (PVA / BT) on the oxygen permeability coefficient and water vapor permeability.
- Examples 5 to 7 and Comparative Examples 7 to 9 Water, PVA, BT solution and each surfactant were mixed and a dispersion was obtained by the method of Example 2. A film was obtained by the method of Example 1, and the oxygen transmission coefficient (23 ° C./90% RH) and the water vapor transmission rate (40 ° C./75% RH) were measured.
- Table 5 shows the effect of the surfactant type on the oxygen permeability coefficient and water vapor permeability.
- the mass ratio of PVA, BT and surfactant was evaluated by fixing at 26.4: 61.6: 12 (26.4 / 61.6 / 12).
- Example 8 In the configuration shown in Table 6, water, PVA, BT solution, and sorbitan monolaurate were mixed, and a dispersion was obtained by the method of Example 1. A film was obtained by the method of Example 1, and the oxygen transmission coefficient (23 ° C./90% RH) and the water vapor transmission rate (40 ° C./75% RH) were measured.
- Table 6 shows the influence of the mass ratio of PVA and BT (PVA / BT) on the oxygen permeability coefficient and water vapor permeability.
- the content of sorbitan monolaurate was 12% in all cases.
- Example 11 and 12 and Comparative Example 12 In the configuration shown in Table 7, water, PVA, BT solution and sorbitan monolaurate were mixed and a dispersion was obtained by the method of Example 2. A film was obtained by the method of Example 1, and the oxygen transmission coefficient (23 ° C./90% RH) and the water vapor transmission rate (40 ° C./75% RH) were measured.
- Table 7 shows the influence of the content of sorbitan monolaurate on the oxygen permeability coefficient and water vapor permeability.
- the mass ratio (PVA / BT) of PVA and BT was fixed to 5: 5 (5/5) and evaluated.
- Example 13 and 14 and Comparative Examples 13 and 14 In the configuration shown in Table 8, water, PVA, BT solution and sorbitan monolaurate were mixed, and a dispersion was obtained by the method of Example 2. A film was obtained by the method of Example 1, and the oxygen transmission coefficient (23 ° C./90% RH) and the water vapor transmission rate (40 ° C./75% RH) were measured.
- Table 8 shows the influence of the content of sorbitan monolaurate on the oxygen permeability coefficient and water vapor permeability.
- the mass ratio (PVA / BT) of PVA and BT was fixed to 2: 8 (2/8) and evaluated.
- Example 15 (Production of coated tablet containing ascorbic acid coated with the dispersion of Example 2) 400 g of the ascorbic acid tablet of Comparative Example 15 was charged into a coating pan (Hi-Coater mini; Freund Sangyo), and the dispersion prepared in Example 2 was coated on the ascorbic acid-containing tablet as a coating agent. The coating agent was coated until the coating thickness became 60 ⁇ m to obtain an ascorbic acid-containing coated tablet. The ascorbic acid-containing coated tablet coated with the dispersion liquid of Example 2 thus obtained was designated as Example 15.
- Comparative Example 16 (Production of coated tablet containing ascorbic acid coated with the dispersion of Reference Example 3) 400 g of the ascorbic acid-containing tablet of Comparative Example 15 was charged into a coating pan (Hi-Coater mini; Freund Sangyo), and the dispersion prepared in Reference Example 3 was coated on the tablet as a coating agent. The coating agent was coated until the coating thickness was 60 ⁇ m. The ascorbic acid-containing coated tablet coated with the dispersion liquid of Reference Example 3 thus obtained was used as Comparative Example 16.
- the disintegration property of the ascorbic acid-containing coated tablet of Example 15 was evaluated using a dissolution tester. That is, one ascorbic acid-containing coated tablet was put into 900 mL of water heated to 37 ° C., and the time required for the film to start peeling from the tablet surface was measured. As a result, the time required for the film to start peeling from the tablet surface was about 2 minutes. As a result, the ascorbic acid-containing coated tablet of Example 15 was found to be excellent in disintegration, and the dispersion of Example 2 was used not only for sustained release preparations but also for coating rapid release preparations. It was suggested that it can be applied.
- the ascorbic acid-containing tablet of Comparative Example 15 and the ascorbic acid-containing coated tablet of Example 15 and Comparative Example 16 were stored in a desiccator at 25 ° C. and 95% RH for 4 weeks under an open condition or an airtight condition.
- the residual rate of ascorbic acid was evaluated.
- the open condition means that each tablet is left as it is in the desiccator
- the airtight condition means that each tablet is sealed in a glass bottle having a plastic inner lid and an outer lid, and is sealed. This means that it is left in the desiccator while holding
- FIG. 6 is a graph showing the transition of the drug residual rate.
- the white triangle ( ⁇ ) in FIG. 6 is the ascorbic acid-containing coated tablet of Example 15 that was allowed to stand under airtight conditions, and the black triangle ( ⁇ ) is the ascorbic acid-containing coated tablet of Example 15 that was allowed to stand under open conditions.
- White squares ( ⁇ ) are ascorbic acid-containing coated tablets of Comparative Example 16 left standing under airtight conditions
- black squares ( ⁇ ) are ascorbic acid-containing coated tablets of Comparative Example 16 left open under open conditions
- open circles ( ⁇ ) Indicates the result of the ascorbic acid-containing tablet of Comparative Example 15 left standing under confidential conditions
- the black circle ( ⁇ ) shows the result of the ascorbic acid-containing tablet of Comparative Example 15 left still under open conditions.
- the vertical axis represents the drug residual rate (%)
- the horizontal axis represents the storage period (W)
- W represents a week.
- the ascorbic acid-containing tablet of Comparative Example 15 and the ascorbic acid-containing coated tablet of Comparative Example 16 showed a decrease in the drug residual rate over time under the open conditions, whereas the ascorbic acid-containing coated tablet of Example 15 was released under the open conditions. Below, no degradation of the drug was observed even after storage for 4 weeks, and the same stability as when left standing under airtight conditions was maintained. As a result, the ascorbic acid-containing coated tablet of Example 15 was found to have a high barrier property against oxygen and water vapor.
- Example 16 (Production of coated tablet containing propanterin bromide coated with the dispersion of Example 2) 400 g of Propanthelin bromide-containing tablets of Comparative Example 17 were charged into a coating pan (Hi-Coater mini; Freund Sangyo), and the dispersion prepared in Example 2 was coated on the tablets containing Propanthelin bromide as a coating agent. The coating was coated with a coating agent until the coating thickness reached 60 ⁇ m to obtain a coated tablet containing propanterin bromide. The thus obtained coated tablet containing propantheline bromide was designated as Example 16.
- Comparative Example 18 (Production of coated tablets containing bromide propanterin coated with commercially available general-purpose coating formulations) A mixture of hydroxypropylmethylcellulose 2910, titanium oxide and macrogol 400 (Opadry OY-7300 (registered trademark); Nippon Colorcon) was added to distilled water and dissolved to obtain a commercially available general-purpose coating formulation liquid. 400 g of propantheline bromide-containing tablets of Comparative Example 17 were charged into a coating pan (Hi-Coater mini; Freund Sangyo), and a commercially available general-purpose coating formulation solution was coated on the tablets as a coating agent. The coating agent was coated until the coating thickness was 60 ⁇ m. The thus obtained brominated propantheline-containing coated tablet was used as Comparative Example 18.
- FIG. 7 is a graph showing the transition of the residual ratio (drug residual ratio) of propantheline bromide.
- white circles ( ⁇ ) are coated tablets containing bromide propanterin of Example 16
- black circles ( ⁇ ) are tablets containing propanterin bromide of Comparative Example 17
- black squares ( ⁇ ) are propane bromide of Comparative Example 18.
- Terrin-containing coated tablets, black triangles ( ⁇ ) show the results of the brominated propanterin-containing coated tablets of Comparative Example 19
- white triangles ( ⁇ ) show the results of the brominated propanterin sugar-coated tablets of Comparative Example 20.
- the vertical axis represents the drug residual rate (%)
- the horizontal axis represents the storage period (W)
- W represents a week.
- the gas barrier coating agent of the present invention is useful as a general-purpose coating agent for solid preparations, and particularly useful as a film for solid preparations containing drugs unstable to oxygen and water vapor. It was shown that.
- the coating agent of the present invention is useful as a coating agent for solid preparations, and particularly useful as a film for solid preparations containing drugs unstable to oxygen and water vapor.
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Abstract
Description
い。
集束イオンビーム法を用い、ガドリニウムイオンビームにより皮膜を薄膜化した(FB-2000A;ハイテクマニファクチャ&サービス社)。薄膜化した皮膜を透過型電子顕微鏡(H-9000UHR;日立ハイテクマニファクチャ&サービス社)で観察し、膨潤性粘土の積層数を目視で測定した。
酸素透過係数の測定は、当該技術分野の標準規格であるJIS K7126-1(2006)ガスクロマトグラフ法によるガス透過度試験方法に基づき、酸素透過係数測定装置(GTR―30XAD2及びG2700T・F;GTRテック社)を使用して、23±2℃の温度で、0%相対湿度(0%RH)と90%相対湿度(90%RH)の条件で測定した。以下、相対湿度をRHと略す。
水蒸気透過度の測定は、当該技術分野の標準規格であるJIS K8123(1994)を一部改変して試験した。まず、以下に記載した方法で調製した皮膜を光に透かし、ピンホールのない均一な厚さの部分を直径が3.5cmとなるように円形に切り取り、任意の5箇所で皮膜の厚みを測定した。次に、3gの塩化カルシウム(850~2000μmの粒度)をアルミニウムカップ(直径30mm)に入れ、アルミニウムカップの上に円形に切り取った皮膜と皮膜固定用のリングを順に乗せ、リングの上におもりを乗せてリングを固定し、その状態で溶融したパラフィンワックスをアルミニウムカップの縁に流し込んだ。パラフィンワックスが固化した後、おもりを取り除き、アルミニウムカップ全体の質量を量り、開始時質量とした。その後、アルミニウムカップを40℃、75%RHの恒温槽に入れ、24時間毎に取り出して質量を測定し、以下の式を用いて水蒸気透過係数を算出した。ただし、以下に記載した水蒸気透過度の測定試験においては、いずれもr=1.5cm、t=24時間、C=1atmであった。
W:24時間で増加した質量(g)
A:5箇所の皮膜の厚みの平均値(mm)
B:透過面積πr2(cm2)
t:経過時間(時間)
C:気圧(atm)
42.5質量部の水、7.5質量部のOPADRY II HP(商標登録)(日本カラコン社)を加えて攪拌混合し、分散液を得た。その後、この分散液を底面が平坦なポリプロピレン製トレイに注ぎ、水平を保った状態で50℃のオーブンで終夜乾燥させ、皮膜を得た。この皮膜は、ポリビニルアルコール(PVA)系皮膜である。以下、ポリビニルアルコールをPVAと略す。
45.0質量部の水、3.5質量部のPOVACOAT(商標登録)(日新化成社)、1.0質量部の酸化チタン、0.5質量部のタルクを加えて攪拌混合して分散液を得、参考例1と同様の方法で皮膜を得た。この皮膜は、変性PVA系皮膜である。
46.5質量部の水、3.5質量部のOPAGLOS2(商標登録)(日本カラコン社)を加えて攪拌混合して分散液を得、参考例1と同様の方法で皮膜を得た。この皮膜は、カルボキシメチルセルロースナトリウム(CMC)系の皮膜である。以下、カルボキシメチルセルロースナトリウムをCMCと略す。
42.55質量部の水に、1.2質量部のPVA(EG-05;日本合成化学社)、56.25質量部の3.2%ベントナイト溶液を加え、ホモジナイザー(ポリトロン Model KR)で攪拌し、分散液を得た。3.2%ベントナイト溶液は、攪拌した968質量部の水に32質量部のベントナイト(クニピア‐F;クニミネ工業)(カチオン交換能:115meq/100g)を添加し、ホモジナイザーにて均一分散させ、濾紙で吸引濾過したものを用いた。以下、ベントナイトをBTと略す。
137.0質量部の水に2.64質量部のPVA(EG-05;日本合成化学社)、192.5質量部の3.2%BT溶液及び1.2質量部のソルビタンモノラウレート(Span20;和光純薬社)を加え、ホモジナイザー(ポリトロン Model KR)で攪拌し、分散液を得た。この分散液から、実施例1の方法で実施例2の皮膜を得た。
42.55質量部の水に、1.2質量部のヒドロキシプロピルメチルセルロース(TC-5W;信越化学工業)、56.25質量部の3.2%BT溶液を加え、ホモジナイザー(ポリトロン Model KR)で攪拌し、分散液を得た。この分散液から、実施例1の方法で比較例1の皮膜を得た。以下、ヒドロキシプロピルメチルセルロースをHPMCと略す。
96.4質量部の水に、10.0質量部のPVAを加え、攪拌機で攪拌して分散液を得た。この分散液から、実施例1の方法で比較例2の皮膜を得た。
56.7質量部の水に、2.64質量部のPVA、6.16質量部のタルク及び1.2質量部のソルビタンモノラウレートを加え、ホモジナイザーで攪拌して分散液を得た。この分散液から、実施例1の方法で比較例3の皮膜を得た。
集束イオンビーム法を用い、実施例1及び2の皮膜の縦断面を透過型電子顕微鏡で観察した。実施例1の顕微鏡像を図1に、実施例2の顕微鏡像を図2に示す。
51.6質量部の水に、1.5質量部のPVA、46.9質量部の3.2%BT溶液を加え、実施例1の方法で実施例3の皮膜を得た。集束イオンビーム法を用い、実施例3の皮膜の断面を、透過型電子顕微鏡で観察した。顕微鏡像を図3に示す。
33.5質量部の水に、0.9質量部のPVA、65.6質量部の3.2%BT溶液を加え、実施例1の方法で比較例4の皮膜を得て、実施例3の方法で皮膜の断面を観察した。図4に顕微鏡像を示す。
89.9質量部の水に、2.25質量部のPVA、7.8質量部の3.2%BT溶液を加え、実施例1の方法で比較例5の皮膜を得て、実施例3の方法で皮膜の断面を観察した。図5に顕微鏡像を示す。
表4に示した構成で、水、PVA及びBT溶液を混合し、実施例1の方法で皮膜を得て、酸素透過係数(23℃・90%RH)及び水蒸気透過度(40℃・75%RH)を測定した。
表4に示した構成で、水、PVA及びBT溶液を混合し、実施例1の方法で分散液を得た。実施例1の方法で皮膜を得て、酸素透過係数(23℃・90%RH)及び水蒸気透過度(40℃・75%RH)を測定した。
水、PVA、BT溶液及び各界面活性剤を混合し、実施例2の方法で分散液を得た。実施例1の方法で皮膜を得て、酸素透過係数(23℃・90%RH)及び水蒸気透過度(40℃・75%RH)を測定した。
表6に示した構成で、水、PVA、BT溶液及びソルビタンモノラウレートを混合し、実施例1の方法で分散液を得た。実施例1の方法で皮膜を得て、酸素透過係数(23℃・90%RH)及び水蒸気透過度(40℃・75%RH)を測定した。
表6に示した構成で、水、PVA、BT溶液及びソルビタンモノラウレートを混合し、実施例2の方法で分散液を得た。実施例1の方法で皮膜を得て、酸素透過係数(23℃・90%RH)及び水蒸気透過度(40℃・75%RH)を測定した。
表7に示した構成で、水、PVA、BT溶液及びソルビタンモノラウレートを混合し、実施例2の方法で分散液を得た。実施例1の方法で皮膜を得て、酸素透過係数(23℃・90%RH)及び水蒸気透過度(40℃・75%RH)を測定した。
表8に示した構成で、水、PVA、BT溶液及びソルビタンモノラウレートを混合し、実施例2の方法で分散液を得た。実施例1の方法で皮膜を得て、酸素透過係数(23℃・90%RH)及び水蒸気透過度(40℃・75%RH)を測定した。
(アスコルビン酸含有錠剤の製造)
酸素及び水蒸気に対するバリア性を評価するために、酸素及び水蒸気に不安定なアスコルビン酸含有錠剤を製造した。
まず、乳糖、結晶セルロース及びヒドロキシプロピルセルロース-SLを攪拌造粒機に投入し、硫酸銅・5水和物を溶解した水で造粒した。得られた造粒物を50℃で終夜乾燥し、コーミルで粉砕し、造粒物Aを得た。その後、造粒物Aとアスコルビン酸を攪拌造粒機に投入し、エタノールで造粒後、50℃で2時間乾燥し、コーミルで粉砕し、造粒物Bを得た。引き続き、造粒物Bと、低置換度ヒドロキシプロピルセルロース、クロスカルメロースナトリウム及びステアリン酸マグネシウムを混合し、ロータリー打錠機(菊水)にて打錠し、アスコルビン酸含有錠剤を得た(直径8mm、12R)。こうして得られたコーティング剤で被覆されていないアスコルビン酸含有錠剤を比較例15とした。
(実施例2の分散液で被覆されたアスコルビン酸含有コーティング錠剤の製造)
比較例15のアスコルビン酸錠剤400gをコーティングパン(Hi-Coater mini;フロイント産業)に仕込み、実施例2で調製した分散液をコーティング剤としてアスコルビン酸含有錠剤に被覆した。コーティング厚みが60μmになるまでコーティング剤を被覆し、アスコルビン酸含有コーティング錠剤を得た。こうして得られた実施例2の分散液で被覆されたアスコルビン酸含有コーティング錠剤を実施例15とした。
(参考例3の分散液で被覆されたアスコルビン酸含有コーティング錠剤の製造)
比較例15のアスコルビン酸含有錠剤400gをコーティングパン(Hi-Coater mini;フロイント産業)に仕込み、参考例3で調製した分散液をコーティング剤として錠剤に被覆した。コーティング厚みが60μmになるまでコーティング剤を被覆した。こうして得られた参考例3の分散液で被覆されたアスコルビン酸含有コーティング錠剤を比較例16とした。
実施例15のアスコルビン酸含有コーティング錠剤の崩壊性を、溶出試験器を用いて評価した。すなわち、アスコルビン酸含有コーティング錠剤1錠を、37℃に加温した水900mLに投入し、皮膜が錠剤表面から剥離し始めるまでに要する時間を測定した。その結果、皮膜が錠剤表面から剥離し始めるまでに要する時間は、約2分であった。この結果、実施例15のアスコルビン酸含有コーティング錠剤は、崩壊性に優れていることが明らかとなり、実施例2の分散液は、徐放性製剤のみならず、速放性製剤への被覆にも適用できることが示唆された。
比較例15のアスコルビン酸含有錠剤並びに実施例15及び比較例16のアスコルビン酸含有コーティング錠剤を、25℃95%RHのデシケータ内で、開放条件下又は気密条件下で4週間保存し、経時的にアスコルビン酸の残存率(薬物残存率)を評価した。開放条件下とは、各錠剤をデシケータ内にそのまま静置することをいい、気密条件下とは、プラスチック製の中蓋と外蓋を有するガラス瓶の中に各錠剤を入れて密封し、密封状態を保持したままでデシケータ内に静置することをいう。
(臭化プロパンテリン含有錠剤の製造)
ガスバリア性を評価するために、無包装状態において極めて不安定であることが知られている臭化プロパンテリン含有錠剤を製造した。臭化プロパンテリン含有錠剤(メサフィリン(登録商標);エーザイ)を吸湿防止のためにドライボクス中で乳鉢を用いて粉砕し、粉砕により得られた錠剤の顆粒をロータリー打錠機(菊水)にて再度打錠し、臭化プロパンテリン含有錠剤を得た(直径8mm、12R)。こうして得られたコーティング剤で被覆されていない臭化プロパンテリン含有錠剤を比較例17とした。
(実施例2の分散液で被覆された臭化プロパンテリン含有コーティング錠剤の製造)
比較例17の臭化プロパンテリン含有錠剤400gをコーティングパン(Hi-Coater mini;フロイント産業)に仕込み、実施例2で調製した分散液をコーティング剤として臭化プロパンテリン含有錠剤に被覆した。コーティング厚みが60μmになるまでコーティング剤で被覆し、臭化プロパンテリン含有コーティング錠剤を得た。こうして得られた臭化プロパンテリン含有コーティング錠剤を実施例16とした。
(市販汎用コーティング処方液で被覆された臭化プロパンテリン含有コーティング錠剤の製造)
蒸留水にヒドロキシプロピルメチルセルロース2910・酸化チタン・マクロゴール400混合物(オパドライOY-7300(登録商標);日本カラコン)を加えて溶解し、市販汎用コーティング処方液を得た。比較例17の臭化プロパンテリン含有錠剤400gをコーティングパン(Hi-Coater mini;フロイント産業)に仕込み、市販汎用コーティング処方液をコーティング剤として錠剤に被覆した。コーティング厚みが60μmになるまでコーティング剤を被覆した。こうして得られた臭化プロパンテリン含有コーティング錠剤を比較例18とした。
(市販防湿処方液で被覆された臭化プロパンテリン含有コーティング錠剤の製造)
蒸留水(875g)にラウリル硫酸ナトリウム(15g)を添加し、完全に溶解するまで攪拌した。次に、アミノアルキルメタクリレートコポリマーE(EudragitEPO(登録商標);デグサ社)(100g)を添加して攪拌し、均一に分散させた段階で、ステアリン酸を(10g)添加し、さらに攪拌することにより市販防湿処方液を得た。比較例17の臭化プロパンテリン含有錠剤400gをコーティングパン(Hi-Coater mini;フロイント産業)に仕込み、市販防湿処方液をコーティング剤として錠剤に被覆した。コーティング厚みが60μmになるまでコーティング剤を被覆した。こうして得られた臭化プロパンテリン含有コーティング錠剤を比較例19とした。
(臭化プロパンテリン糖衣錠剤)
臭化プロパンテリン錠(プロ・バンサイン(登録商標);ファイザー)を臭化プロパンテリン糖衣錠剤として、そのまま比較例20とした。
比較例17の臭化プロパンテリン含有錠剤、実施例16、比較例18及び比較例19の臭化プロパンテリン含有コーティング錠剤、並びに比較例20の臭化プロパンテリン糖衣錠剤の各錠剤をそれぞれ30℃75%RHのデシケータ内で、開放条件下で2箇月間保存し、経時的に臭化プロパンテリンの残存率(薬物残存率)を評価した。ここで、開放条件下とは、ガラス瓶の中に各錠剤を入れ、一切蓋をせずにガラス瓶をデシケータ内にそのまま静置することをいう。
Claims (11)
- 高水素結合性樹脂と、膨潤性粘土と、を含む、固形製剤用のコーティング剤。
- 固形製剤に被覆して乾燥させると、前記膨潤性粘土の積層構造体が面配向し、網目状に分散している皮膜を形成する、請求項1記載のコーティング剤。
- 前記皮膜の縦断面の面積に対する、面配向している前記積層構造体の占める面積の割合が30%以上である、請求項2記載のコーティング剤。
- 前記高水素結合性樹脂と前記膨潤性粘土との質量比は、4:6~6:4である、請求項1~3のいずれか一項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含む、請求項1~3のいずれか一項記載のコーティング剤。
- 前記高水素結合性樹脂と前記膨潤性粘土との質量比は、2:8~5:5である、請求項5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の含有率は、7~35%である、請求項5又は6記載のコーティング剤。
- 前記高水素結合性樹脂は、ポリビニルアルコールである、請求項1~7のいずれか一項記載のコーティング剤。
- 前記膨潤性粘土は、ベントナイトである、請求項1~8のいずれか一項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4~9のいずれか一項記載のコーティング剤。
- 請求項1~10のいずれか一項記載のコーティング剤で被覆された、固形製剤。
Priority Applications (12)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN200980152706.7A CN102256624B (zh) | 2008-12-25 | 2009-12-25 | 固体制剂用的包衣剂以及使用该包衣剂的固体制剂 |
ES09835019.2T ES2664745T3 (es) | 2008-12-25 | 2009-12-25 | Material de revestimiento para una formulación farmacéutica sólida y una formulación farmacéutica solida que utiliza el mismo |
MX2011005687A MX2011005687A (es) | 2008-12-25 | 2009-12-25 | Material de recubrimiento para medicina solida y medicina solida formada con el mismo. |
SI200931824T SI2402035T1 (en) | 2008-12-25 | 2009-12-25 | Coating material for solid pharmaceuticals and solid medicinal products formed with it |
JP2010502107A JP5609639B2 (ja) | 2008-12-25 | 2009-12-25 | 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 |
KR1020117010773A KR101329110B1 (ko) | 2008-12-25 | 2009-12-25 | 고형 제제용 코팅제 및 이것을 사용한 고형 제제 |
BRPI0922670-2A BRPI0922670B1 (pt) | 2008-12-25 | 2009-12-25 | Material de revestimento para uma formulação farmacêutica sólida, e, formulação farmacêutica sólida |
PL09835019T PL2402035T3 (pl) | 2008-12-25 | 2009-12-25 | Materiał powlekający do stałego preparatu farmaceutycznego i stały preparat farmaceutyczny utworzony z jego użyciem |
CA2744008A CA2744008C (en) | 2008-12-25 | 2009-12-25 | Coating material for solid medicine and solid medicine formed with the same |
EP09835019.2A EP2402035B1 (en) | 2008-12-25 | 2009-12-25 | Coating material for solid medicine and solid medicine formed with same |
US13/141,168 US8920818B2 (en) | 2008-12-25 | 2009-12-25 | Coating material for solid medicine and solid medicine formed with same |
US13/796,006 US8900606B2 (en) | 2008-12-25 | 2013-03-12 | Methods of applying coating materials for solid medicines |
Applications Claiming Priority (2)
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JP2008329678 | 2008-12-25 | ||
JP2008-329678 | 2008-12-25 |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
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US13/141,168 A-371-Of-International US8920818B2 (en) | 2008-12-25 | 2009-12-25 | Coating material for solid medicine and solid medicine formed with same |
US13/796,006 Division US8900606B2 (en) | 2008-12-25 | 2013-03-12 | Methods of applying coating materials for solid medicines |
Publications (1)
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WO2010074223A1 true WO2010074223A1 (ja) | 2010-07-01 |
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PCT/JP2009/071573 WO2010074223A1 (ja) | 2008-12-25 | 2009-12-25 | 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 |
Country Status (14)
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US (2) | US8920818B2 (ja) |
EP (1) | EP2402035B1 (ja) |
JP (1) | JP5609639B2 (ja) |
KR (1) | KR101329110B1 (ja) |
CN (1) | CN102256624B (ja) |
BR (1) | BRPI0922670B1 (ja) |
CA (2) | CA2848666C (ja) |
ES (1) | ES2664745T3 (ja) |
HU (1) | HUE038552T2 (ja) |
MX (1) | MX2011005687A (ja) |
PL (1) | PL2402035T3 (ja) |
SI (1) | SI2402035T1 (ja) |
TW (1) | TWI438012B (ja) |
WO (1) | WO2010074223A1 (ja) |
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WO2011065551A1 (ja) * | 2009-11-30 | 2011-06-03 | 東レ株式会社 | 固形製剤用のフィルムコーティング剤及びこれを用いた固形製剤 |
WO2011105539A1 (ja) * | 2010-02-26 | 2011-09-01 | 東レ株式会社 | 被覆固形製剤 |
WO2012029820A1 (ja) | 2010-08-31 | 2012-03-08 | 東レ株式会社 | 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 |
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 |
JP2020002013A (ja) * | 2018-06-25 | 2020-01-09 | 日本酢ビ・ポバール株式会社 | コーティング組成物並びに経口固形剤及びその製造方法 |
JP2020002012A (ja) * | 2018-06-25 | 2020-01-09 | 日本酢ビ・ポバール株式会社 | コーティング組成物並びに経口固形剤及びその製造方法 |
WO2022196818A1 (en) | 2021-03-19 | 2022-09-22 | Ssp Co., Ltd. | Coated solid pharmaceutical preparation |
WO2023224097A1 (ja) * | 2022-05-18 | 2023-11-23 | 東和薬品株式会社 | 膜形成用組成物、膜状組成物及びその利用 |
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JP7414668B2 (ja) * | 2020-08-28 | 2024-01-16 | 信越化学工業株式会社 | ポリビニルアルコール含有造粒物及び固形製剤 |
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Also Published As
Publication number | Publication date |
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US8900606B2 (en) | 2014-12-02 |
US8920818B2 (en) | 2014-12-30 |
PL2402035T3 (pl) | 2018-09-28 |
CA2848666A1 (en) | 2010-07-01 |
EP2402035B1 (en) | 2018-03-21 |
US20110256189A1 (en) | 2011-10-20 |
CA2744008A1 (en) | 2010-07-01 |
CA2848666C (en) | 2016-02-16 |
JP5609639B2 (ja) | 2014-10-22 |
SI2402035T1 (en) | 2018-05-31 |
KR20110066977A (ko) | 2011-06-17 |
JPWO2010074223A1 (ja) | 2012-06-21 |
MX2011005687A (es) | 2011-07-20 |
CA2744008C (en) | 2015-02-10 |
TW201029679A (en) | 2010-08-16 |
US20130189325A1 (en) | 2013-07-25 |
EP2402035A1 (en) | 2012-01-04 |
BRPI0922670A2 (pt) | 2016-01-05 |
EP2402035A4 (en) | 2013-12-11 |
CN102256624A (zh) | 2011-11-23 |
ES2664745T3 (es) | 2018-04-23 |
HUE038552T2 (hu) | 2018-10-29 |
KR101329110B1 (ko) | 2013-11-14 |
CN102256624B (zh) | 2014-12-03 |
BRPI0922670B1 (pt) | 2019-08-06 |
TWI438012B (zh) | 2014-05-21 |
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