WO2017126478A1 - 口腔内保持型崩壊性固形製剤、その製造方法、及び該製造方法に用いる粉体組成物 - Google Patents
口腔内保持型崩壊性固形製剤、その製造方法、及び該製造方法に用いる粉体組成物 Download PDFInfo
- Publication number
- WO2017126478A1 WO2017126478A1 PCT/JP2017/001279 JP2017001279W WO2017126478A1 WO 2017126478 A1 WO2017126478 A1 WO 2017126478A1 JP 2017001279 W JP2017001279 W JP 2017001279W WO 2017126478 A1 WO2017126478 A1 WO 2017126478A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- water
- solid preparation
- soluble polymer
- tablet
- powder composition
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
Definitions
- the present invention relates to an intraoral retention type disintegrating solid preparation which is easily retained in the oral cavity by rapidly becoming a paste in the oral cavity, a method for producing the same, a powder composition used in the production method, and the like About.
- an administration method to absorb an active ingredient (for example, allergy drug) that has been administered by subcutaneous injection until now in the oral mucosa a sublingual liquid preparation, a solid preparation that gradually disintegrates in the oral cavity, and a stomatitis drug
- preparations that start disintegrating in the oral cavity taking appropriate time and oral solid preparations such as lozenges are expected.
- an allergen immunotherapy drug that administers cedar pollen extract under the tongue as a preparation that is a viscous liquid is known. This is because the patient drops himself under the tongue once a day, and then sublingually. It is taken by swallowing after maintaining for about 2 minutes.
- the preparation contains concentrated glycerin, sodium chloride and the like.
- sublingual tablets for desensitization therapy for allergic rhinitis caused by mite antigens
- allergen immunotherapy for example, Asiatica tick sublingual tablets and Mitecure sublingual tablets etc. are known, and these are 10 seconds to several Disintegrates in the oral cavity within minutes.
- sublingual tablets which are drugs that cause angina
- This is disintegrated in about 34 msec after being contained under the tongue, and the effect of nitroglycerin contained as an active ingredient acting directly on the coronary blood vessels to dilate it usually appears in 1 to 2 minutes.
- the preparation contains lactose hydrate, gum arabic, talc, corn starch and the like.
- Patent Document 1 is a patch-like preparation for absorbing the drug into the blood through the oral mucosa. I can do it.
- This preparation is characterized by a layered structure comprising a mucoadhesive layer, a support layer, and two drug layers and an intermediate layer.
- a therapeutic agent for stomatitis and glossitis there is also known a film-like patch that adheres to the oral cavity to protect the affected area from irritation and continuously acts an active ingredient.
- Triethyl acid, hypromellose, ethyl cellulose, castor oil, titanium oxide and the like are included.
- an ointment type as a therapeutic agent for stomatitis and glossitis, and these therapeutic agents for stomatitis and glossitis are held in the oral cavity for 30 to 60 minutes.
- the viscous liquid dripping under the tongue and the type of sublingual tablet are actually difficult to hold under the tongue, and the preparation for intraoral patch such as a film patch Is difficult to apply, and easily peels off depending on the application location (for example, the back of the lower lip).
- the ointment type is applied to the oral cavity by hand, there are problems in terms of hygiene, and it is difficult to apply in public.
- the object of the present invention is to solve such a problem in the prior art, and the present inventors can easily hold in the oral cavity by rapidly disintegrating and forming a paste by saliva in the oral cavity.
- the present invention was completed by solving the above-mentioned problems by providing a solid oral disintegrating solid preparation.
- the present invention provides the following aspects.
- Aspect 5 The solid preparation according to embodiment 4, which contains D-mannitol as a sugar alcohol and crystalline cellulose as a water-insoluble polymer.
- Aspect 6 The solid preparation according to any one of embodiments 1 to 5, further comprising a medicinal component.
- Aspect 7 The solid preparation according to embodiments 1 to 6, which is a tablet having a hardness of 20 N or more.
- Aspect 8 8. The method for producing an intraoral retention type disintegrating solid preparation according to any one of aspects 1 to 7, wherein the powder composition is compression-molded in a dry manner.
- the manufacturing method of aspect 8 including adding and mixing a water-soluble polymer and a medicinal component to the granulated material which consists of components other than water-soluble polymer.
- a powder composition comprising a disintegrating particle composition containing at least one disintegrant and at least one water-soluble polymer for use in the production method according to aspect 8 or 9.
- the oral-holding-type disintegrating solid preparation of the present invention is solid and easy to handle, and can be easily held at any place in the oral cavity when taken. Furthermore, as shown in the examples of the present specification, because of its excellent disintegration property, the solid preparation of the present invention starts to disintegrate within about 40 seconds and rapidly softens by absorbing saliva in the oral cavity. In addition, since it has a good cohesiveness, it is not dispersed and maintains the shape and state of the lump.
- the intraoral retention type disintegrating solid preparation of the present invention does not require a special layer structure or special surface form as in the prior art, and can be easily produced by a simple method. It is.
- the measurement results of the disintegration property of the intraoral retention type disintegrating solid preparations of the present invention are shown.
- the measurement result of the cohesiveness of Example 1 is shown.
- the measurement result of the cohesiveness of Example 2 is shown.
- the measurement result of the cohesiveness of Example 3 is shown.
- the measurement result of the cohesiveness of Example 4 is shown.
- the measurement result of the cohesiveness of Example 5 is shown.
- the measurement result of the cohesiveness of the comparative example 1 is shown.
- the outline of the measurement of disintegration is shown.
- the outline of the measurement of aggregability is shown.
- the present invention contains at least one disintegrant and at least one water-soluble polymer, and the disintegration start time is within 40 seconds, preferably within 35 seconds, more preferably within 30 seconds, and still more preferably.
- the “starting time of disintegration” of the solid preparation is the time required for the swelling to reach the peak value when measured under the conditions described in the present specification (“peak time” described in Table 2). Means. The earlier (shorter) the decay start time, the better (higher) the disintegration. Further, “aggregation” is a characteristic defined based on a value (index) obtained by the measurement method described in the present specification. The larger this value, the higher the cohesion and the more difficult it is to disperse.
- the solid preparation of the present invention starts to disintegrate within about 40 seconds by absorbing saliva in the oral cavity and softens rapidly. Then, it has a feature of becoming a paste, and then maintaining the state and shape of the lump without being dispersed at the place where it is affixed.
- paste-like generally means a fluid semi-solid state.
- any one or more compounds known to those skilled in the art can be used.
- Crospovidone is a common name for a cross-linked polymer of 1-vinyl-2-pyrrolidone
- croscarmellose sodium is a common name for a cross-linked product of sodium carboxymethylcellulose.
- disintegrants for example, carmellose, crospovidone, croscarmellose sodium, low-substituted hydroxypropylcellulose, carboxymethylcellulose calcium and the like are all water-insoluble polymers.
- starch for example, corn starch, potato starch, waxy corn starch, water-insoluble partially pregelatinized starch, and water-insoluble pregelatinized starch are water-insoluble polymers, and as modified starch, for example, sodium starch glycolate and hydroxypropyl starch Modified starch and the like are water-insoluble polymers.
- carmellose and / or crospovidone are preferable.
- water-soluble polymer contained in the composition examples include any one or more compounds known to those skilled in the art, such as sodium carboxymethyl cellulose (also referred to as “carmellose sodium”), sodium alginate, carrageenan, Mention may be made of compounds selected from the group consisting of xanthan gum and gelatin. Natural products or synthetic products may be used.
- a preferred water soluble polymer is carmellose sodium.
- the composition further includes, as an excipient, any sugar alcohol or sugar known to those skilled in the art, and calcium phosphate, hydrous silicon dioxide, anhydrous calcium phosphate, anhydrous calcium hydrogen phosphate, aluminum metasilicate, magnesium silicate, It is preferable to contain light anhydrous silicic acid and inorganic compounds such as magnesium oxide and calcium silicate.
- sugar alcohol or sugar include D-mannitol, mannitol, erythritol, xylitol, trehalose, lactose, maltose, maltitol, glucose, sucrose, fructose, mannose, and sorbitol.
- One kind of sugar or sugar alcohol may be used, but two or more kinds of compounds appropriately selected from these may be used.
- excipient include one or more components selected from the group consisting of D-mannitol, lactose, trehalose, cellulose, xylitol, and calcium phosphate.
- the composition preferably contains a water-insoluble polymer as an excipient for shaping.
- a water-insoluble polymer any substance known to those skilled in the art can be used as long as the moldability of the composition can be effectively improved, and it may be a natural product or a synthetic product.
- water-insoluble polymer examples include, for example, fine fibrous cellulose, crystalline cellulose, powdered cellulose and various cellulose derivatives known to those skilled in the art.
- crystalline cellulose and / or powdered cellulose examples include Avicel (FMC Corporation), Theolas (Asahi Kasei Chemicals Co., Ltd.), Vivapuer (Lettenberg Meyer), etc.
- KC Flock Nippon Paper Chemicals
- ARBOCEL Retttenmeier
- Solka Flock Solka Flock
- the composition contains various optional components known to those skilled in the art, and the effects of the present invention by the above components are included. You may add and mix suitably in the range which does not impair. Examples of such components may include other binders (shaping aids) and functional additives such as fluidizing agents known to those skilled in the art.
- Examples of the fluidizing agent include crystalline cellulose, corn starch, light anhydrous silicic acid, hydrous silicon dioxide, magnesium metasilicate aluminate, magnesium stearate, calcium stearate, stearic acid, magnesium alumina hydroxide, talc and the like.
- the oral-holding disintegrating solid preparation of the present invention includes any form / shape known to those skilled in the art, for example, solid preparations such as tablets, films and sheets. Tablets are particularly preferable.
- the intraoral retention type disintegrating solid preparation of the present invention can appropriately contain any medicinal component (active ingredient) in an appropriate amount.
- the compounding amount of each component in the solid preparation of the present invention can be appropriately determined by those skilled in the art according to the type of each component, the type and use of the preparation, and the like.
- the disintegrant is 1 to 70% by weight and the water-soluble polymer is 0.1 to 30% by weight based on the total weight.
- the amount of the excipient, the water-insoluble polymer, the binder (shaping aid), the functional additive such as a fluidizing agent, and the like can be appropriately determined according to the purpose.
- the oral cavity-holding disintegrating solid preparation of the present invention has excellent disintegration and cohesiveness in the oral cavity, and is a solid preparation that gradually disintegrates in the oral cavity, as well as oral care preparations such as a stomatitis therapeutic agent and the like.
- oral care preparations such as a stomatitis therapeutic agent and the like.
- troche tablets it is used as a pharmaceutical product such as a preparation for oral mucosal absorption.
- it is used as a product for oral care such as various foods including supplementary foods, functional nutritional foods and health foods, and toothpaste.
- the solid preparation of the present invention can further contain optional components.
- a disintegrating particle composition a medicinal component, and arbitrary components
- uses and types of medicinal ingredients contained in the tablet of the present invention include, for example, central nervous system drugs, peripheral nervous system drugs, sensory organ drugs, vaginal cardiovascular drugs, respiratory organ drugs, digestive organ drugs, hormones Drugs, urogenital drugs, other drugs for individual organs, vitamins, nourishing tonics, drugs for blood and body fluids, other metabolic drugs, cell utilization drugs, oncology drugs, radiopharmaceuticals, allergy drugs , Other drugs for tissue cell function, herbal medicine, Kampo medicines, other herbal medicines and medicines based on Kampo medicines, antibiotics, chemotherapeutic agents, biological products, drugs for parasites, drugs for other pathogenic organisms, preparations Medicines, diagnostic drugs, public health drugs, in-vitro diagnostic drugs, and the like.
- various nutritional components such as proteins, carbohydrates, lipids and minerals; various vitamins and their derivatives; health food materials such as various extracts derived from microorganisms, plants or animals; And various items based on Article 10 of the Food Sanitation Law, such as acidulants, sweeteners, excipients, surfactants, lubricants, acidulants, sweeteners, corrigents, fragrances, colorants, and stabilizers ,
- Other optional ingredients that are allowed as food ingredients (food additives) listed in the list of designated additives or existing additives, general food and beverage additives, and the quality and effectiveness of pharmaceuticals, medical devices, etc. It can contain any other ingredients permitted for quasi-drugs listed in the raw material standards for quasi-drugs based on Article 2 of the Act on Ensuring Safety (Former Pharmaceutical Affairs Law). *
- the intraoral retention type disintegrating solid preparation of the present invention can be produced by any method known to those skilled in the art. For example, it can be easily produced by dry-compressing a powder composition containing the above disintegrating particle composition. For example, it can be easily prepared by adding and mixing a water-soluble polymer and a medicinal component to a granulated product composed of components other than the water-soluble polymer.
- the present invention provides a method for producing such an intraoral retention type disintegrating solid preparation, and a disintegration containing at least one disintegrant and at least one water-soluble polymer for use in the production method.
- the present invention also relates to a powder composition containing a conductive particle composition.
- the powder composition can also be produced by any method known to those skilled in the art.
- the granulated product containing a disintegrant, an excipient, a binder and the like can be prepared in advance as a premix type additive composition before mixing with other raw materials.
- Such an additive composition can be produced by mixing various components at once by any method known to those skilled in the art.
- the powder composition can be produced by various granulation process methods by any method known to those skilled in the art. It does not specifically limit as a granulation means, For example, it can also manufacture by a dry granulation method or a wet granulation process method.
- the dry granulation method includes a step of mixing various component powders contained in the powder composition as they are or mixed with an appropriate binder, etc. to form a small mass by high pressure, and appropriately crushing and granulating it.
- Specific examples of the dry granulation method include a crushing granulation method and a roll compression method.
- the wet granulation method is a method of forming a composite by dispersing and drying each component in the presence of water.
- Specific examples of the wet granulation method include spray drying, tumbling granulation, stirring granulation, And spraying methods such as fluidized bed granulation, freeze-drying methods, kneading granulation, and the like, and these can be produced by any method known to those skilled in the art.
- the oral-holding disintegrating solid preparation of the present invention when the oral-holding disintegrating solid preparation of the present invention is a tablet, it has a hardness of 20N or more, preferably 30N or more, more preferably 40N or more.
- the upper limit thereof is not particularly limited as long as the collapse is not significantly delayed, but is, for example, 140N, 130N, or 120N.
- Hardness Hardness (N) was measured using a digital Kiya-type hardness meter (Fujiwara Manufacturing Co., Ltd.). The hardness was measured 6 times, and the average value was taken as the measurement result.
- Disintegration Measured using a dedicated jig Tablet Disintegration Rig (A / TDR) of a texture analyzer (TA.XT plus, manufactured by Stable Microsystems). The outline is shown in FIG. 3.5 mL of water was placed in the A / TDR container, the tablet was attached to the lower end of the probe connected to the load cell with double-sided tape, the probe was lowered, and the point where the tablet contacted the container was set to 0 mm, and measurement was started.
- Cohesiveness Measured using a dedicated Displacement Rig (A / TDR) container of a texture analyzer (TA.XT plus, manufactured by Stable Microsystems) and a resin cylindrical probe with a diameter of 20 mm. The outline is shown in FIG. Water was put into the container of A / TDR, and water was sucked up with a pipette from above the jig with a hole, so that the water at the bottom of the container was supplied only through the hole.
- a / TDR Displacement Rig
- TA.XT plus manufactured by Stable Microsystems
- a resin cylindrical probe having a diameter of 20 mm is inserted from the bottom of the tablet to a height of 10 mm, 7 mm at 2 mm per second, 10 times continuously.
- the stress when compressed was measured.
- a value obtained by dividing the tenth compression stress by the sixth compression stress was used as an index indicating cohesion. Each measurement was performed six times, and the average value was taken as the measurement result.
- Examples 1 to 5 [Production of disintegrating particle composition] 280 g of mannitol (D-mannitol, Merck), 75 g of carmellose (NS-300, Gotoku Pharmaceutical Co., Ltd.), 100 g of crystalline cellulose (Theolas PH-101, Asahi Kasei Chemicals), crospovidone (Polyplastidone INF-10, 40g of ASP Japan Co., Ltd. was put into a fluidized bed granulator (LAB-1, POWREC Co., Ltd.) and 300g of purified water was sprayed at 12g / min to obtain a granulated product.
- the granulated product had the following physical property values. (1) Average particle size: 93 microns, (2) Water content: 2.3% by weight.
- Tablet hardness is 100N using a simple tablet molding machine (HANDTAB-100, Ichihashi Seiki Co., Ltd.) in which a small amount of magnesium stearate (magnesium stearate, Taihei Chemical Industry Co., Ltd.) is applied in advance to the surface of the mortar and upper and lower ridges. Tableting was carried out while adjusting the tableting compression force so as to be before and after, to obtain an intraoral retention type disintegrating solid preparation of the present invention having a diameter of 8.0 mm, a straight tablet and a weight of 250 mg. Their composition and hardness are shown in Table 1. The disintegration measurement results are shown in FIG. 1 and Table 2, and the agglomeration measurement results are shown in FIGS. 2 to 6 and Table 3, respectively.
- [Comparative Example 1] A simple tablet molding machine (HANDTAB-100, Ichibashi) in which a small amount of magnesium stearate (magnesium stearate, Taihei Chemical Industrial Co., Ltd.) was applied as a lubricant to the surfaces of the mortar and upper and lower punches in advance. was used while adjusting the tablet compression force so that the tablet hardness was around 100 N, and a tablet of Comparative Example 1 of the present invention having a diameter of 8.0 mm, a true tablet, and a weight of 250 mg was obtained. .
- Table 1 shows the tablet composition and tablet hardness. The disintegration measurement results are shown in FIG. 1 and Table 2, and the aggregation measurement results are shown in FIG. 7 and Table 3, respectively.
- Tableting was performed while adjusting the tableting compression force so as to be before and after, to obtain a tablet of Comparative Example 2 of the present invention having a diameter of 8.0 mm, a true tablet, and a weight of 250 mg.
- Table 1 shows the tablet composition and tablet hardness.
- the measurement result of disintegration was shown in FIG.
- the cohesiveness could not be measured.
- each tablet obtained in Examples 1 to 5 and Comparative Examples 1 and 2 was taken by three adult men and women. As a result, each tablet obtained in Examples 1 to 5 was softened by saliva in the oral cavity but dispersed. Without maintaining a lump state. On the other hand, the tablet obtained in Comparative Example 1 rapidly disintegrates due to saliva in the oral cavity and does not retain its shape, and the tablet obtained in Comparative Example 2 maintains the hardness of the tablet even when it touches the oral saliva. It was.
- Vitamin C (Vitamin C, Iwaki Pharmaceutical Co., Ltd.) 10 parts by weight was added to and mixed with 90.0 parts by weight of the granulated product obtained in the Example to obtain a mixture.
- Tablet hardness is 100N using a simple tablet molding machine (HANDTAB-100, Ichihashi Seiki Co., Ltd.) in which a small amount of magnesium stearate (magnesium stearate, Taihei Chemical Industry Co., Ltd.) is applied in advance to the surface of the mortar and upper and lower ridges. Tableting was carried out while adjusting the tableting compression force so as to be before and after, to obtain a tablet of Comparative Example 3 of the present invention having a diameter of 8.0 mm, a straight tablet and a weight of 250 mg.
- Comparative Example 4 A solution was prepared by mixing 50 parts by weight of glycerin (glycerin, Nichi-Iko Co., Ltd.), 10 parts by weight of sodium chloride (sodium chloride, Wako Pure Chemical Industries, Ltd.) and 40 parts by weight of purified water. 5 g of vitamin C (vitamin C, Iwaki Pharmaceutical Co., Ltd.) was dissolved in 45 g of a prepared solution to obtain a dropping solution of Comparative Example 4 of the present invention.
- the tablet obtained in Example 5, the tablet obtained in Comparative Example 3, and the dripping liquid (1 mL) obtained in Comparative Example 4 can be taken by each of 6 adult men and women under the tongue and held under the tongue. Time was measured. As a result, it was 61.7 seconds on average in the tablet obtained in Example 5, but 27.3 seconds on average in the tablet obtained in Comparative Example 3, indicating that the sublingual retention time was extended. It was done. In addition, the dripping liquid obtained in Comparative Example 4 spread throughout the mouth at the same time as taking and was difficult to hold under the tongue.
- the present invention includes solid preparations that gradually disintegrate in the oral cavity, oral care preparations such as stomatitis treatment drugs, and pharmaceuticals such as solid preparations for oral mucosal absorption that are used for various uses and purposes such as troche tablets. It greatly contributes to research and development.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Zoology (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
少なくとも1種類の崩壊剤と少なくとも1種類の水溶性高分子を含有し、崩壊の開始時間が40秒以内であり、かつ凝集性を示す指標が0.4以上である、口腔内保持型崩壊性固形製剤。
[態様2]
崩壊剤としてカルメロースを含み、水溶性高分子としてカルメロースナトリウムを含む、態様1記載の固形製剤。
[態様3]
崩壊剤としてカルメロース及びクロスポビドンを含み、水溶性高分子としてカルメロースナトリウムを含む、態様1又は2に記載の固形製剤。
[態様4]
更に、糖アルコール又は糖、及び、水不溶性高分子を含有する、態様1~3のいずれか一項に記載の固形製剤。
[態様5]
糖アルコールとしてD-マンニトール、及び、水不溶性高分子として結晶セルロースを含有する態様4記載の固形製剤。
[態様6]
更に薬効成分を含む、態様1~5のいずれか一項に記載の固形製剤。
[態様7]
20N以上の硬度を有する錠剤である、態様1~6に記載の固形製剤。
[態様8]
粉体組成物を乾式で圧縮成形することを特徴とする、態様1~7に記載の口腔内保持型崩壊性固形製剤の製造方法。
[態様9]
水溶性高分子以外の成分から成る造粒物に水溶性高分子及び薬効成分を添加・混合することを含む、態様8記載の製造方法。
[態様10]
態様8又は9に記載の製造方法に用いるための、少なくとも1種類の崩壊剤と少なくとも1種類の水溶性高分子を含有する崩壊性粒子組成物を含む粉体組成物。
以下の実施例及び比較例で得た造粒物および各錠剤について、組成物の平均粒子径及び水分、並びに、錠剤の硬度、崩壊性、凝集性を以下の条件・方法で測定した。
平均粒子径:粒子組成物5gを、φ75mm自動振とう篩器(Mー3T型、筒井理化学器械株式会社)を用いて測定した。
水分:粒子組成物5gをハロゲン水分測定器(HB43型、メトラートレド株式会社)を用いて測定した。
硬度:デジタル木屋式硬度計(株式会社藤原製作所)を用いて、硬度(N)を測定した。
硬度はそれぞれ6回の測定を行い、それらの平均値を測定結果とした。
崩壊性: テクスチャーアナライザー (TA.XT plus、ステーブルマイクロシステムズ社製)の専用治具Tablet Disintegration Rig (A/TDR)を用いて測定した。その概略を図8に示した。
A/TDRの容器中に3.5mLの水を入れ、ロードセルに連結したプローブ下端に錠剤を両面テープで貼付し、プローブを下降させて錠剤が容器に接した点を0mmとして測定を開始した。測定中は常に40gの荷重がかかるように設定し、プローブ位置の変化を測定した。膨潤(プローブ位置)が最大に達するまでに要した時間を崩壊開始時間とした。それぞれ6回の測定を行い、それらの平均値を測定結果とした。
凝集性: テクスチャーアナライザー (TA.XT plus、ステーブルマイクロシステムズ社製)の専用治具Tablet Disintegration Rig (A/TDR) の容器と直径20mmの樹脂製円柱プローブを用いて測定した。その概略を図9に示した。
A/TDRの容器中に水を入れ、穴の開いた治具の上からピペットで水を吸い上げ、容器底部の水が穴を通ってのみ供給される状態とした。この容器に錠剤をセットして、錠剤全体が吸水した後 (おおよそ20秒から1分後) 、直径20mmの樹脂製円柱プローブを錠剤下端から10mmの高さから毎秒2mmで7mm、10回連続で圧縮した際の応力を測定した。10回目の圧縮時応力を6回目の圧縮時応力で除した値を凝集性を示す指標とした。それぞれ6回の測定を行い、それらの平均値を測定結果とした。
[崩壊性粒子組成物の製造]
マンニトール(D-マンニトール、メルク株式会社)280g、カルメロース(NS-300、五徳薬品株式会社)75g、結晶セルロース(セオラスPH-101、旭化成ケミカルズ株式会社)100g、クロスポビドン(ポリプラスドンINF-10、アイエスピー・ジャパン株式会社)40gを流動層造粒機(LAB-1、株式会社パウレック)に投入し、精製水300gを12g/minにて噴霧することによって、造粒物を得た。尚、造粒物は以下の物性値を有していた。(1)平均粒子径:93ミクロン、(2)水分:2.3重量%。
得られた造粒物98.5 ~ 99.7重量部に、カルメロースナトリウム (CMCダイセル、ダイセルファインケム株式会社) 1.5 ~ 0.3重量部を加え混合し、混合物を得た。また、得られた造粒物88.5重量部に、カルメロースナトリウム (CMCダイセル、ダイセルファインケム株式会社) 1.5重量部、ビタミンC (ビタミンC、岩城製薬株式会社)10重量部を加え混合し、混合物を得た。予め臼および上下杵表面に滑沢剤としてステアリン酸マグネシウム(ステアリン酸マグネシウム、太平化学産業株式会社)を少量塗布した簡易錠剤成形機(HANDTAB-100、市橋精機株式会社)を用いて錠剤硬度が100N前後となるように打錠圧縮力を調整しながら打錠し、直径8.0mm、真平錠、重量250mgの本発明の口腔内保持型崩壊性固形製剤を得た。それらの組成と硬度を表1に示した。また、崩壊性の測定結果を図1および表2に、凝集性の測定結果を図2~6および表3に、それぞれ示した。
実施例で得られた造粒物を、予め臼および上下杵表面に滑沢剤としてステアリン酸マグネシウム(ステアリン酸マグネシウム、太平化学産業株式会社)を少量塗布した簡易錠剤成形機(HANDTAB-100、市橋精機株式会社)を用いて錠剤硬度が100N前後となるように打錠圧縮力を調整しながら打錠し、直径8.0mm、真平錠、重量250mgの本発明の比較例1の錠剤を得た。錠剤組成と錠剤硬度を表1に示した。また、崩壊性の測定結果を図1および表2に、凝集性の測定結果を図7および表3に、それぞれ示した。
乳糖 (FlowLac90、メグレジャパン株式会社) 69.0重量部、コーンスターチ (顆粒コンス、日本コーンスターチ) 29.5重量部、カルメロースナトリウム (CMCダイセル、ダイセルファインケム株式会社) 1.5重量部を混合し、混合物を得た。予め臼および上下杵表面に滑沢剤としてステアリン酸マグネシウム(ステアリン酸マグネシウム、太平化学産業株式会社)を少量塗布した簡易錠剤成形機(HANDTAB-100、市橋精機株式会社)を用いて錠剤硬度が100N前後となるように打錠圧縮力を調整しながら打錠し、直径8.0mm、真平錠、重量250mgの本発明の比較例2の錠剤を得た。錠剤組成と錠剤硬度を表1に示した。また、崩壊性の測定結果を図1に示した。なお、錠剤が崩壊しないため、凝集性は測定できなかった。
実施例で得られた造粒物90.0重量部に、ビタミンC (ビタミンC、岩城製薬株式会社)10重量部を加え混合し、混合物を得た。予め臼および上下杵表面に滑沢剤としてステアリン酸マグネシウム(ステアリン酸マグネシウム、太平化学産業株式会社)を少量塗布した簡易錠剤成形機(HANDTAB-100、市橋精機株式会社)を用いて錠剤硬度が100N前後となるように打錠圧縮力を調整しながら打錠し、直径8.0mm、真平錠、重量250mgの本発明の比較例3の錠剤を得た。
グリセリン (グリセリン、日医工株式会社)50重量部、塩化ナトリウム (塩化ナトリウム、和光純薬株式会社)10重量部、精製水 40重量部を混合した溶液を調製した。5gのビタミンC (ビタミンC、岩城製薬株式会社)を45gの調製溶液に溶解し、本発明の比較例4の滴下用液を得た。
Claims (10)
- 少なくとも1種類の崩壊剤と少なくとも1種類の水溶性高分子を含有し、崩壊の開始時間が40秒以内であり、かつ凝集性を示す指標が0.4以上である、口腔内保持型崩壊性固形製剤。
- 崩壊剤としてカルメロースを含み、水溶性高分子としてカルメロースナトリウムを含む、請求項1記載の固形製剤。
- 崩壊剤としてカルメロース及びクロスポビドンを含み、水溶性高分子としてカルメロースナトリウムを含む、請求項1又は2に記載の固形製剤。
- 更に、糖アルコール又は糖、及び、水不溶性高分子を含有する、請求項1~3のいずれか一項に記載の固形製剤。
- 糖アルコールとしてD-マンニトール、及び、水不溶性高分子として結晶セルロースを含有する請求項4記載の固形製剤。
- 更に薬効成分を含む、請求項1~5のいずれか一項に記載の固形製剤。
- 20N以上の硬度を有する錠剤である、請求項1~6に記載の固形製剤。
- 粉体組成物を乾式で圧縮成形することを特徴とする、請求項1~7に記載の口腔内保持型崩壊性固形製剤の製造方法。
- 水溶性高分子以外の成分から成る造粒物に水溶性高分子及び薬効成分を添加・混合することを含む、請求項8記載の製造方法。
- 請求項8又は9に記載の製造方法に用いるための、少なくとも1種類の崩壊剤と少なくとも1種類の水溶性高分子を含有する崩壊性粒子組成物を含む粉体組成物。
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020187022570A KR20180102114A (ko) | 2016-01-18 | 2017-01-16 | 구강 내 유지형 붕해성 고형 제제, 그 제조방법, 및 상기 제조방법에 이용하는 분체 조성물 |
EP17741356.4A EP3406241A4 (en) | 2016-01-18 | 2017-01-16 | INTRAORAL RESISTANT DISTILLANT SOLUBLE PREPARATION, METHOD FOR THE MANUFACTURE THEREOF, AND POWDER COMPOSITION USED IN THE SAID MANUFACTURING METHOD |
JP2017562810A JP6853191B2 (ja) | 2016-01-18 | 2017-01-16 | 口腔内保持型崩壊性固形製剤、その製造方法、及び該製造方法に用いる粉体組成物 |
US16/067,894 US20200268650A1 (en) | 2016-01-18 | 2017-01-16 | Intraoral retentive disintegrating solid preparation, method for producing same and powder composition used in said production method |
CN201780007145.6A CN108463216B (zh) | 2016-01-18 | 2017-01-16 | 口腔内保持型崩解性固体制剂、其制造方法和用于该制造方法的粉体组合物 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2016007031 | 2016-01-18 | ||
JP2016-007031 | 2016-03-30 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2017126478A1 true WO2017126478A1 (ja) | 2017-07-27 |
Family
ID=59361607
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2017/001279 WO2017126478A1 (ja) | 2016-01-18 | 2017-01-16 | 口腔内保持型崩壊性固形製剤、その製造方法、及び該製造方法に用いる粉体組成物 |
Country Status (7)
Country | Link |
---|---|
US (1) | US20200268650A1 (ja) |
EP (1) | EP3406241A4 (ja) |
JP (1) | JP6853191B2 (ja) |
KR (1) | KR20180102114A (ja) |
CN (1) | CN108463216B (ja) |
TW (1) | TWI703989B (ja) |
WO (1) | WO2017126478A1 (ja) |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002179558A (ja) * | 2000-10-06 | 2002-06-26 | Takeda Chem Ind Ltd | 固形製剤 |
JP2010516684A (ja) * | 2007-01-22 | 2010-05-20 | ターガセプト・インコーポレイテッド | メタニコチンアナログの鼻腔内、バッカル、または舌下投与 |
JP2010138124A (ja) | 2008-12-12 | 2010-06-24 | Kyukyu Yakuhin Kogyo Kk | 口腔内粘膜貼付製剤 |
JP2011210817A (ja) | 2010-03-29 | 2011-10-20 | Canon Inc | 薄膜トランジスタの製造方法 |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7510728B2 (en) * | 2000-10-06 | 2009-03-31 | Takeda Pharmaceutical Company Limited | Solid preparations |
CN101636147A (zh) * | 2007-01-22 | 2010-01-27 | 塔加西普特公司 | 位变异构烟碱类似物的鼻内、经颊和舌下给药 |
JP5537927B2 (ja) * | 2007-03-13 | 2014-07-02 | 大日本住友製薬株式会社 | 口腔内崩壊錠 |
AU2009258560B2 (en) * | 2008-06-13 | 2014-07-10 | Sumitomo Pharma Co., Ltd. | Tablet quickly disintegrating in the oral cavity and method for producing the same |
JP2010241760A (ja) * | 2009-04-09 | 2010-10-28 | Takada Seiyaku Kk | 不快な味の軽減された口腔内速崩壊錠及びその製造方法 |
US9446055B2 (en) * | 2009-08-11 | 2016-09-20 | Fuji Chemical Industry Co., Ltd. | Disintegrating particle composition and orally rapidly disintegrating tablet |
JP2011111418A (ja) * | 2009-11-27 | 2011-06-09 | Toyo Capsule Kk | 口腔内局所投与に適したウイルス感染予防製剤 |
JP2011201817A (ja) | 2010-03-26 | 2011-10-13 | Nrl Pharma Inc | 口腔貼付用錠剤 |
JP5775223B2 (ja) * | 2012-09-05 | 2015-09-09 | テイカ製薬株式会社 | 口腔内速崩壊性錠剤用造粒物 |
US10292934B2 (en) * | 2012-09-20 | 2019-05-21 | Daicel Corporation | Disintegrating particle composition containing acid-type carboxymethylcellulose and crystalline cellulose, and orally disintegrating tablet containing said composition |
JP2015098470A (ja) * | 2013-10-17 | 2015-05-28 | 塩野義製薬株式会社 | ロキソプロフェン又はその塩を含有する錠剤 |
-
2017
- 2017-01-16 EP EP17741356.4A patent/EP3406241A4/en active Pending
- 2017-01-16 CN CN201780007145.6A patent/CN108463216B/zh active Active
- 2017-01-16 KR KR1020187022570A patent/KR20180102114A/ko not_active Application Discontinuation
- 2017-01-16 WO PCT/JP2017/001279 patent/WO2017126478A1/ja active Application Filing
- 2017-01-16 JP JP2017562810A patent/JP6853191B2/ja active Active
- 2017-01-16 TW TW106101374A patent/TWI703989B/zh active
- 2017-01-16 US US16/067,894 patent/US20200268650A1/en not_active Abandoned
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002179558A (ja) * | 2000-10-06 | 2002-06-26 | Takeda Chem Ind Ltd | 固形製剤 |
JP2010516684A (ja) * | 2007-01-22 | 2010-05-20 | ターガセプト・インコーポレイテッド | メタニコチンアナログの鼻腔内、バッカル、または舌下投与 |
JP2010138124A (ja) | 2008-12-12 | 2010-06-24 | Kyukyu Yakuhin Kogyo Kk | 口腔内粘膜貼付製剤 |
JP2011210817A (ja) | 2010-03-29 | 2011-10-20 | Canon Inc | 薄膜トランジスタの製造方法 |
Non-Patent Citations (3)
Title |
---|
ANONYMOUS: "Huoipan Tablets 1OOmg package insert (translated)", FOIPAN-JO 100MG TENPU BUNSHO, 2011, JP, pages 1 - 3, XP009513561 * |
NORIYUKI SUDA ET AL.: "Development and Evaluation of Rapidly Disintegrating Tablets Containing Camostat Mesilate for the Prevention of Occurrence of Stomatitis during Cancer Chemotherapy", JPN. J. PHARM. HEALTH CARE SCI., vol. 29, no. 6, 2003, pages 705 - 710, XP055531075 * |
See also references of EP3406241A4 |
Also Published As
Publication number | Publication date |
---|---|
CN108463216A (zh) | 2018-08-28 |
TWI703989B (zh) | 2020-09-11 |
CN108463216B (zh) | 2021-12-31 |
US20200268650A1 (en) | 2020-08-27 |
JPWO2017126478A1 (ja) | 2018-11-08 |
KR20180102114A (ko) | 2018-09-14 |
EP3406241A1 (en) | 2018-11-28 |
JP6853191B2 (ja) | 2021-03-31 |
EP3406241A4 (en) | 2019-06-26 |
TW201729798A (zh) | 2017-09-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
TW586941B (en) | Quickly disintegratable pharmaceutical composition | |
JP2020125358A (ja) | 口腔内崩壊錠 | |
TWI695722B (zh) | 固態製劑之外層用組成物及含有該外層用組成物之易服用性固態製劑 | |
TWI733650B (zh) | 含微小纖維狀之纖維素之崩解性粒子組成物 | |
TWI705832B (zh) | 易服用性固態製劑用粒子組成物及含有該粒子組成物之易服用性固態製劑 | |
KR102377914B1 (ko) | 분쇄 유당 또는 조립 유당을 포함하는 붕해성 입자 조성물 | |
JP2019131597A (ja) | 超速崩壊錠剤及びその製造方法 | |
TWI673069B (zh) | 超高速崩解錠劑及其製造方法 | |
TWI762450B (zh) | 超高速崩解錠劑及其製造方法 | |
JP2002308760A (ja) | 圧縮成型用組成物及びその利用 | |
WO2017126478A1 (ja) | 口腔内保持型崩壊性固形製剤、その製造方法、及び該製造方法に用いる粉体組成物 | |
WO2016098459A1 (ja) | 遅延崩壊性粒子組成物 | |
JP6615595B2 (ja) | 口腔内崩壊性シート状製剤 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 17741356 Country of ref document: EP Kind code of ref document: A1 |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2017562810 Country of ref document: JP |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
ENP | Entry into the national phase |
Ref document number: 20187022570 Country of ref document: KR Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1020187022570 Country of ref document: KR |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2017741356 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref document number: 2017741356 Country of ref document: EP Effective date: 20180820 |