JP2017114791A - Methods of producing tablets, methods of producing granules for tablet raw materials, and granules for tablet raw materials - Google Patents
Methods of producing tablets, methods of producing granules for tablet raw materials, and granules for tablet raw materials Download PDFInfo
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- JP2017114791A JP2017114791A JP2015249993A JP2015249993A JP2017114791A JP 2017114791 A JP2017114791 A JP 2017114791A JP 2015249993 A JP2015249993 A JP 2015249993A JP 2015249993 A JP2015249993 A JP 2015249993A JP 2017114791 A JP2017114791 A JP 2017114791A
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- tablet
- granules
- gas
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- liquid
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- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Landscapes
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- General Preparation And Processing Of Foods (AREA)
- Jellies, Jams, And Syrups (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
本発明は、賦形剤、結合剤、及び崩壊剤の少なくともいずれかと、崩壊性に劣る原料とを含む錠剤の製造方法、並びに前記錠剤の製造方法に好適な賦形剤、結合剤、及び崩壊剤の少なくともいずれかの顆粒の製造方法、及び錠剤原料用の賦形剤、結合剤、及び崩壊剤の少なくともいずれかの顆粒に関する。 The present invention relates to a method for producing a tablet comprising at least one of an excipient, a binder, and a disintegrant and a raw material that is inferior in disintegration, and an excipient, a binder, and a disintegration suitable for the tablet production method. The present invention relates to a method for producing granules of at least one of the agents, and granules of at least one of excipients, binders, and disintegrants for tablet raw materials.
サプリメントなどに使用する原料の中には、例えば、植物抽出エキス、動物又は魚介類からの抽出エキスなどのような、崩壊時間が長くなる傾向を有するような原料(以下、「崩壊性に劣る原料」と称することがある)が存在する。 Among the raw materials used for supplements and the like, for example, raw materials that tend to have a long decay time, such as plant extracts, extracts from animals or seafood (hereinafter referred to as “raw materials with poor disintegration”) May be referred to as “)”.
崩壊性に劣る原料を含む錠剤では、その崩壊性を改善するために、崩壊剤を多量に配合する必要がある。しかしながら、崩壊剤の配合量が多くなり過ぎると、錠剤硬度が低下し、製品品質に影響を及ぼしてしまうという問題がある。
また、結晶セルロース、デキストリン、糖アルコールなどを多量に配合することで錠剤の崩壊性を担保している場合もある。
しかしながら、これらの対応では、賦形剤、結合剤、及び崩壊剤の少なくともいずれかを多く配合する必要があるため、その結果、錠剤の1日目安粒数が多くなってしまったり、1粒当たりの重量が大きくなり、飲み込みにくくなってしまったりするという問題がある。
In the case of a tablet containing a raw material that is inferior in disintegrability, a large amount of disintegrant needs to be blended in order to improve the disintegration property. However, when the blending amount of the disintegrant is too large, there is a problem that the tablet hardness is lowered and the product quality is affected.
In some cases, disintegration of the tablet is ensured by blending a large amount of crystalline cellulose, dextrin, sugar alcohol, and the like.
However, in these measures, it is necessary to add a large amount of at least one of an excipient, a binder, and a disintegrant, and as a result, the number of tablets per day is increased, or per tablet There is a problem that the weight of the bottle becomes large and it becomes difficult to swallow.
したがって、崩壊性に劣る原料を含む場合であっても、十分な錠剤硬度を得ることができ、かつ崩壊性に優れた錠剤を簡易に効率良く製造することができる錠剤の製造方法、並びに前記錠剤の製造に好適に用いることができる錠剤原料用顆粒及びその製造方法の速やかな提供が強く求められているのが現状である。 Therefore, even when a raw material that is inferior in disintegration is contained, a method for producing a tablet that can obtain sufficient tablet hardness and can easily and efficiently produce a tablet that is excellent in disintegration, and the tablet At present, there is a strong demand for prompt provision of granules for tablet raw materials that can be suitably used in the production of the above and a method for producing the same.
なお、粉末クリームの製造法として、噴霧乾燥法の1つであるガスインジェクション法を用いる技術が提案されている(例えば、特許文献1参照)。しかしながら、前記提案では、賦形剤、結合剤、及び崩壊剤の少なくともいずれかと、崩壊性に劣る原料とを含む錠剤の製造において、スプレードライガスインジェクション法を用いることについては、何ら記載されていない。 In addition, as a method for producing a powder cream, a technique using a gas injection method which is one of spray drying methods has been proposed (for example, see Patent Document 1). However, the proposal does not describe any use of the spray dry gas injection method in the manufacture of a tablet containing at least one of an excipient, a binder, and a disintegrant and a raw material that is inferior in disintegration. .
本発明は、従来における前記諸問題を解決し、以下の目的を達成することを課題とする。即ち、本発明は、崩壊性に劣る原料を含む場合であっても、十分な錠剤硬度を得ることができ、かつ崩壊性に優れた錠剤を簡易に効率良く製造することができる錠剤の製造方法、並びに前記錠剤の製造に好適に用いることができる錠剤原料用顆粒及びその製造方法を提供することを目的とする。 An object of the present invention is to solve the above-described problems and achieve the following objects. That is, the present invention provides a tablet production method capable of obtaining a tablet having sufficient tablet hardness and capable of easily and efficiently producing a tablet excellent in disintegration even when a raw material having poor disintegration is included. It is another object of the present invention to provide granules for tablet raw materials that can be suitably used for the production of tablets and a method for producing the same.
前記課題を解決するための手段としては、以下の通りである。即ち、
<1> 賦形剤、結合剤、及び崩壊剤の少なくともいずれかを含む液体にガスを注入し、ガス含有液体を調製する工程と、
前記ガス含有液体を噴霧乾燥し、顆粒を調製する工程と、
前記顆粒と、崩壊性に劣る原料とを含む混合物を打錠し、錠剤を調製する工程とを含むことを特徴とする錠剤の製造方法である。
<2> (A)ガスの注入量(mL/分)と、(B)賦形剤、結合剤、及び崩壊剤の少なくともいずれかを含む液体の送液量(mL/分)との比((A)/(B))が、0.5〜60である前記<1>に記載の錠剤の製造方法である。
<3> ガスが、窒素ガスである前記<1>から<2>のいずれかに記載の錠剤の製造方法である。
<4> 錠剤原料用の賦形剤、結合剤、及び崩壊剤の少なくともいずれかの顆粒の製造方法であって、
賦形剤、結合剤、及び崩壊剤の少なくともいずれかを含む液体にガスを注入し、ガス含有液体を調製する工程と、
前記ガス含有液体を噴霧乾燥し、顆粒を調製する工程とを含むことを特徴とする錠剤原料用顆粒の製造方法である。
<5> (A)ガスの注入量(mL/分)と、(B)賦形剤、結合剤、及び崩壊剤の少なくともいずれかを含む液体の送液量(mL/分)との比((A)/(B))が、0.5〜60である前記<4>に記載の錠剤原料用顆粒の製造方法である。
<6> ガスが、窒素ガスである前記<4>から<5>のいずれかに記載の錠剤原料用顆粒の製造方法である。
<7> 錠剤原料用の賦形剤、結合剤、及び崩壊剤の少なくともいずれかの顆粒であって、
前記顆粒のかさ密度が、顆粒とする前の原料のかさ密度の40%〜90%であり、
前記顆粒のメディアン径が、140μm〜240μmであることを特徴とする錠剤原料用顆粒である。
Means for solving the problems are as follows. That is,
<1> Injecting a gas into a liquid containing at least one of an excipient, a binder, and a disintegrant to prepare a gas-containing liquid;
Spray-drying the gas-containing liquid to prepare granules;
A tablet manufacturing method comprising tableting a mixture containing the granule and a raw material inferior in disintegrability to prepare a tablet.
<2> Ratio of (A) gas injection amount (mL / min) and (B) liquid feed amount (mL / min) containing at least one of excipient, binder and disintegrant ( (A) / (B)) is the manufacturing method of the tablet as described in said <1> which is 0.5-60.
<3> The method for producing a tablet according to any one of <1> to <2>, wherein the gas is nitrogen gas.
<4> A method for producing granules of at least one of excipients, binders, and disintegrants for tablet raw materials,
Injecting a gas into a liquid containing at least one of an excipient, a binder, and a disintegrant to prepare a gas-containing liquid;
And a step of spray-drying the gas-containing liquid to prepare granules.
<5> Ratio of (A) gas injection amount (mL / min) to (B) liquid feed amount (mL / min) containing at least one of excipient, binder and disintegrant ( (A) / (B)) is a manufacturing method of the granule for tablet raw materials as described in said <4> which is 0.5-60.
<6> The method for producing a granule for tablet raw material according to any one of <4> to <5>, wherein the gas is nitrogen gas.
<7> Granules of at least one of excipients, binders, and disintegrants for tablet raw materials,
The bulk density of the granules is 40% to 90% of the bulk density of the raw material before the granules,
The granule for tablet raw material, wherein the granule has a median diameter of 140 μm to 240 μm.
本発明によれば、従来における前記諸問題を解決し、前記目的を達成することができ、崩壊性に劣る原料を含む場合であっても、十分な錠剤硬度を得ることができ、かつ崩壊性に優れた錠剤を簡易に効率良く製造することができる錠剤の製造方法、並びに前記錠剤の製造に好適に用いることができる錠剤原料用顆粒及びその製造方法を提供することができる。 According to the present invention, the conventional problems can be solved, the object can be achieved, and sufficient tablet hardness can be obtained even when the raw material is inferior in disintegration, and disintegration is achieved. It is possible to provide a tablet production method capable of easily and efficiently producing excellent tablets, a tablet raw material granule that can be suitably used for the production of the tablet, and a production method thereof.
(錠剤の製造方法)
本発明の錠剤の製造方法は、ガス含有液体調製工程と、顆粒調製工程と、錠剤調製工程とを少なくとも含み、必要に応じて更にその他の工程を含む。
(Tablet production method)
The tablet production method of the present invention includes at least a gas-containing liquid preparation step, a granule preparation step, and a tablet preparation step, and further includes other steps as necessary.
<ガス含有液体調製工程>
前記ガス含有液体調製工程は、賦形剤、結合剤、及び崩壊剤の少なくともいずれかを含む液体にガスを注入し、ガス含有液体を調製する工程である。
<Gas-containing liquid preparation process>
The gas-containing liquid preparation step is a step of preparing a gas-containing liquid by injecting a gas into a liquid containing at least one of an excipient, a binder, and a disintegrant.
−賦形剤、結合剤、及び崩壊剤の少なくともいずれかを含む液体−
前記液体は、賦形剤、結合剤、及び崩壊剤の少なくともいずれかを含み、必要に応じて更にその他の成分を含む。
前記液体は、賦形剤、結合剤、及び崩壊剤のうち、賦形剤のみを含む態様であってもよいし、結合剤のみを含む態様であってもよいし、崩壊剤のみを含む態様であってもよいし、これらの2種以上を含む態様であってもよい。
-Liquid containing at least one of excipients, binders, and disintegrants-
The liquid contains at least one of an excipient, a binder, and a disintegrant, and further contains other components as necessary.
The liquid may be in an embodiment containing only the excipient among the excipient, binder and disintegrant, in an embodiment containing only the binder, or in an embodiment containing only the disintegrant. It may be a mode including two or more of these.
−−賦形剤−−
前記賦形剤としては、特に制限はなく、目的に応じて適宜選択することができ、例えば、コーンスターチなどの澱粉類、澱粉分解物、結晶セルロース、糖アルコール、乳糖、ビール酵母などが挙げられる。これらは、1種単独で使用してもよいし、2種以上を併用してもよい。
前記賦形剤は、市販品を使用することができる。
--Excipient--
There is no restriction | limiting in particular as said excipient | filler, According to the objective, it can select suitably, For example, starches, such as corn starch, starch degradation product, crystalline cellulose, sugar alcohol, lactose, brewer's yeast etc. are mentioned. These may be used individually by 1 type and may use 2 or more types together.
A commercially available product can be used as the excipient.
−−結合剤−−
前記結合剤としては、特に制限はなく、目的に応じて適宜選択することができ、例えば、グアーガム;結晶セルロース;結晶セルロース・軽質無水ケイ酸(結晶セルロースに軽質無水ケイ酸を付着させたもの);ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース等のセルロース誘導体;キシリトール、ソルビトール、マンニトール、マルチトール等の糖アルコール;還元麦芽糖水あめ;還元パラチノースなどが挙げられる。これらは、1種単独で使用してもよいし、2種以上を併用してもよい。
前記結合剤は、市販品を使用することができる。
--Binder--
There is no restriction | limiting in particular as said binder, According to the objective, it can select suitably, For example, guar gum; crystalline cellulose; crystalline cellulose and light anhydrous silicic acid (what attached light anhydrous silicic acid to crystalline cellulose) Cellulose derivatives such as hydroxypropylcellulose and hydroxypropylmethylcellulose; sugar alcohols such as xylitol, sorbitol, mannitol and maltitol; reduced maltose starch syrup; reduced palatinose and the like. These may be used individually by 1 type and may use 2 or more types together.
A commercial item can be used for the binder.
−−崩壊剤−−
前記崩壊剤としては、特に制限はなく、目的に応じて適宜選択することができ、例えば、部分α化澱粉、寒天、低置換度ヒドロキシプロピルセルロース、カルメロース、カルボキシメチルスターチナトリウム、クロスポビドン、クロスカルメロースナトリウムなどが挙げられる。これらは、1種単独で使用してもよいし、2種以上を併用してもよい。
前記崩壊剤は、市販品を使用することができる。
-Disintegrant-
The disintegrant is not particularly limited and may be appropriately selected depending on the intended purpose. For example, partially pregelatinized starch, agar, low-substituted hydroxypropylcellulose, carmellose, sodium carboxymethyl starch, crospovidone, croscarmone Examples include sodium loin. These may be used individually by 1 type and may use 2 or more types together.
A commercially available product can be used as the disintegrant.
前記賦形剤、結合剤、及び崩壊剤の少なくともいずれかの前記液体における含有量としては、特に制限はなく、目的に応じて適宜選択することができるが、5質量%〜60質量%が好ましく、10質量%〜50質量%がより好ましく、20質量%〜40質量%が特に好ましい。前記含有量が5質量%未満であると、必要量の乾燥原料を得るために時間を要することがあり、60質量%を超えると、十分に溶解されない状態の原料が残り、目的の乾燥原料とならないことがあったり、液体の粘度が高くなり、後の噴霧乾燥処理に支障をきたすことがある。一方、前記含有量が前記好ましい範囲内であると、適量の空隙を保持した顆粒を得ることが出来、且つ流動性の良い原料を効率良く得ることが出来る点で、有利である。
前記賦形剤、結合剤、及び崩壊剤を2種以上用いる場合の各成分の比率としては、特に制限はなく、目的に応じて適宜選択することができる。
There is no restriction | limiting in particular as content in the said liquid of at least any one of the said excipient | filler, binder, and a disintegrating agent, Although it can select suitably according to the objective, 5 mass%-60 mass% are preferable. 10 mass%-50 mass% are more preferable, and 20 mass%-40 mass% are especially preferable. When the content is less than 5% by mass, it may take time to obtain a necessary amount of dry raw material. When the content exceeds 60% by mass, a raw material that is not sufficiently dissolved remains, and the desired dry raw material In some cases, the viscosity of the liquid may increase, and the subsequent spray drying process may be hindered. On the other hand, when the content is within the preferable range, it is advantageous in that a granule retaining an appropriate amount of voids can be obtained and a raw material having good fluidity can be obtained efficiently.
The ratio of each component when two or more of the excipient, binder, and disintegrant are used is not particularly limited and can be appropriately selected according to the purpose.
−−その他の成分−−
前記液体におけるその他の成分としては、本発明の効果を損なわない限り、特に制限はなく、目的に応じて適宜選択することができ、例えば、ヒドロキシセルロース、ヒドロキシメチルセルロース、ヒドロキシプロピルメチルセルロース等のセルロース誘導体、ジェランガム、プルラン等の増粘多糖類、デキストリン等の澱粉分解物などが挙げられる。
前記その他の成分は、市販品を使用することができる。
前記その他の前記液体における含有量としては、特に制限はなく、目的に応じて適宜選択することができる。
-Other ingredients-
The other components in the liquid are not particularly limited as long as the effects of the present invention are not impaired, and can be appropriately selected according to the purpose. Examples thereof include cellulose derivatives such as hydroxycellulose, hydroxymethylcellulose, hydroxypropylmethylcellulose, Examples include thickening polysaccharides such as gellan gum and pullulan, and starch degradation products such as dextrin.
Commercially available products can be used as the other components.
There is no restriction | limiting in particular as content in the said other said liquid, According to the objective, it can select suitably.
−−溶媒−−
前記液体の溶媒としては、特に制限はなく、目的に応じて適宜選択することができ、例えば、水、水にエタノールを溶解した溶媒などが挙げられる。
前記溶媒の温度としては、特に制限はなく、目的に応じて適宜選択することができる。
--Solvent--
There is no restriction | limiting in particular as said liquid solvent, According to the objective, it can select suitably, For example, the solvent etc. which melt | dissolved ethanol in water are mentioned.
There is no restriction | limiting in particular as temperature of the said solvent, According to the objective, it can select suitably.
−ガス−
前記ガスの種類としては、特に制限はなく、目的に応じて適宜選択することができ、例えば、窒素ガス、炭酸ガス、亜酸化窒素ガス、空気などが挙げられる。これらは、1種単独で使用してもよいし、2種以上を併用してもよい。
前記ガスの中でも、窒素ガスが、製品品質保証の点で、好ましい。
-Gas-
There is no restriction | limiting in particular as a kind of said gas, According to the objective, it can select suitably, For example, nitrogen gas, a carbon dioxide gas, nitrous oxide gas, air etc. are mentioned. These may be used individually by 1 type and may use 2 or more types together.
Among the gases, nitrogen gas is preferable in terms of product quality assurance.
−−注入−−
前記ガスの注入量としては、特に制限はなく、前記賦形剤、結合剤、及び崩壊剤の少なくともいずれかを含む液体の送液量に応じて適宜選択することができる。
--Injection--
There is no restriction | limiting in particular as injection amount of the said gas, According to the liquid feeding amount of the liquid containing at least any one of the said excipient | filler, binder, and a disintegrating agent, it can select suitably.
前記ガスの注入方法としては、特に制限はなく、公知の手段を目的に応じて適宜選択することができ、例えば、一般的な噴霧乾燥装置にガス注入装置を組み合わせて使用する方法などが挙げられる。
前記噴霧乾燥装置としては、例えば、Micra Spray(Anhydro社製)、MOBILE MINOR Spray Dryer(GEA社製)などが挙げられる。
前記ガス注入装置としては、例えば、ADS(Anhydro社製)などが挙げられる。
The gas injection method is not particularly limited and may be appropriately selected from known means according to the purpose. Examples thereof include a method of using a gas injection device in combination with a general spray drying device. .
Examples of the spray drying device include Micra Spray (manufactured by Anhydro), MOBILE MINOR Spray Dryer (manufactured by GEA), and the like.
Examples of the gas injection device include ADS (manufactured by Anhydro).
前記ガスを注入する際の前記賦形剤、結合剤、及び崩壊剤の少なくともいずれかを含む液体の送液量としては、特に制限はなく、目的に応じて適宜選択することができる。 There is no restriction | limiting in particular as a liquid feeding amount of the liquid containing at least any one of the said excipient | filler at the time of inject | pouring the said gas, binder, and a disintegrating agent, According to the objective, it can select suitably.
前記ガスの注入量(mL/分)(A)と、前記賦形剤、結合剤、及び崩壊剤の少なくともいずれかを含む液体の送液量(mL/分)(B)との比((A)/(B))としては、特に制限はなく、目的に応じて適宜選択することができるが、0.5〜60が好ましく、9〜50がより好ましく、15〜45が特に好ましい。前記比((A)/(B))が0.5未満であると、乾燥原料中に十分な空隙が保持できないことがあり、60を超えると、空隙の大きさが大きくなり、十分な空隙を保持した顆粒とはならず、また流動性も低下する原料となることがある。 The ratio of the gas injection amount (mL / min) (A) to the liquid feed rate (mL / min) (B) of the liquid containing at least one of the excipient, binder and disintegrant (( There is no restriction | limiting in particular as A) / (B)), Although it can select suitably according to the objective, 0.5-60 are preferable, 9-50 are more preferable, and 15-45 are especially preferable. When the ratio ((A) / (B)) is less than 0.5, sufficient voids may not be retained in the dry raw material. When the ratio exceeds 60, the size of the voids increases and sufficient voids are obtained. It may not be a granule that retains the viscosity, and may become a raw material with reduced fluidity.
<顆粒調製工程>
前記顆粒調製工程は、前記ガス含有液体を噴霧乾燥し、顆粒を調製する工程である。前記調製された顆粒は、多孔質な顆粒である。
<Granule preparation process>
The granule preparation step is a step of preparing granules by spray drying the gas-containing liquid. The prepared granule is a porous granule.
−−噴霧乾燥−−
前記噴霧乾燥の方法としては、特に制限はなく、公知の噴霧乾燥装置を目的に応じて適宜選択することができる。
前記噴霧乾燥装置の具体例としては、上記した噴霧乾燥装置と同様のものが挙げられる。
--- Spray drying-
There is no restriction | limiting in particular as said spray-drying method, A well-known spray-drying apparatus can be suitably selected according to the objective.
Specific examples of the spray drying device include the same spray drying devices as those described above.
前記噴霧乾燥の条件としては、特に制限はなく、目的に応じて適宜選択することができる。 The spray drying conditions are not particularly limited and can be appropriately selected depending on the purpose.
<錠剤調製工程>
前記錠剤調製工程は、前記顆粒と、崩壊性に劣る原料とを含む混合物(以下、「打錠末」と称することがある)を打錠し、錠剤を調製する工程である。
<Tablet preparation process>
The tablet preparation step is a step of preparing a tablet by tableting a mixture (hereinafter sometimes referred to as “tablet powder”) containing the granule and a raw material inferior in disintegrability.
−混合物−
前記混合物は、前記顆粒と、崩壊性に劣る原料とを少なくとも含み、必要に応じて更にその他の成分を含む。
-Mixture-
The mixture includes at least the granule and a raw material that is inferior in disintegration, and further includes other components as necessary.
−−顆粒−−
前記顆粒は、前記賦形剤、結合剤、及び崩壊剤のうち、賦形剤のみを含む態様であってもよいし、結合剤のみを含む態様であってもよいし、崩壊剤のみを含む態様であってもよいし、これらの2種以上を含む態様であってもよい。前記賦形剤、結合剤、及び崩壊剤を2種以上用いる場合の各成分の比率としては、特に制限はなく、目的に応じて適宜選択することができる。
前記顆粒の前記混合物における含有量としては、特に制限はなく、目的に応じて適宜選択することができるが、5質量%〜90質量%が好ましく、10質量%〜80質量%がより好ましく、15質量%〜70質量%が特に好ましい。前記含有量が、5質量%未満であると、錠剤硬度及び崩壊時間への寄与度が少なく、目的の効果を示さないことがあり、90質量%を超えると、配合成分含量が少なくなり、錠剤重量が増えて飲み込みにくい錠剤になることがある。一方、前記含有量が前記好ましい範囲内であると、より適度な錠剤硬度と、より早い崩壊時間とを併せ持つ錠剤を得ることが出来る点で、有利である。
--- Granules-
The granule may be an embodiment containing only the excipient among the excipient, binder, and disintegrant, may be an embodiment containing only the binder, or contains only the disintegrant. An aspect may be sufficient and the aspect containing these 2 or more types may be sufficient. The ratio of each component when two or more of the excipient, binder, and disintegrant are used is not particularly limited and can be appropriately selected according to the purpose.
There is no restriction | limiting in particular as content in the said mixture of the said granule, Although it can select suitably according to the objective, 5 mass%-90 mass% are preferable, 10 mass%-80 mass% are more preferable, 15 A mass% to 70 mass% is particularly preferred. When the content is less than 5% by mass, the contribution to the tablet hardness and disintegration time is small and the intended effect may not be exhibited. When the content exceeds 90% by mass, the content of the blended components decreases, and the tablet It may become a tablet that increases in weight and is difficult to swallow. On the other hand, when the content is within the preferable range, it is advantageous in that a tablet having a more appropriate tablet hardness and a faster disintegration time can be obtained.
−−崩壊性に劣る原料−−
前記崩壊性に劣る原料としては、特に制限はなく、目的に応じて適宜選択することができ、植物抽出エキス、動物又は魚介類からの抽出エキス、水に溶けにくい原料、グルコサミンなどが挙げられる。これらは、1種単独で使用してもよいし、2種以上を併用してもよい。
前記植物抽出エキスの具体例としては、マカ抽出物、秋ウコン抽出物、春ウコン抽出物、グアーガムなどが挙げられる。これらは、1種単独で使用してもよいし、2種以上を併用してもよい。
前記動物又は魚介類からの抽出エキスの具体例としては、サメ軟骨抽出物(コンドロイチン硫酸)、コラーゲン、ヒアルロン酸などが挙げられる。これらは、1種単独で使用してもよいし、2種以上を併用してもよい。
前記水に溶けにくい原料の具体例としては、ピロリン酸第二鉄、コエンザイムQ10、甘草グラボノイド、5−ロキシンなどが挙げられる。これらは、1種単独で使用してもよいし、2種以上を併用してもよい。
前記崩壊性に劣る原料は、植物、動物、魚介類から調製したものを使用してもよいし、市販品を使用してもよい。
--- Raw material with poor disintegration-
The raw material inferior in disintegrability is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include plant extract extracts, extract extracts from animals or seafood, raw materials that are hardly soluble in water, and glucosamine. These may be used individually by 1 type and may use 2 or more types together.
Specific examples of the plant extract include maca extract, autumn turmeric extract, spring turmeric extract, and guar gum. These may be used individually by 1 type and may use 2 or more types together.
Specific examples of the extract from animals or fish and shellfish include shark cartilage extract (chondroitin sulfate), collagen, hyaluronic acid and the like. These may be used individually by 1 type and may use 2 or more types together.
Specific examples of the raw materials that are hardly soluble in water include ferric pyrophosphate, coenzyme Q10, licorice gravonoid, 5-roxin and the like. These may be used individually by 1 type and may use 2 or more types together.
The raw material inferior in disintegration may be prepared from plants, animals, seafood, or commercially available products.
前記崩壊性に劣る原料の前記混合物における含有量としては、特に制限はなく、目的に応じて適宜選択することができるが、5質量%〜90質量%が好ましく、10質量%〜80質量%がより好ましく、20質量%〜75質量%が特に好ましい。前記含有量が、5質量%未満であると、前記崩壊性に劣る機能性原料の含有量が少ないため、他の賦形剤で代替可能となることがあり、90質量%を超えると、必要な滑沢剤や結合剤を配合できずに錠剤化が難しくなることがある。一方、前記含有量が前記好ましい範囲内であると、十分な錠剤硬度とより早い崩壊時間の両面を併せ持った錠剤を得ることが出来る点で、有利である。 There is no restriction | limiting in particular as content in the said mixture of the raw material inferior to the said disintegration, Although it can select suitably according to the objective, 5 mass%-90 mass% are preferable, and 10 mass%-80 mass% are More preferably, 20% by mass to 75% by mass is particularly preferable. When the content is less than 5% by mass, the content of the functional raw material inferior in disintegration is small, so that it may be possible to substitute with other excipients. It may be difficult to form a tablet without adding a lubricant or binder. On the other hand, when the content is within the preferred range, it is advantageous in that a tablet having both sufficient tablet hardness and faster disintegration time can be obtained.
−−その他の成分−−
前記混合物におけるその他の成分としては、本発明の効果を損なわない限り、特に制限はなく、目的に応じて適宜選択することができ、例えば、前記崩壊性に劣る原料以外の機能性原料(以下、「その他の機能性原料」と称することがある)、滑沢剤、着色剤、pH調整剤、緩衝剤などが挙げられる。これらは、1種単独で使用してもよし、2種以上を併用してもよい。
前記その他の成分の前記混合物における含有量としては、特に制限はなく、目的に応じて適宜選択することができる。
-Other ingredients-
The other components in the mixture are not particularly limited as long as the effects of the present invention are not impaired, and can be appropriately selected depending on the purpose. For example, functional raw materials other than the raw materials inferior in disintegration (hereinafter referred to as the raw materials) (Sometimes referred to as “other functional raw materials”), lubricants, colorants, pH adjusters, buffers, and the like. These may be used alone or in combination of two or more.
There is no restriction | limiting in particular as content in the said mixture of the said other component, According to the objective, it can select suitably.
−−−その他の機能性原料−−−
前記その他の機能性原料としては、特に制限はなく、公知の原料を適宜選択することができ、例えば、アミノ酸又はその塩、ビタミン、ミネラル、ポリフェノールなどが挙げられる。これらは、1種単独で使用してもよし、2種以上を併用してもよい。
前記その他の機能性原料は、市販品を使用することができる。
前記その他の機能性原料の前記混合物における含有量としては、特に制限はなく、目的に応じて適宜選択することができる。
---- Other functional raw materials ---
There is no restriction | limiting in particular as said other functional raw material, A well-known raw material can be selected suitably, For example, an amino acid or its salt, a vitamin, a mineral, polyphenol etc. are mentioned. These may be used alone or in combination of two or more.
Commercially available products can be used as the other functional raw materials.
There is no restriction | limiting in particular as content in the said mixture of the said other functional raw material, According to the objective, it can select suitably.
−−−滑沢剤−−−
前記滑沢剤としては、特に制限はなく、目的に応じて適宜選択することができ、例えば、ステアリン酸、ステアリン酸カルシウム、ステアリン酸マグネシウム、フマル酸ステアリルナトリウム、ショ糖脂肪酸エステル、タルク、微粒二酸化ケイ素、軽質無水ケイ酸、含水二酸化ケイ素、植物油脂、硬化油などが挙げられる。これらは、1種単独で使用してもよし、2種以上を併用してもよい。
前記滑沢剤は、市販品を使用することができる。
前記滑沢剤の前記混合物における含有量としては、特に制限はなく、目的に応じて適宜選択することができる。
---- Lubricant ---
The lubricant is not particularly limited and may be appropriately selected depending on the intended purpose. For example, stearic acid, calcium stearate, magnesium stearate, sodium stearyl fumarate, sucrose fatty acid ester, talc, fine silicon dioxide , Light anhydrous silicic acid, hydrous silicon dioxide, vegetable oil and fat, hydrogenated oil and the like. These may be used alone or in combination of two or more.
A commercially available product can be used as the lubricant.
There is no restriction | limiting in particular as content in the said mixture of the said lubricant, According to the objective, it can select suitably.
−−−着色剤−−−
前記着色剤としては、特に制限はなく、目的に応じて適宜選択することができ、例えば、酸化チタン、酸化鉄、カラメル色素、天然色素などが挙げられる。これらは、1種単独で使用してもよいし、2種以上を併用してもよい。
前記着色剤は、市販品を使用することができる。
前記着色剤の前記混合物における含有量としては、特に制限はなく、目的に応じて適宜選択することができる。
--- Colorant ---
There is no restriction | limiting in particular as said coloring agent, According to the objective, it can select suitably, For example, a titanium oxide, an iron oxide, a caramel pigment | dye, a natural pigment | dye etc. are mentioned. These may be used individually by 1 type and may use 2 or more types together.
A commercially available product can be used as the colorant.
There is no restriction | limiting in particular as content in the said mixture of the said coloring agent, According to the objective, it can select suitably.
−−−pH調整剤、緩衝剤−−−
前記pH調整剤、又は前記緩衝剤としては、特に制限はなく、目的に応じて適宜選択することができ、例えば、クエン酸ナトリウム、酢酸ナトリウム、リン酸ナトリウム、フィチン酸などが挙げられる。これらは、1種単独で使用してもよいし、2種以上を併用してもよい。
前記pH調整剤、又は前記緩衝剤は、市販品を使用することができる。
前記pH調整剤、又は前記緩衝剤の前記混合物における含有量としては、特に制限はなく、目的に応じて適宜選択することができる。
--- pH adjuster, buffer ---
There is no restriction | limiting in particular as said pH adjuster or the said buffering agent, According to the objective, it can select suitably, For example, sodium citrate, sodium acetate, sodium phosphate, phytic acid etc. are mentioned. These may be used individually by 1 type and may use 2 or more types together.
A commercial item can be used for the pH adjuster or the buffer.
There is no restriction | limiting in particular as content in the said mixture of the said pH adjuster or the said buffering agent, According to the objective, it can select suitably.
本発明において、賦形剤、結合剤、及び崩壊剤は、上記した本発明の顆粒を用いることが好ましいが、前記その他の成分として、前記顆粒ではない賦形剤、結合剤、及び崩壊剤の少なくともいずれかが含まれていてもよい。ただし、錠剤における賦形剤、結合剤、及び崩壊剤の少なくともいずれかの量を少なくすることができる点で、前記顆粒ではない賦形剤、結合剤、及び崩壊剤の少なくともいずれかを含まないことが好ましい。 In the present invention, the above-described granules of the present invention are preferably used as the excipient, binder, and disintegrant. However, as the other components, the excipient, binder, and disintegrant that are not the granules are used. At least one of them may be included. However, at least one of excipients, binders, and disintegrants that are not granules is not included in that the amount of excipients, binders, and disintegrants in the tablet can be reduced. It is preferable.
前記混合物の調製方法としては、特に制限はなく、目的に応じて適宜選択することができ、例えば、前記滑沢剤以外の成分を混合した後、その混合物に前記滑沢剤を添加し、混合して調製する方法などが挙げられる。
前記混合の条件としては、特に制限はなく、目的に応じて適宜選択することができる。
The method for preparing the mixture is not particularly limited and may be appropriately selected depending on the purpose. For example, after mixing components other than the lubricant, the lubricant is added to the mixture and mixed. The method of preparing by doing.
There is no restriction | limiting in particular as said mixing conditions, According to the objective, it can select suitably.
−打錠−
前記打錠の方法としては、特に制限はなく、目的に応じて、公知の方法を適宜選択することができる。
前記打錠における打錠圧等の条件としては、特に制限はなく、目的に応じて適宜選択することができる。
-Tableting-
There is no restriction | limiting in particular as the said tableting method, According to the objective, a well-known method can be selected suitably.
There is no restriction | limiting in particular as conditions, such as tableting pressure in the said tableting, According to the objective, it can select suitably.
前記錠剤の形状、大きさ、質量としては、特に制限はなく、目的に応じて適宜選択することができる。
本発明の錠剤の製造方法によれば、前記賦形剤、結合剤、及び崩壊剤の少なくともいずれかとして、前記顆粒を用いるため、圧縮成形性が向上し、また、処方中の賦形剤、結合剤、及び崩壊剤の少なくともいずれかの配合量が少なくても十分な錠剤硬度を担保することができ、かつ崩壊性にも優れるため、摂取しやすい錠剤とすることができる。
例えば、従来、直径8mm、曲率半径(R)12mmとしていた錠剤を直径8mm、曲率半径(R)6.5mmとしたり、直径9mm、曲率半径(R)13mmとしていた錠剤を直径9mm、曲率半径(R)7.5mmとしたりすることができる。また、1錠あたり330mgとしていた錠剤を300mgとしたり、380mgとしていた錠剤を330mgとしたりすることができる。
There is no restriction | limiting in particular as a shape, a magnitude | size, and mass of the said tablet, According to the objective, it can select suitably.
According to the method for producing a tablet of the present invention, since the granule is used as at least one of the excipient, the binder, and the disintegrant, the compression moldability is improved. Even if the blending amount of at least one of the binder and the disintegrant is small, sufficient tablet hardness can be ensured and the disintegration is excellent, so that the tablet can be easily taken.
For example, a tablet having a diameter of 8 mm and a radius of curvature (R) of 12 mm is 8 mm and a radius of curvature (R) of 6.5 mm, or a tablet having a diameter of 9 mm and a radius of curvature (R) of 13 mm is 9 mm and a radius of curvature ( R) can be 7.5 mm. Moreover, the tablet which was 330 mg per tablet can be 300 mg, and the tablet which has been 380 mg can be 330 mg.
<その他の工程>
前記その他の工程としては、本発明の効果を損なわない限り、特に制限はなく、目的に応じて適宜選択することができ、例えば、賦形剤、結合剤、及び崩壊剤の少なくともいずれかを含む液体を調製する工程などが挙げられる。
前記賦形剤、結合剤、及び崩壊剤の少なくともいずれかを含む液体を調製する方法としては、特に制限はなく、目的に応じて適宜選択することができ、例えば、水、温水、又はエタノールを含む水溶液に、前記賦形剤、結合剤、及び崩壊剤の少なくともいずれかを溶解させる方法などが挙げられる。
<Other processes>
The other steps are not particularly limited as long as the effects of the present invention are not impaired, and can be appropriately selected depending on the purpose, and include, for example, at least one of an excipient, a binder, and a disintegrant. Examples include a step of preparing a liquid.
A method for preparing a liquid containing at least one of the above-mentioned excipient, binder, and disintegrant is not particularly limited and can be appropriately selected depending on the purpose. For example, water, hot water, or ethanol is used. Examples include a method of dissolving at least one of the excipient, the binder, and the disintegrant in the aqueous solution.
本発明の錠剤の製造方法によれば、崩壊性に劣る原料を含む錠剤であっても、十分な錠剤硬度を得ることができ、かつ崩壊性に優れた錠剤を簡易に効率良く製造することができる。 According to the method for producing a tablet of the present invention, it is possible to easily and efficiently produce a tablet having a sufficient disintegration property and capable of obtaining a sufficient tablet hardness even for a tablet containing a raw material that is inferior in disintegration. it can.
(錠剤原料用顆粒及びその製造方法)
本発明の錠剤原料用顆粒は、本発明の錠剤原料用顆粒の製造方法により好適に製造することができる。
以下、本発明の錠剤原料用顆粒の製造方法の説明と併せて、本発明の錠剤原料用顆粒についても説明する。
(Tablet granule and method for producing the same)
The granule for tablet raw material of this invention can be suitably manufactured with the manufacturing method of the granule for tablet raw material of this invention.
Hereinafter, the granule for tablet raw material of this invention is also demonstrated with description of the manufacturing method of the granule for tablet raw material of this invention.
<錠剤原料用顆粒の製造方法>
本発明の錠剤原料用顆粒の製造方法は、錠剤原料用の賦形剤、結合剤、及び崩壊剤の少なくともいずれかの顆粒の製造方法であって、ガス含有液体調製工程と、顆粒調製工程とを少なくとも含み、必要に応じて更にその他の工程を含む。
<Method for producing granules for tablet material>
The method for producing granules for tablet raw material according to the present invention is a method for producing granules of at least one of excipients, binders, and disintegrants for tablet raw materials, comprising a gas-containing liquid preparation step, a granule preparation step, And at least other steps as necessary.
<<ガス含有液体調製工程>>
前記ガス含有液体調製工程は、上記した本発明の錠剤の製造方法におけるガス含有液体調製工程の項目に記載したものと同様である。
<< Gas-containing liquid preparation process >>
The gas-containing liquid preparation step is the same as that described in the item of the gas-containing liquid preparation step in the tablet production method of the present invention described above.
<<顆粒調製工程>>
前記顆粒調製工程は、上記した本発明の錠剤の製造方法における顆粒調製工程の項目に記載したものと同様である。
<< Granule preparation process >>
The granule preparation step is the same as that described in the item of the granule preparation step in the tablet production method of the present invention described above.
<<その他の工程>>
前記その他の工程としては、本発明の効果を損なわない限り、特に制限はなく、目的に応じて適宜選択することができ、例えば、上記した本発明の錠剤の製造方法におけるその他の工程の項目に記載したものと同様のものなどが挙げられる。
<< Other processes >>
The other steps are not particularly limited as long as the effects of the present invention are not impaired, and can be appropriately selected according to the purpose. For example, the other steps in the above-described method for producing a tablet of the present invention The thing similar to what was described is mentioned.
本発明の錠剤原料用顆粒の製造方法によれば、十分な錠剤硬度を有し、かつ崩壊性に優れた錠剤の製造に好適に用いることができる顆粒を簡易に効率良く製造することができる。 According to the method for producing a granule for tablet raw material of the present invention, a granule that can be suitably used for producing a tablet having sufficient tablet hardness and excellent disintegration can be produced easily and efficiently.
<錠剤原料用顆粒>
本発明の錠剤原料用顆粒は、錠剤原料用の賦形剤、結合剤、及び崩壊剤の少なくともいずれかの顆粒であって、空隙を有する多孔質な顆粒である。
<Tablet granules>
The granule for tablet raw material of the present invention is a granule of at least one of an excipient, a binder, and a disintegrant for tablet raw material, and is a porous granule having voids.
−かさ密度−
前記錠剤用顆粒のかさ密度としては、顆粒とする前の原料のかさ密度の40%〜90%であれば、特に制限はなく、目的に応じて適宜選択することができるが、45%〜80%がより好ましい。
前記かさ密度とは、ゆるめかさ密度をいう。
前記かさ密度の測定装置としては、特に制限はなく、公知の装置を適宜選択することができ、例えば、レーザー回折・散乱式 粒子径・粒度分布測定装置 マイクロトラックMT3000II(日機装株式会社製)などが挙げられる。
-Bulk density-
The bulk density of the granule for tablets is not particularly limited as long as it is 40% to 90% of the bulk density of the raw material before granulation, and can be appropriately selected according to the purpose. % Is more preferable.
The bulk density refers to a loose bulk density.
The bulk density measuring device is not particularly limited, and a known device can be appropriately selected. For example, a laser diffraction / scattering type particle diameter / particle size distribution measuring device Microtrac MT3000II (manufactured by Nikkiso Co., Ltd.) can be used. Can be mentioned.
−メディアン径(D50)−
前記錠剤用顆粒のメディアン径としては、140μm〜240μmであれば、特に制限はなく、目的に応じて適宜選択することができるが、150μm〜205μmがより好ましい。
前記メディアン径の測定装置としては、特に制限はなく、公知の装置を適宜選択することができ、例えば、レーザー回折・散乱式 粒子径・粒度分布測定装置 マイクロトラックMT3000II(日機装株式会社製)などが挙げられる。
-Median diameter (D50)-
The median diameter of the tablet granule is not particularly limited as long as it is 140 μm to 240 μm, and can be appropriately selected according to the purpose, but 150 μm to 205 μm is more preferable.
The median diameter measuring device is not particularly limited, and a known device can be appropriately selected. For example, a laser diffraction / scattering particle size / particle size distribution measuring device Microtrac MT3000II (manufactured by Nikkiso Co., Ltd.) can be used. Can be mentioned.
以下に試験例を挙げて本発明を具体的に説明するが、本発明はこれらの試験例に何ら限定されるものではない。 The present invention will be specifically described below with reference to test examples, but the present invention is not limited to these test examples.
(試験例1−1〜1−3)
崩壊性に劣る原料として、コンドロイチン硫酸(サメ軟骨抽出物)を用い、以下のようにして錠剤を製造した。
−打錠末の調製−
以下の配合処方のうち、ステアリン酸カルシウム以外を混合した後、その混合物にステアリン酸カルシウムを添加し、混合して、打錠末とした。
〔配合処方:試験例1−1〕
・ サメ軟骨抽出物 ・・・ 71.4質量%
(サメ軟骨由来食品用コンドロイチン−70、上海輝文生物技術有限公司社製)
・ 結晶セルロース・微粒酸化ケイ素 ・・・ 27.6質量%
(NUTRASOLV 90F、JRS Pharma社製)
・ ステアリン酸カルシウム ・・・ 1.0質量%
(堺化学工業株式会社製;滑沢剤)
〔配合処方:試験例1−2〕
・ サメ軟骨抽出物 ・・・ 71.4質量%
(サメ軟骨由来食品用コンドロイチン−70、上海輝文生物技術有限公司社製)
・ 結晶セルロース・微粒酸化ケイ素 ・・・ 22.6質量%
(NUTRASOLV 90F、JRS Pharma社製)
・ 崩壊剤 ・・・ 5.0質量%
(部分α化デンプンPCS、旭化成ケミカルズ株式会社社製)
・ ステアリン酸カルシウム ・・・ 1.0質量%
(堺化学工業株式会社製;滑沢剤)
〔配合処方:試験例1−3〕
・ サメ軟骨抽出物 ・・・ 71.6質量%
(サメ軟骨由来食品用コンドロイチン−70、上海輝文生物技術有限公司社製)
・ 結晶セルロース・微粒酸化ケイ素 ・・・ 25.6質量%
(NUTRASOLV 90F、JRS Pharma社製)
・ 崩壊剤 ・・・ 2.0質量%
(explotab、JRS Pharma社製)
・ ステアリン酸カルシウム ・・・ 1.0質量%
(堺化学工業株式会社製;滑沢剤)
(Test Examples 1-1 to 1-3)
Chondroitin sulfate (shark cartilage extract) was used as a raw material inferior in disintegration, and tablets were produced as follows.
-Preparation of tableting powder-
Of the following blended prescriptions, other than calcium stearate was mixed, and then calcium stearate was added to the mixture and mixed to obtain a tableting powder.
[Formulation prescription: Test example 1-1]
・ Shark cartilage extract: 71.4% by mass
(Shark cartilage-derived food chondroitin-70, manufactured by Shanghai Huifeng Biological Technology Co., Ltd.)
・ Crystalline cellulose ・ fine silicon oxide ・ ・ ・ 27.6 mass%
(NUTRASOLV 90F, manufactured by JRS Pharma)
・ Calcium stearate: 1.0% by mass
(Manufactured by Sakai Chemical Industry Co., Ltd .; lubricant)
[Formulation prescription: Test example 1-2]
・ Shark cartilage extract: 71.4% by mass
(Shark cartilage-derived food chondroitin-70, manufactured by Shanghai Huifeng Biological Technology Co., Ltd.)
・ Crystalline cellulose ・ fine silicon oxide ・ ・ ・ 22.6 mass%
(NUTRASOLV 90F, manufactured by JRS Pharma)
・ Disintegrant: 5.0% by mass
(Partial pregelatinized starch PCS, manufactured by Asahi Kasei Chemicals Corporation)
・ Calcium stearate: 1.0% by mass
(Manufactured by Sakai Chemical Industry Co., Ltd .; lubricant)
[Composition formula: Test example 1-3]
・ Shark cartilage extract ... 71.6% by mass
(Shark cartilage-derived food chondroitin-70, manufactured by Shanghai Huifeng Biological Technology Co., Ltd.)
・ Crystalline cellulose ・ fine silicon oxide ・ ・ ・ 25.6% by mass
(NUTRASOLV 90F, manufactured by JRS Pharma)
・ Disintegrant ... 2.0% by mass
(Explotab, manufactured by JRS Pharma)
・ Calcium stearate: 1.0% by mass
(Manufactured by Sakai Chemical Industry Co., Ltd .; lubricant)
−打錠−
ロータリー打錠機(HATA AP−12SS、株式会社畑鉄工所製)を用い、以下の条件で打錠加工し、錠剤を製造した。
〔打錠条件〕
・ 杵立数 : 6本
・ 使用杵 : 硬質クロムメッキ処理がされた杵(標準的に使用されている杵)
・ 回転数 : 40rpm
・ 打錠圧 : 8kN、13kN、又は15kN
・ 剤形 : 直径9mm、曲率半径(R)7.5mm
・ 錠剤質量 : 300mg
-Tableting-
Using a rotary tableting machine (HATA AP-12SS, manufactured by Hata Iron Works Co., Ltd.), tableting was performed under the following conditions to produce tablets.
[Tabletting conditions]
・ Number of ridges: 6 ・ Used 杵: Hard chrome-plated heel (standard heel)
・ Number of revolutions: 40 rpm
・ Tableting pressure: 8kN, 13kN, or 15kN
・ Dosage form: Diameter 9mm, radius of curvature (R) 7.5mm
・ Tablet mass: 300mg
<評価:錠剤硬度>
前記試験例1−1〜1−3の錠剤の硬度を、錠剤破壊強度測定器TH−303MP(富山産業株式会社製)を用いて測定した。結果を表1に示す。
<Evaluation: Tablet hardness>
The hardness of the tablets of Test Examples 1-1 to 1-3 was measured using a tablet breaking strength meter TH-303MP (manufactured by Toyama Sangyo Co., Ltd.). The results are shown in Table 1.
<評価:崩壊時間>
前記試験例1−1〜1−3の錠剤の崩壊時間を、日本薬局方第16改正に記載されている崩壊試験法により測定した。結果を表1に示す。
<Evaluation: Collapse time>
The disintegration time of the tablets of Examples 1-1 to 1-3 was measured by the disintegration test method described in the 16th revision of the Japanese Pharmacopoeia. The results are shown in Table 1.
表1の結果から、崩壊剤を含有する試験例1−2及び1−3の錠剤は、試験例1−1の錠剤と比較して、崩壊時間が若干短くなったものの十分とは言えず、また、錠剤硬度が低下してしまうことが確認された。
したがって、崩壊性に劣る原料を含む錠剤に崩壊剤を添加しても、崩壊時間を十分短くすることはできず、また、錠剤硬度も低下してしまい、圧縮成形性が劣ることが示された。
From the results of Table 1, the tablets of Test Examples 1-2 and 1-3 containing a disintegrant were not sufficient, although the disintegration time was slightly shorter than the tablets of Test Example 1-1. Moreover, it was confirmed that tablet hardness will fall.
Therefore, even when a disintegrant is added to a tablet containing a raw material that is inferior in disintegrability, the disintegration time cannot be shortened sufficiently, and the tablet hardness also decreases, indicating that the compression moldability is inferior. .
(試験例2−1〜2−5)
崩壊性に劣る原料として、コンドロイチン硫酸(サメ軟骨抽出物)を用い、賦形剤として、パインデックス#100(澱粉分解物)を用い、以下のようにして、錠剤を製造した。
<賦形剤含有液体の調製>
パインデックス#100(松谷化学工業株式会社製)を水に溶解させ、パインデックス#100の含有量が、30質量%の賦形剤含有液体とした。
(Test Examples 2-1 to 2-5)
Tablets were produced as follows using chondroitin sulfate (shark cartilage extract) as a raw material inferior in disintegrability and using paindex # 100 (starch decomposed product) as an excipient.
<Preparation of excipient-containing liquid>
Paindex # 100 (manufactured by Matsutani Chemical Industry Co., Ltd.) was dissolved in water to obtain an excipient-containing liquid in which the content of Paindex # 100 was 30% by mass.
<ガス含有液体の調製、及び顆粒の調製>
噴霧乾燥装置(MicraSpray750(Anhydro社製))及びガス注入装置(ADS(Anhydro社製))を用い、以下の条件で、噴霧手前の前記賦形剤含有液体に窒素ガスを注入し、その後、前記窒素ガスを注入した賦形剤含有液体を以下の条件で、噴霧乾燥し、顆粒を得た。
−ガス注入条件−
・ ガス注入量 : 0mL/分(試験例2−1)、5,000mL/分(試験例2−2)、10,000mL/分/分(試験例2−3)、15,000mL/分(試験例2−4)
・ 賦形剤含有液体の送液量 : 333mL/分〜383mL/分
<Preparation of gas-containing liquid and preparation of granules>
Using a spray drying device (MicraSpray750 (manufactured by Anhydro)) and a gas injection device (ADS (manufactured by Anhydro)), nitrogen gas was injected into the excipient-containing liquid before spraying under the following conditions, and then The excipient-containing liquid into which nitrogen gas was injected was spray-dried under the following conditions to obtain granules.
-Gas injection conditions-
-Gas injection amount: 0 mL / min (Test Example 2-1), 5,000 mL / min (Test Example 2-2), 10,000 mL / min / min (Test Example 2-3), 15,000 mL / min ( Test Example 2-4)
-Amount of liquid containing excipient: 333 mL / min to 383 mL / min
−噴霧乾燥条件−
窒素ガスを注入した固形分30質量%の賦形剤含有液体を送液量333mL/分〜383mL/分、熱風温度165℃〜170℃、排風温度86℃〜87℃の条件下で噴霧乾燥を行った。
-Spray drying conditions-
Spray-dried an excipient-containing liquid with a solid content of 30% by mass injecting nitrogen gas under the conditions of a feed rate of 333 mL / min to 383 mL / min, a hot air temperature of 165 ° C. to 170 ° C., and an exhaust air temperature of 86 ° C. to 87 ° C. Went.
<錠剤の調製>
前記試験例2−1〜2−4の顆粒、又はコントロールとして、噴霧乾燥を行っていないパインデックス#100(試験例2−5)を用い、以下のようにして、試験例2−1〜2−5の錠剤を調製した。
−打錠末の調製−
以下の配合処方の原料のうち、ステアリン酸カルシウム以外を混合した後、その混合物にステアリン酸カルシウムを添加し、混合して、打錠末とした。
〔配合処方〕
・ サメ軟骨抽出物 ・・・ 71.4質量%
(サメ軟骨由来食品用コンドロイチン−70、上海輝文生物技術有限公司社製)
・ 賦形剤 ・・・ 27.6質量%
(試験例2−1〜2−4の顆粒、又は噴霧乾燥を行っていないパインデックス#100)
・ ステアリン酸カルシウム ・・・ 1.0質量%
(堺化学工業株式会社製;滑沢剤)
<Preparation of tablets>
Test Example 2-1 to 2 were used as follows, using Granules of Test Examples 2-1 to 2-4, or Paindex # 100 (Test Example 2-5) that was not spray-dried as a control. -5 tablets were prepared.
-Preparation of tableting powder-
Among the raw materials of the following formulation, after mixing other than calcium stearate, calcium stearate was added to the mixture and mixed to obtain a tableting powder.
[Prescription]
・ Shark cartilage extract: 71.4% by mass
(Shark cartilage-derived food chondroitin-70, manufactured by Shanghai Huifeng Biological Technology Co., Ltd.)
・ Excipient: 27.6% by mass
(Granules of Test Examples 2-1 to 2-4, or Paindex # 100 which is not spray-dried)
・ Calcium stearate: 1.0% by mass
(Manufactured by Sakai Chemical Industry Co., Ltd .; lubricant)
−打錠−
ロータリー打錠機(HATA AP−12SS、株式会社畑鉄工所製)を用い、以下の条件で打錠加工し、錠剤を製造した。
〔打錠条件〕
・ 杵立数 : 6本
・ 使用杵 : 硬質クロムメッキ処理がされた杵(標準的に使用されている杵)
・ 回転数 : 40rpm
・ 打錠圧 : 8kN、13kN、又は15kN
・ 剤形 : 直径9mm、曲率半径(R)7.5mm
・ 錠剤質量 : 300mg
-Tableting-
Using a rotary tableting machine (HATA AP-12SS, manufactured by Hata Iron Works Co., Ltd.), tableting was performed under the following conditions to produce tablets.
[Tabletting conditions]
・ Number of ridges: 6 ・ Used 杵: Hard chrome-plated heel (standard heel)
・ Number of revolutions: 40 rpm
・ Tableting pressure: 8kN, 13kN, or 15kN
・ Dosage form: Diameter 9mm, radius of curvature (R) 7.5mm
・ Tablet mass: 300mg
<評価:錠剤硬度>
前記試験例2−1〜2−5の錠剤の硬度を、錠剤破壊強度測定器TH−303MP(富山産業株式会社製)を用いて測定した。結果を試験例1−1の結果と共に表2−1に示す。
<Evaluation: Tablet hardness>
The hardness of the tablets of Test Examples 2-1 to 2-5 was measured using a tablet breaking strength meter TH-303MP (manufactured by Toyama Sangyo Co., Ltd.). The results are shown in Table 2-1 together with the results of Test Example 1-1.
<評価:崩壊時間>
前記試験例2−1〜2−5の錠剤の崩壊時間を、日本薬局方第16改正に記載されている崩壊試験法により測定した。結果を試験例1−1の結果と共に表2−1に示す。
<Evaluation: Collapse time>
The disintegration time of the tablets of Test Examples 2-1 to 2-5 was measured by the disintegration test method described in Japanese Pharmacopoeia 16th revision. The results are shown in Table 2-1 together with the results of Test Example 1-1.
表2−1の結果から、ガスを注入し、噴霧乾燥を行った試験例2−2〜2−4では、十分な錠剤硬度が得られた。また、ガスの注入量を上げることによって、錠剤硬度が、試験例1−1と同等程度まで上昇した。 From the results of Table 2-1, sufficient tablet hardness was obtained in Test Examples 2-2 to 2-4 in which gas was injected and spray drying was performed. Moreover, tablet hardness rose to the same level as test example 1-1 by raising the injection amount of gas.
通常、錠剤硬度が上昇した場合、崩壊時間もそれに伴い伸びることが知られており、表2−1の結果から、試験例1−1の錠剤では、低打錠圧のものでも崩壊時間が長く、また、打錠圧が高くなるにつれて崩壊時間は延びていた。一方、試験例2−2〜2−4の錠剤は、試験例2−1及び2−5の錠剤よりも錠剤硬度が上がっていたにも関わらず、崩壊時間が試験例1−1よりも短くなっていた。 Usually, it is known that when the tablet hardness is increased, the disintegration time is increased accordingly, and from the results shown in Table 2-1, the disintegration time is long for the tablets of Test Example 1-1 even when the tableting pressure is low. In addition, the disintegration time increased as the tableting pressure increased. On the other hand, the tablets of Test Examples 2-2 to 2-4 were shorter in disintegration time than Test Example 1-1 although the tablet hardness was higher than that of Test Examples 2-1 and 2-5. It was.
上記結果から、ガスを注入した賦形剤含有液体を噴霧乾燥することにより得られた顆粒を用いることで、崩壊性に劣る原料を含む錠剤の錠剤硬度及び崩壊性が改善されることが示された。 The above results show that tablet hardness and disintegration of tablets containing raw materials that are inferior in disintegration can be improved by using granules obtained by spray-drying an excipient-containing liquid into which gas has been injected. It was.
<評価:顆粒>
前記試験例2−1〜2−4で得られた顆粒と、試験例2−5で用いた噴霧乾燥を行っていないパインデックス#100について、レーザー回折・散乱式 粒子径・粒度分布測定装置 マイクロトラックMT3000II(日機装株式会社製)により、ゆるめかさ密度、メディアン径(D50)を測定した。結果を表2−2に示す。
また、電子顕微鏡(日立卓上顕微鏡Miniacope TM3000、株式会社日立ハイテクノロジーズ社製)により、各顆粒を観察した。結果を図1A〜図1Dに示す。
<Evaluation: Granule>
For the granules obtained in Test Examples 2-1 to 2-4 and Paindex # 100 used in Test Example 2-5 that has not been spray-dried, a laser diffraction / scattering particle size / particle size distribution measuring device Micro Loose bulk density and median diameter (D50) were measured with a truck MT3000II (manufactured by Nikkiso Co., Ltd.). The results are shown in Table 2-2.
Moreover, each granule was observed with the electron microscope (Hitachi desktop microscope Miniacop TM3000, Hitachi High-Technologies Corporation make). The results are shown in FIGS. 1A to 1D.
図1Aは、試験例2−1で得られた顆粒の観察結果の一例を示し、図1Bは、試験例2−2で得られた顆粒の観察結果の一例を示し、図1Cは、試験例2−3で得られた顆粒の観察結果の一例を示し、図1Dは、試験例2−4で得られた顆粒の観察結果の一例を示す。 1A shows an example of the observation result of the granule obtained in Test Example 2-1, FIG. 1B shows an example of the observation result of the granule obtained in Test Example 2-2, and FIG. 1C shows the test example. An example of the observation result of the granule obtained in 2-3 is shown, and FIG. 1D shows an example of the observation result of the granule obtained in Test Example 2-4.
表2−2、及び図1A〜図1Dの結果から、ガスを注入した賦形剤含有液体を噴霧乾燥することにより得られた顆粒は、空隙を有する多孔質な顆粒となっていることが確認された。 From the results of Table 2-2 and FIGS. 1A to 1D, it was confirmed that the granules obtained by spray drying the excipient-containing liquid into which the gas was injected were porous granules having voids. It was done.
(試験例3−1〜3−4)
崩壊性に劣る原料として、コンドロイチン硫酸(サメ軟骨抽出物)を用い、結合剤として、グアーガムを用い、以下のようにして、錠剤を製造した。
<結合剤含有液体の調製>
グアーガム(グアーガムHS、太陽化学株式会社製)を水に溶解させ、グアーガムの含有量が、30質量%の結合剤含有液体とした。
(Test Examples 3-1 to 3-4)
Using chondroitin sulfate (shark cartilage extract) as a raw material inferior in disintegrability and guar gum as a binder, tablets were produced as follows.
<Preparation of binder-containing liquid>
Guar gum (Guar gum HS, manufactured by Taiyo Kagaku Co., Ltd.) was dissolved in water to obtain a binder-containing liquid having a guar gum content of 30% by mass.
<ガス含有液体の調製、及び顆粒の調製>
噴霧乾燥装置(MicraSpray750(Anhydro社製))及びガス注入装置(ADS(Anhydro社製))を用い、以下の条件で、噴霧手前の前記賦形剤含有液体に窒素ガスを注入し、その後、前記窒素ガスを注入した結合剤含有液体を以下の条件で、噴霧乾燥し、顆粒を得た。
−ガス注入条件−
・ ガス注入量 : 0mL/分(試験例3−1)、10,000mL/分(試験例3−2)、15,000mL/分(試験例3−3)
・ 結合剤含有液体の送液量 : 333mL/分〜383mL/分
<Preparation of gas-containing liquid and preparation of granules>
Using a spray drying device (MicraSpray750 (manufactured by Anhydro)) and a gas injection device (ADS (manufactured by Anhydro)), nitrogen gas was injected into the excipient-containing liquid before spraying under the following conditions, and then The binder-containing liquid into which nitrogen gas was injected was spray-dried under the following conditions to obtain granules.
-Gas injection conditions-
-Gas injection amount: 0 mL / min (Test Example 3-1), 10,000 mL / min (Test Example 3-2), 15,000 mL / min (Test Example 3-3)
・ Amount of liquid containing binder: 333 mL / min to 383 mL / min
−噴霧乾燥条件−
窒素ガスを注入した固形分30質量%の結合剤含有液体を送液量333mL/分〜383mL/分、熱風温度165℃〜170℃、排風温度86℃〜87℃の条件下で噴霧乾燥を行った。
-Spray drying conditions-
Binder-containing liquid with a solid content of 30% by mass injecting nitrogen gas is spray-dried under conditions of a feed rate of 333 mL / min to 383 mL / min, hot air temperature of 165 ° C. to 170 ° C., and exhaust air temperature of 86 ° C. to 87 ° C. went.
<錠剤の調製>
前記試験例3−1〜3−3の顆粒、又はコントロールとして、噴霧乾燥を行っていないグアーガム(グアーガムHS、太陽化学株式会社製、試験例3−4)を用い、以下のようにして、試験例3−1〜3−4の錠剤を調製した。
−打錠末の調製−
以下の配合処方の原料のうち、ステアリン酸カルシウム以外を混合した後、その混合物にステアリン酸カルシウムを添加し、混合して、打錠末とした。
〔配合処方〕
・ サメ軟骨抽出物 ・・・ 71.4質量%
(サメ軟骨由来食品用コンドロイチン−70、上海輝文生物技術有限公司社製)
・ 結合剤 ・・・ 27.6質量%
(試験例3−1〜3−3の顆粒、又は噴霧乾燥を行っていないグアーガムHS)
・ ステアリン酸カルシウム ・・・ 1.0質量%
(堺化学工業株式会社製;滑沢剤)
<Preparation of tablets>
Using guar gum (Guar Gum HS, manufactured by Taiyo Kagaku Co., Ltd., Test Example 3-4) that has not been spray-dried as granules of Test Examples 3-1 to 3-3, or as a control, the test was performed as follows. The tablets of Examples 3-1 to 3-4 were prepared.
-Preparation of tableting powder-
Among the raw materials of the following formulation, after mixing other than calcium stearate, calcium stearate was added to the mixture and mixed to obtain a tableting powder.
[Prescription]
・ Shark cartilage extract: 71.4% by mass
(Shark cartilage-derived food chondroitin-70, manufactured by Shanghai Huifeng Biological Technology Co., Ltd.)
・ Binder ... 27.6 mass%
(Gran gum HS not subjected to granulation of Test Examples 3-1 to 3-3 or spray drying)
・ Calcium stearate: 1.0% by mass
(Manufactured by Sakai Chemical Industry Co., Ltd .; lubricant)
−打錠−
ロータリー打錠機(HATA AP−12SS、株式会社畑鉄工所製)を用い、以下の条件で打錠加工し、錠剤を製造した。
〔打錠条件〕
・ 杵立数 : 6本
・ 使用杵 : 硬質クロムメッキ処理がされた杵(標準的に使用されている杵)
・ 回転数 : 40rpm
・ 打錠圧 : 6kN、10kN、14kN、又は18kN
・ 剤形 : 直径9mm、曲率半径(R)7.5mm
・ 錠剤質量 : 300mg
-Tableting-
Using a rotary tableting machine (HATA AP-12SS, manufactured by Hata Iron Works Co., Ltd.), tableting was performed under the following conditions to produce tablets.
[Tabletting conditions]
・ Number of ridges: 6 ・ Used 杵: Hard chrome-plated heel (standard heel)
・ Number of revolutions: 40 rpm
・ Tableting pressure: 6kN, 10kN, 14kN, or 18kN
・ Dosage form: Diameter 9mm, radius of curvature (R) 7.5mm
・ Tablet mass: 300mg
<評価:錠剤硬度>
前記試験例3−1〜3−4の錠剤の硬度を、錠剤破壊強度測定器TH−303MP(富山産業株式会社製)を用いて測定した。結果を表3−1に示す。
<Evaluation: Tablet hardness>
The hardness of the tablets of Test Examples 3-1 to 3-4 was measured using a tablet breaking strength meter TH-303MP (manufactured by Toyama Sangyo Co., Ltd.). The results are shown in Table 3-1.
<評価:崩壊時間>
前記試験例3−1〜3−4の錠剤の崩壊時間を、日本薬局方第16改正に記載されている崩壊試験法により測定した。結果を表3−1に示す。
<Evaluation: Collapse time>
The disintegration time of the tablets of Test Examples 3-1 to 3-4 was measured by the disintegration test method described in Japanese Pharmacopoeia 16th revision. The results are shown in Table 3-1.
表3−1の結果から、ガスを注入し、噴霧乾燥を行った試験例3−2〜3−3では、試験例3−1及び3−4と比較して高い錠剤硬度が得られた。また、同じ錠剤硬度で比較すると、試験例3−2〜3−3で得られた錠剤の崩壊性は、試験例3−1及び3−4で得られた錠剤よりも優れていることが確認された。 From the results of Table 3-1, in Test Examples 3-2 to 3-3 in which gas was injected and spray drying was performed, a higher tablet hardness was obtained compared to Test Examples 3-1 and 3-4. Moreover, when compared with the same tablet hardness, it was confirmed that the disintegration properties of the tablets obtained in Test Examples 3-2 to 3-3 were superior to the tablets obtained in Test Examples 3-1 and 3-4. It was done.
上記結果から、ガスを注入した結合剤含有液体を噴霧乾燥することにより得られた顆粒を用いることで、崩壊性に劣る原料を含む錠剤の錠剤硬度及び崩壊性が改善されることが示された。 From the above results, it was shown that tablet hardness and disintegration of tablets containing raw materials inferior in disintegration can be improved by using granules obtained by spray drying a binder-containing liquid into which gas has been injected. .
<評価:顆粒>
前記試験例3−1〜3−3で得られた顆粒と、試験例3−4で用いた噴霧乾燥を行っていないグアーガムHSについて、レーザー回折・散乱式 粒子径・粒度分布測定装置 マイクロトラックMT3000II(日機装株式会社製)により、ゆるめかさ密度、メディアン径(D50)を測定した。結果を表3−2に示す。
また、電子顕微鏡(日立卓上顕微鏡Miniacope TM3000、株式会社日立ハイテクノロジーズ社製)により、各顆粒を観察した。結果を図2A〜図2Cに示す。
<Evaluation: Granule>
For the granules obtained in Test Examples 3-1 to 3-3 and the guar gum HS that was not spray-dried used in Test Example 3-4, a laser diffraction / scattering type particle diameter / particle size distribution measuring device Microtrac MT3000II The loose bulk density and median diameter (D50) were measured by Nikkiso Co., Ltd. The results are shown in Table 3-2.
Moreover, each granule was observed with the electron microscope (Hitachi desktop microscope Miniacop TM3000, Hitachi High-Technologies Corporation make). The results are shown in FIGS. 2A to 2C.
図2Aは、試験例3−1で得られた顆粒の観察結果の一例を示し、図2Bは、試験例3−2で得られた顆粒の観察結果の一例を示し、図2Cは、試験例3−3で得られた顆粒の観察結果の一例を示す。 2A shows an example of the observation result of the granule obtained in Test Example 3-1, FIG. 2B shows an example of the observation result of the granule obtained in Test Example 3-2, and FIG. 2C shows the test example. An example of the observation result of the granule obtained in 3-3 is shown.
表3−2、及び図2A〜図2Cの結果から、ガスを注入した賦形剤含有液体を噴霧乾燥することにより得られた顆粒は、空隙を有する多孔質な顆粒となっていることが確認された。 From the results of Table 3-2 and FIGS. 2A to 2C, it was confirmed that the granules obtained by spray drying the excipient-containing liquid into which the gas was injected were porous granules having voids. It was done.
以上の結果から、本願発明の顆粒を打錠(圧縮成形)すると、原料自体が可塑変形を起こすことで原料同士が結合しやすくなり、原料の圧縮成形性が上昇し、十分な錠剤硬度を示し、且つ崩壊性に優れた錠剤を製造できると考えられる。
そのため、前記顆粒を用いることによって、これまで多く配合する必要があった賦形剤、崩壊剤、結合剤の配合量を減らすことができるため、錠剤の小粒化や、1日目安粒数が多い場合は、粒数の削減が可能となる。
また、本発明の錠剤の製造方法によれば、十分な錠剤硬度を示し、且つ崩壊性に優れた錠剤を簡易に、効率良く製造することができる。
From the above results, when the granules of the present invention are tableted (compressed), the raw materials themselves are easily deformed by plastic deformation, the raw materials are easily bonded to each other, and the compression molding properties of the raw materials are increased, thereby showing sufficient tablet hardness. In addition, it is considered that a tablet excellent in disintegration can be produced.
Therefore, by using the granules, the amount of excipients, disintegrants, and binders that have been required to be added in a large amount can be reduced. In this case, the number of grains can be reduced.
Moreover, according to the tablet manufacturing method of the present invention, it is possible to easily and efficiently manufacture a tablet exhibiting sufficient tablet hardness and excellent disintegration.
Claims (7)
前記ガス含有液体を噴霧乾燥し、顆粒を調製する工程と、
前記顆粒と、崩壊性に劣る原料とを含む混合物を打錠し、錠剤を調製する工程とを含むことを特徴とする錠剤の製造方法。 Injecting a gas into a liquid containing at least one of an excipient, a binder, and a disintegrant to prepare a gas-containing liquid;
Spray-drying the gas-containing liquid to prepare granules;
The tablet manufacturing method characterized by including the process of tableting the mixture containing the said granule and the raw material inferior in disintegration, and preparing a tablet.
賦形剤、結合剤、及び崩壊剤の少なくともいずれかを含む液体にガスを注入し、ガス含有液体を調製する工程と、
前記ガス含有液体を噴霧乾燥し、顆粒を調製する工程とを含むことを特徴とする錠剤原料用顆粒の製造方法。 A method for producing granules of at least one of excipients, binders, and disintegrants for tablet raw materials,
Injecting a gas into a liquid containing at least one of an excipient, a binder, and a disintegrant to prepare a gas-containing liquid;
And a step of spray-drying the gas-containing liquid to prepare granules.
前記顆粒のかさ密度が、顆粒とする前の原料のかさ密度の40%〜90%であり、
前記顆粒のメディアン径が、140μm〜240μmであることを特徴とする錠剤原料用顆粒。 Granules for at least one of excipients, binders, and disintegrants for tablet raw materials,
The bulk density of the granules is 40% to 90% of the bulk density of the raw material before the granules,
Granules for tablet raw materials, wherein the granule has a median diameter of 140 μm to 240 μm.
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