The tablet of the present invention is a tablet containing a compression-sensitive drug, has high hardness, can suppress the generation of related substances even by using a direct tableting method, and can stably generate related substances even after long-term storage. It has the effect that it can suppress.
Details of the present invention will be described below, but the scope of the present invention is not limited thereto.
The tablet of the present invention contains a pressure sensitive drug.
The impact-sensitive drug refers to a drug in which, when a raw material powder containing a medicinal ingredient is compression-molded to form a tablet, the medicinal ingredient is decomposed and related substances increase with an increase in compression molding pressure. Specifically, as shown in Test Example 1, when the tableting tablet is subjected to a storage stability test by changing the tableting pressure at the time of tableting, it is a drug that accumulates related substances as the tableting pressure increases.
A related substance is an impurity in a drug product manufactured using a drug substance manufactured by a chemical synthesis method, or a reaction product of a drug substance decomposition product or drug substance with a pharmaceutical additive or a direct container / capping system. Refers to the product.
Representative impact-sensitive drugs include candesartan cilexetil, N- (2-hydroxyethyl) nicotinic acid amide nitrate, (E) -1- [4- (2-diamino) ethoxy] phenyl-2- (4 -Isopropylphenyl) -1- (4-phosphonooxy) phenyl-1-butene, 5,6,7,8-tetrahydro-3- (5-methoxy-1,3,4-oxadiazol-2-yl)- 6-benzyl-1, 6-naphthyridin-2 (1H) -one (SX-3228) and the like.
Among these, among the heat, light, moisture, reactivity with excipients, reactivity between drugs, and impact pressure listed as the cause of generation of related substances, candesartan silylate is a drug that is susceptible to impact pressure. It preferably contains cetyl.
The tablet of the present invention does not contain the addition of a low melting point oily substance.
Addition of a low-melting oily substance improves the sliding of the drug particles and prevents damage to the drug crystals, but weakens the bond between the particles that make up the tablet (such as entanglement between the particles) and improves moldability. It deteriorates and requires a high tableting pressure in order to obtain a practical tablet hardness, which also causes generation of a pressure sensitive substance. In this way, it is difficult to adjust the amount of low melting point oily substance added and the tableting pressure, and when subjected to heat and strong shearing force due to high tableting pressure, the drug becomes amorphous and the drug becomes amorphous. This may reduce the stability of the product and generate related substances.
The low melting point oily substance referred to in the present invention is in the form of an oil and fat and usually has a melting point of about 20 to 90 ° C. Examples thereof include hydrocarbons, higher fatty acids, higher alcohols, fatty acid esters of polyhydric alcohols, higher alcohol ethers of polyhydric alcohols, and polymers or copolymers of alkylene oxides. These are substances that may be added for the purpose of improving the sliding of drug particles inside the powder and preventing crystal damage during tableting.
Examples of hydrocarbons include n-heptadecane, n-octadecane, n-nonadecane, n-eicosane, n-heneicosan, n-docosan, n-tricosane, n-tetracosane, n-pentacosane, n-triacontane, n-pentacontane. Examples thereof include n-alkanes having 17 to 50 carbon atoms such as triacontane, n-tetracontane and n-pentacontane, and mixtures thereof (such as petrolatum, paraffin wax and microcrystalline wax). Examples of higher fatty acids include capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, lignoceric acid, serotic acid, and mixtures thereof, and higher fatty acids collected from natural fats and oils. .
Examples of the higher alcohol include lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, aralkyl alcohol and mixtures thereof, and higher alcohol collected from natural oil. Examples of fatty acid esters of polyhydric alcohols include alcohols having two or more hydroxyl groups in the molecule (for example, alkylene glycols such as ethylene glycol and propylene glycol, polyalkylene glycols such as polyethylene glycol, polypropylene glycol, and copolymers thereof, sorbitol, Sugars such as sucrose and frynose, intramolecular dehydrated compounds of sorbitol such as 1,5-sorbitan, 1,4-sorbitol, 3,6-sorbitan, glycerin, diethanolamine, pentaerythritol, etc.) and fatty acids (for example, acetic acid, propion) Acid, butyric acid, pelargonic acid, capric acid, undecylic acid, lauric acid, tridecylic acid, myristic acid, pentadecylic acid, palmitic acid, heptadecylic acid, stearic acid, nonadecanoic acid, undecy Acid, oleic acid, elaidic acid, sorbic acid, linoleic acid, linolenic acid, arachidonic acid, stearolic acid, etc.), specifically sorbitan monostearate, sorbitan tristearate, sorbitan monooleate, Polyoxyls having a molecular weight of 1000 to 1500 such as sorbitan sesquioleate, sorbitan monopalmitate, etc., sorbitan fatty acid esters having a molecular weight of 400 to 900, polyoxyethylene sorbitan tristearate, polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan tripalmitate, etc. Alkylene sorbitan fatty acid ester, polyoxyethylene sorbitol hexastearate, polyoxyethylene sorbitol hexaoleate, polyoxyethylene sorbitol tris Polyoxyalkylene sorbitol fatty acid esters such as allate, polyoxyethylene sorbitol tetralaurate, polyoxyalkylene sorbitol dense wax derivatives such as polyoxyethylene sorbitol dense wax derivatives, polyoxyalkylene lanolin derivatives such as polyoxyethylene lanolin derivatives, propylene glycol Monopalmitate, propylene glycol monostearate, propylene glycol dilaurate, propylene glycol dimyristate, propylene glycol dipalmitate, propylene glycol distearate, etc., propylene glycol fatty acid ester having a molecular weight of 200 to 700, ethylene glycol monolaurate, ethylene glycol Palmitate, ethylene glycol margarate, ethylene glycol Cole stearate, ethylene glycol dilaurate, ethylene glycol dimyristate, ethylene glycol dipalmitate, ethylene glycol dimer gallate, etc., alkylene glycol fatty acid esters such as ethylene glycol fatty acid esters of molecular weight 500-1200, polyoxyethylene castor oil derivatives, etc., molecular weight 3500 -4000 polyoxyalkylene castor oil derivatives, polyoxyethylene stearate, polyoxyethylene oleate, polyoxyethylene palmitate, polyoxyethylene linoleate, etc., polyoxyalkylene fatty acid esters of molecular weight 1900-2200, glycerin monoacetate, glycerin Monopropionate, glycerin monostearate, glycerin monooleate, glycerin mono Glycerol monofatty acid ester with molecular weight of 300-600 such as luminate, glycerin monolinoleate, sucrose monolaurate, sucrose monomyristate, sucrose monopalmitate, sucrose monostearate, sucrose trimyristate, sucrose tripalmitate, sucrose tristearate And sucrose fatty acid esters having a molecular weight of 400 to 1300.
Examples of higher alcohol ethers of polyhydric alcohols include polyhydric alcohols (listed as alcohol components of fatty acid esters of the above polyhydric alcohols) and higher fatty acid alcohols (for example, cetyl alcohol, stearyl alcohol, oleyl alcohol, octyl alcohol, decyl alcohol). Ethers such as polyoxyethylene lauryl alcohol ether, polyoxyethylene cetyl alcohol ether, polyoxyethylene stearyl alcohol ether, polyoxyethylene oleyl alcohol ether, polyoxyethylene octyl alcohol ether, polyoxyethylene decyl alcohol ether Such as polyoxyethylene higher alcohol ether, polyoxypropylene polyoxyethylene cetyl alcohol ether Polyoxypropylene polyoxyethylene polyoxyethylene, such as tellurium, polyoxypropylene polyoxyethylene stearyl alcohol ether, polyoxypropylene polyoxyethylene oleyl alcohol ether, polyoxypropylene polyoxyethylene octyl alcohol ether, polyoxypropylene polyoxyethylene lauryl alcohol ether Examples include alcohol ethers.
As the polymer of alkylene oxide, one having a molecular weight of 1,000 to 10,000 (eg, polyethylene glycol 6000) is used. Examples of the alkylene oxide include ethylene oxide, propylene oxide, trimethylene oxide, tetrahydrofuran and the like (preferably ethylene oxide).
Examples of the alkylene oxide copolymer include copolymers of two or more of the above alkylene oxides and having a molecular weight of 1,000 to 10,000. These low melting point oils and fats are substances which are solid or liquid and may be added to the active ingredient.
Among these, polyethylene glycol, fatty acid ester, and higher alcohol may cause the amorphousness of drug crystals, and the addition is not preferable.
The tablet of the present invention needs to contain cellulose having an average L / D of 2.0 to 4.5.
The cellulose used in the present invention may be either crystalline cellulose or powdered cellulose, but crystalline cellulose is more preferable because of excellent moldability.
L / D is an optical microscopic image of the particles, using an air jet sieve (ALPINE, A200LS type), with the particles passed through a JIS standard sieve 75 μm in a pre-scattered state so that the individual particles do not get entangled. Image analysis processing (Image hyper, manufactured by Interquest Co., Ltd.) is obtained as the ratio of the long side to the short side (long side / short side) of the rectangle having the smallest area among the rectangles circumscribing the particles. The average L / D of the particles is determined by obtaining L / D of at least 400 particles.
When the average L / D is less than 2.0, the generation of related substances cannot be suppressed, and when the average L / D exceeds 4.5, the fiber property of cellulose is increased, and the moldability is decreased. Sufficient tablet hardness cannot be obtained. Also, if the pressing force is increased forcibly, the generation of related substances cannot be suppressed.
Preferably average L / D is 2.5-4.5, More preferably, it is 3.0-4.5.
Examples of crystalline cellulose having an average L / D of 2.5 to 4.5 include (trade name) Theolas KG-802 (Asahi Kasei Chemicals) and (trade name) Theolas KG-1000 (Asahi Kasei Chemicals).
The content of the pressure sensitive drug in the present invention is preferably 0.1 to 99% by weight, more preferably 0.1 to 95% by weight, and still more preferably 0.1 to 70% by weight. If it is 0.1% by weight or more, a sufficient healing effect can be easily obtained, and if it is 99% by weight or less, the amount of the excipient is sufficient and the hardness is likely to be practical.
In the present invention, the content of cellulose having an average L / D of 2.0 to 4.5 is preferably 1 to 99.9% by weight, more preferably 5 to 99.9% by weight, and further preferably 30 to 99.9%. % By weight. Since the effect of suppressing the generation of related substances of the pressure sensitive drug is great, the higher the cellulose content, the better.
In this invention, you may add pharmaceutical additives other than the above, such as a disintegrating agent and a lubricant, in the range which does not impair the effect of invention.
The hammering pressure sensitive agent and the components to be blended can be mixed in a mixer generally used in the manufacture of pharmaceuticals such as a tumbler mixer and a V-type mixer. Further, in the case of a laboratory level experiment, mixing using a plastic bag may be used.
The mixed powder is compression-molded with a tableting machine to form tablets. As the tableting machine, a rotary tableting machine generally used for tablet production and a single tableting machine used for laboratory-level experiments can be used. The tableting pressure at the time of tableting needs to be a condition for obtaining a tablet hardness that is a practical hardness. Tablets that do not have practical hardness are prone to wear and are not suitable for practical use.
Tablet production methods include direct compression, dry granulation, and wet granulation, but the wet granulation method decomposes the drug when used for moisture-unstable drugs. , Related substances may be generated. In the dry granule tableting method, after compressing the medicinal ingredients and excipients, the tablet is crushed and sized to give the desired particle size, so the drug crystals are subjected to strong force many times during the manufacturing process. Crystals are distorted and related substances are easily generated. These can be prevented by using a direct tableting method in which a powder mixture of a medicinal ingredient and various excipients is directly compression molded.
Practical hardness is tablet hardness of 30N or more for 4-6mm diameter; tablet hardness of 50N or more for diameter of 6-9mm; tablet hardness of 70N or more for diameter of 9-11mm; tablet hardness of 100N or more for diameter of 11-15mm, 150N or more for diameter of 15mm or more Refers to tablets. Tablets that meet practical hardness will not break during manufacturing or transportation.
According to the guidelines of the Ministry of Health, Labor and Welfare (Non-Patent Document 1), it is said that the amount of related substances generated is small, and if the amount of related substances exceeds 0.15%, the safety of related substances Since it is necessary to confirm the property, it is preferably 0.15% or less.
The tablet of this invention can reduce the generation amount of a related substance compared with the conventional tablet. In particular, in a tablet containing candesartan cilexetil, the amount of related substances generated after storage for 6 months in an environment of a temperature of 25 ° C. and a humidity of 58% RH can be suppressed to 0.15% or less.
The present invention will be specifically described based on examples.
The physical property measuring method and conditions used in the present invention are as follows.
<Measurement of related substances>
The tablets are dissolved in the mobile phase so that the drug concentration is 160 mg / L, filtered through a PTFE syringe filter with a pore of 0.45 μm to remove insoluble materials, and then HPLC (model LC-10ADVP, manufactured by Shimadzu Corporation) is used. taking measurement.
The tablets are dissolved in the mobile phase so that the drug concentration is 160 mg / L, filtered through a PTFE syringe filter with a pore of 0.45 μm to remove insoluble materials, and then HPLC (model LC-10ADVP, manufactured by Shimadzu Corporation) is used. taking measurement.
The analysis conditions are as follows.
Column: Phenomenex Luna C18 (2), Φ4.6 mm × 250 mm
Column temperature: 35 ° C
Mobile phase: acetonitrile: 0.1 M sodium dihydrogen phosphate aqueous solution: triethylamine = 65: 35: 0.1 [vol. %] Was adjusted to pH 3.9 by adding phosphoric acid to the mixed solution.
Flow rate: 1.0 mL / min
Injection volume: 5 μL / analysis Detection: UV detector (model SPD-10AVP, manufactured by Shimadzu Corporation), wavelength 262 nm
Column: Phenomenex Luna C18 (2), Φ4.6 mm × 250 mm
Column temperature: 35 ° C
Mobile phase: acetonitrile: 0.1 M sodium dihydrogen phosphate aqueous solution: triethylamine = 65: 35: 0.1 [vol. %] Was adjusted to pH 3.9 by adding phosphoric acid to the mixed solution.
Flow rate: 1.0 mL / min
Injection volume: 5 μL / analysis Detection: UV detector (model SPD-10AVP, manufactured by Shimadzu Corporation), wavelength 262 nm
From the chromatogram obtained under the above conditions, the areas of the drug main body peak (retention time 13.5 minutes) and the main related substance peak (retention time 6.5 minutes) were obtained, and (the peak area of the main related substance) ÷ Calculate the amount of related substances by (peak area of drug body).
<Amount of related substances generated>
Using the same measurement method as above, the amount of related substance (A) immediately after tableting and the amount of related substance (B) after storage for 6 months in a thermo-hygrostat set at a temperature of 25 ° C. and a humidity of 58% RH Measured and calculated from the following formula.
Amount of related substances generated = BA
Using the same measurement method as above, the amount of related substance (A) immediately after tableting and the amount of related substance (B) after storage for 6 months in a thermo-hygrostat set at a temperature of 25 ° C. and a humidity of 58% RH Measured and calculated from the following formula.
Amount of related substances generated = BA
<Measurement of tablet hardness>
Using a Schleingel hardness tester (model 8M, manufactured by PHAMATRON), the load necessary to break the tablet is obtained, and the average value of the three tablets is calculated. In the case of a non-circular tablet such as a caplet (elliptical shape), the linear distance of the longest part of the tablet is the tablet diameter.
Tablet diameter 4-6 mm: Tablet hardness 30 N or more Tablet diameter 6-9 mm: Tablet hardness 50 N or more Tablet diameter 9-11 mm: Tablet hardness 70 N or more Tablet diameter 11-15 mm: Tablet hardness 100 N or more Tablet diameter 15 mm or more: Tablet hardness 150N or more
Using a Schleingel hardness tester (model 8M, manufactured by PHAMATRON), the load necessary to break the tablet is obtained, and the average value of the three tablets is calculated. In the case of a non-circular tablet such as a caplet (elliptical shape), the linear distance of the longest part of the tablet is the tablet diameter.
Tablet diameter 4-6 mm: Tablet hardness 30 N or more Tablet diameter 6-9 mm: Tablet hardness 50 N or more Tablet diameter 9-11 mm: Tablet hardness 70 N or more Tablet diameter 11-15 mm: Tablet hardness 100 N or more Tablet diameter 15 mm or more: Tablet hardness 150N or more
[Test Example 1] (Confirmation that it is a pressure sensitive drug)
Put 5g of candesartan cilexetil powder and crystalline cellulose, 4g of Theolas PH-102 (Asahi Kasei Chemicals), lactose (SuperTAB 11SD, DMV-Fonterra Excipients) into a 1g plastic bag, mix for 3 minutes, and punch with a single tablet machine Tableting was performed at a pressure of 2 kN, 3 kN, 4 kN, and 5 kN to obtain a tablet having a diameter of 8 mm and a tablet weight of 200 mg. The obtained tablets are sealed with a glass bottle, stored for 3 months at an ambient atmosphere of 25 ° C. and a humidity of 58% RH, and the amount of related substances generated is as shown in Table 1. Was confirmed.
Put 5g of candesartan cilexetil powder and crystalline cellulose, 4g of Theolas PH-102 (Asahi Kasei Chemicals), lactose (SuperTAB 11SD, DMV-Fonterra Excipients) into a 1g plastic bag, mix for 3 minutes, and punch with a single tablet machine Tableting was performed at a pressure of 2 kN, 3 kN, 4 kN, and 5 kN to obtain a tablet having a diameter of 8 mm and a tablet weight of 200 mg. The obtained tablets are sealed with a glass bottle, stored for 3 months at an ambient atmosphere of 25 ° C. and a humidity of 58% RH, and the amount of related substances generated is as shown in Table 1. Was confirmed.
[Example 1]
A plastic bag containing 5 g of candesartan cilexetil powder, which is a pressure sensitive drug, 4 g of crystalline cellulose having an average L / D of 3.2 (Theolas KG-1000, Asahi Kasei Chemicals), and 1 g of lactose (SuperTAB 11SD, DMV-Fonterra Excipients) The mixture was mixed for 3 minutes, 200 mg was weighed, filled into a mortar, and tableted using a single tableting machine (model 1321DW, manufactured by Aiko Engineering) with a tableting pressure of 2.5 kN held for 10 seconds ( Direct compression), flat tablets with a diameter of 8 mm and 200 mg were obtained. The hardness of the obtained tablet was 55 N, and it was confirmed that the practical hardness was satisfied. Table 2 shows the physical properties of the obtained tablets.
A plastic bag containing 5 g of candesartan cilexetil powder, which is a pressure sensitive drug, 4 g of crystalline cellulose having an average L / D of 3.2 (Theolas KG-1000, Asahi Kasei Chemicals), and 1 g of lactose (SuperTAB 11SD, DMV-Fonterra Excipients) The mixture was mixed for 3 minutes, 200 mg was weighed, filled into a mortar, and tableted using a single tableting machine (model 1321DW, manufactured by Aiko Engineering) with a tableting pressure of 2.5 kN held for 10 seconds ( Direct compression), flat tablets with a diameter of 8 mm and 200 mg were obtained. The hardness of the obtained tablet was 55 N, and it was confirmed that the practical hardness was satisfied. Table 2 shows the physical properties of the obtained tablets.
[Example 2]
The crystalline cellulose in Example 1 was changed to crystalline cellulose having an average L / D of 2.8 (Theorus KG-802, Asahi Kasei Chemicals). A tablet having a practical hardness of 30 kN and a tablet hardness of 52 N was obtained. Table 2 shows the physical properties of the obtained tablets.
The crystalline cellulose in Example 1 was changed to crystalline cellulose having an average L / D of 2.8 (Theorus KG-802, Asahi Kasei Chemicals). A tablet having a practical hardness of 30 kN and a tablet hardness of 52 N was obtained. Table 2 shows the physical properties of the obtained tablets.
[Example 3]
The blending ratio of the pressure sensitive drug and crystalline cellulose in Example 1 was changed.
6 g of candesartan cilexetil powder, which is a pressure sensitive drug, and 4 g of crystalline cellulose having an average L / D of 3.2 (Theoras KG-1000, Asahi Kasei Chemicals) were mixed in the same manner as in Example 1 and then mixed with a single tableting machine. Tableting was performed (direct tableting method). A tablet satisfying the practical hardness with a punching pressure of 2.0 kN and a tablet hardness of 51 N was obtained. Table 2 shows the physical properties of the obtained tablets.
The blending ratio of the pressure sensitive drug and crystalline cellulose in Example 1 was changed.
6 g of candesartan cilexetil powder, which is a pressure sensitive drug, and 4 g of crystalline cellulose having an average L / D of 3.2 (Theoras KG-1000, Asahi Kasei Chemicals) were mixed in the same manner as in Example 1 and then mixed with a single tableting machine. Tableting was performed (direct tableting method). A tablet satisfying the practical hardness with a punching pressure of 2.0 kN and a tablet hardness of 51 N was obtained. Table 2 shows the physical properties of the obtained tablets.
[Example 4]
The crystalline cellulose in Example 3 was changed to crystalline cellulose having an average L / D of 2.8 (Theorus KG-802, Asahi Kasei Chemicals). A tablet satisfying the practical hardness, with a tableting pressure of 2.75 kN and a tablet hardness of 53 N, was obtained. Table 2 shows the physical properties of the obtained tablets.
The crystalline cellulose in Example 3 was changed to crystalline cellulose having an average L / D of 2.8 (Theorus KG-802, Asahi Kasei Chemicals). A tablet satisfying the practical hardness, with a tableting pressure of 2.75 kN and a tablet hardness of 53 N, was obtained. Table 2 shows the physical properties of the obtained tablets.
[Comparative Example 1]
The crystalline cellulose in Example 1 was changed to crystalline cellulose having an average L / D of 1.3 (Ceolus PH-102, Asahi Kasei Chemicals). A tablet satisfying the practical hardness with a punching pressure of 4.0 kN and a tablet hardness of 58 N was obtained. Table 2 shows the physical properties of the obtained tablets.
The crystalline cellulose in Example 1 was changed to crystalline cellulose having an average L / D of 1.3 (Ceolus PH-102, Asahi Kasei Chemicals). A tablet satisfying the practical hardness with a punching pressure of 4.0 kN and a tablet hardness of 58 N was obtained. Table 2 shows the physical properties of the obtained tablets.
[Comparative Example 2]
The crystalline cellulose in Example 1 was changed to a crystalline cellulose having an average L / D of 1.2 (Ceolus PH-200, Asahi Kasei Chemicals). A tablet satisfying the practical hardness with a punching pressure of 4.5 kN and a tablet hardness of 55 N was obtained. Table 2 shows the physical properties of the obtained tablets.
The crystalline cellulose in Example 1 was changed to a crystalline cellulose having an average L / D of 1.2 (Ceolus PH-200, Asahi Kasei Chemicals). A tablet satisfying the practical hardness with a punching pressure of 4.5 kN and a tablet hardness of 55 N was obtained. Table 2 shows the physical properties of the obtained tablets.
[Comparative Example 3]
The crystalline cellulose in Example 3 was changed to a crystalline cellulose having an average L / D of 1.3 (Ceolus PH-102, Asahi Kasei Chemicals). A tablet satisfying the practical hardness with a punching pressure of 4.0 kN and a tablet hardness of 54 N was obtained. Table 2 shows the physical properties of the obtained tablets.
The crystalline cellulose in Example 3 was changed to a crystalline cellulose having an average L / D of 1.3 (Ceolus PH-102, Asahi Kasei Chemicals). A tablet satisfying the practical hardness with a punching pressure of 4.0 kN and a tablet hardness of 54 N was obtained. Table 2 shows the physical properties of the obtained tablets.
[Comparative Example 4]
The crystalline cellulose in Example 3 was changed to a crystalline cellulose having an average L / D of 1.2 (Ceolus PH-200, Asahi Kasei Chemicals). A tablet satisfying the practical hardness with a punching pressure of 4.7 kN and a tablet hardness of 55 N was obtained. Table 2 shows the physical properties of the obtained tablets.
The crystalline cellulose in Example 3 was changed to a crystalline cellulose having an average L / D of 1.2 (Ceolus PH-200, Asahi Kasei Chemicals). A tablet satisfying the practical hardness with a punching pressure of 4.7 kN and a tablet hardness of 55 N was obtained. Table 2 shows the physical properties of the obtained tablets.
[Comparative Example 5]
In Example 1, the amount of lactose was changed from 1.0 g to 0.5 g, and the formulation was further changed to 0.5 g of polyethylene glycol 6000. A tablet satisfying the practical hardness with a punching pressure of 6 kN and a tablet hardness of 54 N was obtained. Table 2 shows the physical properties of the obtained tablets.
In Example 1, the amount of lactose was changed from 1.0 g to 0.5 g, and the formulation was further changed to 0.5 g of polyethylene glycol 6000. A tablet satisfying the practical hardness with a punching pressure of 6 kN and a tablet hardness of 54 N was obtained. Table 2 shows the physical properties of the obtained tablets.
[Comparative Example 6]
Candesartan cilexetil (1.0 g), D-mannitol (11.4 g) and corn starch (2.5 g) were placed in a mortar, and a solution of povidone (0.1 g) in pure water (1.9 g) was added and kneaded and granulated. The obtained granulated product was compression molded with a tableting pressure of 1.0 kN and a diameter of 8 mm and a weight of 225 mg, and then dried with a shelf dryer at 40 ° C. to obtain a tablet having a weight of 200 mg. The hardness of the obtained tablet was 65 N, and it was confirmed that the practical hardness was satisfied. Table 2 shows the physical properties of the obtained tablets.
Candesartan cilexetil (1.0 g), D-mannitol (11.4 g) and corn starch (2.5 g) were placed in a mortar, and a solution of povidone (0.1 g) in pure water (1.9 g) was added and kneaded and granulated. The obtained granulated product was compression molded with a tableting pressure of 1.0 kN and a diameter of 8 mm and a weight of 225 mg, and then dried with a shelf dryer at 40 ° C. to obtain a tablet having a weight of 200 mg. The hardness of the obtained tablet was 65 N, and it was confirmed that the practical hardness was satisfied. Table 2 shows the physical properties of the obtained tablets.
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The tablet of the present invention can be suitably used in the field of pharmaceutical preparations containing a drug having pressure sensitivity.
Claims (2)
- A tablet obtained by direct compression, containing a pressure sensitive drug and cellulose having an average L / D of 2.0 to 4.5 and no low melting point oily substance.
- The tablet according to claim 1, wherein the pressure sensitive drug is candesartan cilexetil.
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| JP2012095931AJP2013224265A (en) | 2012-04-19 | 2012-04-19 | Tablet containing strike-sensitive drug |
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| JP2012095931APendingJP2013224265A (en) | 2012-04-19 | 2012-04-19 | Tablet containing strike-sensitive drug |
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| WO2014088123A1 (en) * | 2012-12-05 | 2014-06-12 | Sawai Pharmaceutical Co., Ltd. | Candesartan cilexetil-containing preparation |
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