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
  • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
  • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
  • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
  • A61K31/445—Non condensed piperidines, e.g. piperocaine
  • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
  • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
  • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• • 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
  • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P19/00—Drugs for skeletal disorders
  • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P19/00—Drugs for skeletal disorders
  • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
  • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P9/00—Drugs for disorders of the cardiovascular system
  • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P9/00—Drugs for disorders of the cardiovascular system
  • A61P9/12—Antihypertensives

Definitions

• the present invention relates to a rapidly dissolving pharmaceutical composition containing venidipine hydrochloride and the like for promoting rapid absorption of the main drug, benidipine hydrochloride.
• Bendidipine hydrochloride a dihydropyridine calcium antagonist
• Benidipine hydrochloride is known to act on osteoblasts and osteoblasts, unlike other calcium antagonists such as difludipine and amlodipine, and to have an osteoprotective effect without impairing bone formation.
• lipophosphatase which is widely known as an indicator of osteoblast activity, is increased, acts on bone metabolism, and stimulates osteoblast function.
• Benidipine hydrochloride has a very low solubility in aqueous solvents, so it is not suitable for oral administration. It is necessary to devise such a method that the drug is rapidly eluted from the pharmaceutical composition in the gastrointestinal fluid. Disclosure of the invention
• An object of the present invention is to provide a rapidly dissolving benidipine hydrochloride-containing pharmaceutical composition and the like for promoting rapid recovery of the main drug, benidipine hydrochloride.
• the present invention relates to the following (1) to (20).
• Vedidipine hydrochloride crystals having a volume average particle diameter of 1.0 to 50.0 m, or volume average particle diameters containing benzyldipine hydrochloride crystals and functional additives having water solubility or water affinity of 1,0 to 50.0 m
• Benidipine hydrochloride crystals having a volume average particle diameter and a number average particle diameter of 4.5 to 30.0 ⁇ m, or a volume average particle diameter containing a benidivine hydrochloride crystal and a water-soluble or water-affinity functional additive 4.5
• the weight ratio of the penididipine hydrochloride crystals to the water-soluble or water-affinity functional additive is The pharmaceutical composition according to the above (1) or (2), wherein the ratio is 1:99 to 99: 1.
• the water-soluble or water-affinity functional additive has a water-solubility or water-affinity additive.
• the pharmaceutical composition according to any one of the above-mentioned) to (3), which is a form.
• water-soluble or water-affinity excipients may contain starches, starch derivatives, sugars, and sugars.
• the water-soluble or water-affinity functional additive is a disintegrant.
• the pharmaceutical composition according to any of (3).
• the water-soluble or water-affinity functional additive is water-soluble or water-soluble.
• the volume average particle size of the penidipine hydrochloride crystals is 1.0 to 50.0 m, or a functional additive having water-soluble or water-affinity crystals of benidipine hydrochloride.
• the volume average particle diameter of the granules containing benidipine hydrochloride crystals and a functional additive having water solubility or water affinity is 1.0 to 50.0 ⁇ m.
• the volume average particle size and number average size of the benidipine hydrochloride crystals should be 4.5 to 30.0 ⁇ m, or the benidipine hydrochloride crystals and water-soluble or water-soluble
• the volume average particle diameter of the granule containing the benidipine hydrochloride crystal and the water-soluble or water-affinity functional additive is determined.
• the water-soluble or water-affinity functional additives have water-solubility or water-affinity
• excipients having water solubility or water affinity may contain starches, starch derivatives, sugars, sugars, etc.
• Benidipine hydrochloride crystals and water-soluble or water-affinity functional additives The quick dissolution method according to any one of the above (11) to (15), wherein the functional additive having water solubility or water affinity in the contained powdery granules is a disintegrant.
• the water-soluble or water-affinity functional additives have water-solubility or water-affinity
• the pharmaceutical composition of the present invention preferably contains benidipine hydrochloride and exhibits a D30min value of about 40% to 100% (dissolution rate of benidipine hydrochloride at 30 minutes in a dissolution test).
• the conditions for the dissolution test at this time are the same as the conditions for the dissolution test described in the test examples described below.
• Water affinity refers to the property of attracting water molecules by some kind of interaction such as electrostatic interaction or hydrogen bonding.
• the volume average particle diameter of the benidipine hydrochloride crystals in the present invention is L0-50.0-111, preferably 4.5-50.0 / m, more preferably 4.5-30.0111.
• the powder of the present invention containing penidipine hydrochloride and a water-soluble or water-affinity functional additive has an adiabatic particle size of 1.0 to 50.0 in and 4.5 to 50.0 m. And more preferably 4.5 to 30.0 m.
• the weight ratio with the functional additive having compatibility is preferably from 1:99 to 99: 1, more preferably from 1:50 to 1: 2, and even more preferably from 1:40 to 1: 1. : 4
• the granular material containing the functional additive having the property is preferably a number average particle diameter of 1.0 to 50.0 ⁇ m, more preferably 4.5 to 30.0 // m, and a volume average particle diameter. More preferably, the difference in the number average particle diameter is 50% or less of the volume average particle diameter. Alternatively, the volume average particle diameter is preferably 12 to 50.0 m, regardless of the number average particle diameter. With these preferred average particle sizes, the quality of the pharmaceutical composition such as the stability of benidipine hydrochloride and the uniformity of the content of penidipine hydrochloride can be better maintained.
• water-soluble or water-affinity functional additives examples include water-soluble or water-affinity excipients, disintegrants, and water-soluble or water-affinity binders.
• water-soluble or water-compatible excipients include starches such as wheat starch, rice starch, corn starch, potato starch, modified starch, partially arsenic starch, starch derivatives such as hydroxypropyl starch, and lactose.
• Sugars such as glucose, maltose and pullulan, sugar alcohols such as D-mannitol, sorbitol, erythritol, xylitol, lactitol, maltitol, celluloses such as crystalline cellulose, carmellose, carmellose sodium, croscar Cellulose such as sodium melose, methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, dexamethasylmethylcellulose Scan derivatives, dextrin and the like,
• the amount of the excipient having a water-soluble or water affinity, a pharmaceutical composition from 40 to 95 mass% is preferred, more preferably 60 to 95 wt%.
• Disintegrators include, for example, starches such as wheat starch, rice starch, corn starch, potato starch, starch derivatives such as oxystarch, partially arsenic starch, hydroxypropyl starch, celluloses such as crystalline cellulose, carmellose, carme Cellulose derivatives such as sodium cellulose, croscarmellose sodium, methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose and carboxyethylmethylcellulose.
• the amount of the disintegrant having the property is 1 to 10 mass in the pharmaceutical composition. /. And more preferably 2 to 5% by mass.
• water-soluble or water-affinity binder examples include cellulosic substances such as crystalline cellulose, carmellose, carmellose sodium, croscarmellose sodium, and the like.
• Cellulose derivatives such as methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, carboxyethylmethylcellulose, polyvinyl alcohol, partially saponified polyvinyl alcohol, polyvinylpyrrolidone, etc.
• the amount of the binder having water affinity to be used is preferably 0.1 to 10% by mass, more preferably 0.5 to 5% by mass in the pharmaceutical composition. /. It is.
• the functional additive having water solubility or water affinity is contained in a pharmaceutical composition other than the granular material.
• the amount of the water-soluble or water-affinity functional additive contained in the pharmaceutical composition other than the powdery granules is, for example, water-soluble or water-affinity excipients.
• the total amount of the pharmaceutical composition in the granules and the pharmaceutical composition other than the granules is preferably 40 to 95% by mass, more preferably 60 to 95% by mass. It is preferable that the total amount of the pharmaceutical composition in the above-mentioned granular material and the pharmaceutical composition other than the above-mentioned granular material is 1 to 30% by mass, more preferably 2 to 15% by mass.
• the excipient having water affinity it is preferable that the total amount of the pharmaceutical composition in the granular material and the pharmaceutical composition other than the granular material is 0.1 to 30% by mass. Preferably it is 0.5 to 15% by mass.
• the pharmaceutical composition of the present invention contains, in addition to the above-mentioned water-soluble or water-affinity functional additives, other pharmaceutical additives generally used in the field of pharmaceuticals, such as lubricants, foaming agents, and sweeteners. Agents, fragrances, coloring agents and the like can also be added.
• Lubricants include, for example, stearic acid, calcium stearate, magnesium stearate, polyoxyl 40 stearate, talc, ceanol, lab wax, caffeic anhydride, paraffin, boric acid, leucine, polyoxyethylene fatty acid ester, benzoic acid Acid sodium and the like.
• the amount of the lubricant used is 0.01 to 1 mass in the pharmaceutical composition. /. And more preferably 0.01 to 0.5% by mass.
• foaming agent examples include sodium hydrogen carbonate, sodium carbonate, calcium carbonate and the like.
• sweetener examples include aspartame (registered trademark), saccharin, glycyrrhizin and the like.
• flavors include lemon, orange, pine, mint, and menthol. It is.
• coloring agent examples include yellow iron dioxide, iron sesquioxide, and evening pigment.
• coating examples include sugar coating, film coating, polymer coating, and the like. The purpose of coating is, for example, by imparting flavor, gastric or enteric solubility, and oxidation or hydrolysis of a drug. Prevention of deterioration.
• Coating agents used for coating for flavoring include, for example, methylcellulose, ethylcellulose, hydroxyethylmethylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, methyl methacrylate Butyl acrylate / dimethylaminoethyl methacrylate 'copolymer (E;), ethyl acrylate / methyl methacrylate / methyl methacrylate methacrylate-copolymer (RS) and the like.
• Examples of the coating agent used for coating for imparting gastric solubility include methyl methacrylate 'butyl methacrylate' dimethylaminoethyl methacrylate copolymer (E), polyvinyl acetate yurujethylamino acetate (AEA) And so on.
• Examples of coating agents used for coating for imparting enteric properties include methacrylic acid / methyl methacrylate / copolymer (L), methacrylic acid / ethyl acrylate / copolymer (LD), and acetic acid.
• L methacrylic acid / methyl methacrylate / copolymer
• LD methacrylic acid / ethyl acrylate / copolymer
• acetic acid Cellulose, cellulose acetate fluorate, carboxymethyl cellulose, hydroxypropylmethylcellulose acetate succinate, hydroxyoxypropylmethyl cellulose monophthalate and the like can be mentioned.
• the pulverizer used for pulverizing the benidipine hydrochloride crystals is not particularly limited, but a hammer mill, a jet mill or the like is preferably used.
• Benidipi hydrochloride Can be processed to have a volume average particle size of 1.0 to 50.0 ⁇ m, preferably 4.5 to 50 ⁇ 0 ⁇ , more preferably 4.5 to 30.0 zm.
• the number average particle diameter is preferably 1.0 to 50.0 zm, more preferably 4.5 to 30.0 ⁇ m, and further preferably the difference between the volume average particle diameter and the number average particle diameter is the volume average particle diameter. To 50% or less. Alternatively, it can be processed so that the volume average particle diameter is 12 to 50.0 zm, regardless of the number average particle diameter.
• benidipine hydrochloride can be processed to have a volume average particle size of 1.0 to 5.0.0 mm by sieving, crystallization, spray drying, or the like.
• the powder containing the benidipine hydrochloride crystal and the water-soluble or water-affinity functional additive is pulverized after adding the water-soluble or water-affinity functional additive to the benidipine hydrochloride crystal. It can be processed to have a volume average particle size of 1.0 to 50.0 ⁇ m, preferably 4.5 to 50.0 im, and more preferably 4.5 to 30.0 ⁇ m by sieving, crystallization, drying and the like.
• the number average particle diameter; L 0 to 50.0, more preferably 4.5 to 30.0 im, still more preferably the volume average particle diameter and the number average Processing can be performed so that the difference in particle size is 50% or less of the volume average particle size.
• processing can be performed so that the volume average particle diameter is 12 to 50.0 zm, regardless of the number average particle diameter.
• benidipine hydrochloride crystals processed to have a volume average particle size of 1.0 to 50.0 m or powdered granules containing benidipine hydrochloride and a water-soluble or water-affinity functional additive may be added, if necessary.
• Granulation is performed by adding the above-mentioned various pharmaceutical additives to obtain a granulated product.
• the method of granulation is not particularly limited, but wet granulation is preferably used.
• the granulator for example, a fluidized bed granulator, a tumbling stirring granulator, an extrusion granulator and the like are used.
• vendidipine hydrochloride used in the pharmaceutical composition containing vendidipine hydrochloride of the present invention varies depending on the dose and the like, but is preferably 0.01 to 50% by mass, more preferably 0.01 to 30% by mass in the tablet.
• the tableting machine used for the compression molding is not particularly limited, but it is preferable to use a mouthless tableting machine, and the compression molding pressure is preferably from 300 kg to 5000 kg.
• the pharmaceutical composition may be coated for imparting flavor, gastric solubility or enteric solubility, etc., but this is done by coating the granulated product, that is, the raw granules before compression molding. And a method of coating tablets after compression molding.
• the active ingredient benidipine hydrochloride crystals are attached together with a binder to lactose or the spherical granules of the crystal cell mouth and allowed to stand.
• the granules are dried by a tray dryer, a fluidized bed dryer or the like to obtain elementary granules containing benidipine hydrochloride crystals.
• the coating agent is mixed with a suitable solvent, for example, water, methanol, ethanol, 2-propanol, ethyl acetate, ethyl lactate, acetone, methylene chloride, 1,1,1-trichloromethane.
• a suitable solvent for example, water, methanol, ethanol, 2-propanol, ethyl acetate, ethyl lactate, acetone, methylene chloride, 1,1,1-trichloromethane.
• the coated powder is sprayed onto the elementary granules and coated with the coating agent solution dissolved or dispersed in ethane or the like or a mixed solvent of these, and dried with a standing-bed dryer or fluidized-bed dryer. Obtain granules.
• the coating apparatus at this time is not particularly limited, but preferably a fluidized bed coating drying apparatus, a centrifugal fluidized granulation apparatus, a tumbling fluidized coating drying apparatus and the like are used.
• the coating apparatus used for coating the tablets after compression molding is not particularly limited, but a drum-type film coating drying apparatus or a fluidized-bed coating apparatus is preferably used.
• Immediate elution of venidipine hydrochloride from the pharmaceutical composition of the present invention can be achieved by adjusting the volume average particle diameter of the penidipine hydrochloride crystals to 1.0 50.0 m, preferably, in a pharmaceutical composition containing venidipine hydrochloride.
• a pharmaceutical composition having an average particle size and a number average particle size of 4.5 to 30.0 m, or containing a benidipine hydrochloride crystal and a powder containing a water-soluble or water-affinity functional additive benidipine hydrochloride may be used.
• the volume average particle diameter of the powder containing the crystals and the functional additive having water-solubility or water-miscibility is adjusted to 1.0 to 50.0 ⁇ m, preferably 4.5 to 50,0 zm.
• a pharmaceutical composition containing benidipine hydrochloride by the above-mentioned method for producing a pharmaceutical composition of the present invention. Can be done.
• Benidipine hydrochloride drug substance (lot P-010, manufactured by Kyowa Hakko, volume average particle diameter 65.0 ⁇ m, number average particle diameter 10.3 ⁇ m) 5000g was fed to a grinder sample mill (KIIWG-IF type, manufactured by Fuji Padal) This was subjected to a single milling treatment. Further, the obtained pulverized penidipine hydrochloride crystals were subjected to a single pulverization treatment by a jet mill pulverizer (PJM-100SP, manufactured by Nippon Pneumatic Industries, Ltd.) to obtain pulverized benidipine hydrochloride crystals.
• PAM-100SP jet mill pulverizer
• the average particle size of the pulverized benidipine hydrochloride crystals was measured by an image analyzer under a microscope (Olympus SP-500) by a wet method using a liquid noraffin suspension.
• the pulverized penidipine hydrochloride crystals had a volume average particle diameter of 9.4111 and a number average particle diameter of 4.91.
• the pulverized benzodipine hydrochloride crystals, lactose and potato starch are granulated by a fluidized bed granulator under spraying of an aqueous solution of polyvinyl alcohol, and magnesium stearate is added as a lubricant to a V-type mixer.
• tablets were obtained by the following formulation and production method.
• crushed benzodivine hydrochloride crystals, lactose and potato starch are granulated with a fluidized bed granulator while spraying an aqueous solution of polyvinyl alcohol, and magnesium stearate is mixed in a V-shape as a lubricant.
• the mixture was mixed with a press to obtain granules for tableting.
• a tablet having a tablet diameter of 7 mg and a tablet weight of 130 mg was obtained.
• Benidipine hydrochloride drug substance (lot P-010, manufactured by Kyowa Hakko, volume average particle size 65,0 ⁇ 111, number average particle size 10.3 ⁇ m) was passed through a vibrating screen machine [100mesh (150 ⁇ m) sieve].
• a vibrating screen machine [100mesh (150 ⁇ m) sieve].
• the average particle size of the sieved benidipine hydrochloride crystals can be determined by a wet method using a fluid paraffin suspension under a microscope using an image analyzer (Olympus). SP-500).
• the sieved benidipine hydrochloride crystals had a volume average average particle diameter of 26.3 m and a number average particle diameter of 6.6 / m.
• the sieved venidipine hydrochloride crystals, lactose and potato starch are granulated in a fluidized bed granulator while spraying an aqueous solution of polyvinyl alcohol, and magnesium stearate is added as a lubricant to a V-type mixer.
• Tablets were obtained using the drug substance of Benidipine hydrochloride (Lot P-010, manufactured by Kyowa Hakko, volume average particle diameter 65.0 m, number average particle diameter 10.3 ⁇ m) according to the following formulation and production method.
• Benidipine hydrochloride drug substance (Lot P-010, manufactured by Kyowa Hakko, volume average particle diameter 65.0 Zffl, number average particle diameter 10.3 ⁇ ), lactose and potato starch are sprayed with an aqueous solution of polyvinyl alcohol, and the fluidized bed The mixture was granulated with a granulator, and magnesium stearate as a lubricant was further mixed with a V-type mixer to obtain granules for tableting. Using these granules for tableting, tablets having a tablet size of 7IM0 and a tablet weight of 130 mg were obtained.
• Tablets were obtained using the drug substance of Benidipine hydrochloride (Lot P-005, manufactured by Kyowa Hakko, volume average particle size 147.1 zm, number average particle size 9.7 ⁇ ffl) according to the following formulation and manufacturing method.
• Benidipine hydrochloride Lit P-005, manufactured by Kyowa Hakko, volume average particle size 147.1 zm, number average particle size 9.7 ⁇ ffl
• Benidipine hydrochloride drug substance (Lot P-005, manufactured by Kyowa Hakko, volume average particle diameter 147.1 m, number average particle diameter 9.7 ⁇ m), lactose and potato starch are sprayed with an aqueous solution of polyvinyl alcohol into a fluidized bed granulator. Then, magnesium stearate as a lubricant was mixed with a V-type mixer to obtain granules for tableting. Using these granules for tableting, tablets having a tablet size of 7 nm0 and a tablet weight of 130 mg were obtained.
• Table 1 shows the volume average particle size and the number average particle size of the benidipine hydrochloride crystals used in Examples 1, 2, and 3 and Comparative Examples 1 and 2.
• Example 1 9.4 / in 4.9 jLLOi
• Example 2 14.bj ⁇ 6.2 m
• Example 3 26.3 m 6,6 im Comparative example 1 65.0 rn 10.3 m
• Comparative Example 147.1 zm 9.7 ZJii Test Example: Dissolution Test
• the dissolution test was performed according to the Japanese Pharmacopoeia Method 1 (rotating basket method) using 900 ml of the test solution [sodium lauryl sulfate PH6.8 sodium phosphate buffer solution (1500)] at 37 ° C. Performed at 50 rpm.
• the eluate sampled 10, 20, 30, 45, and 60 minutes after the start of the test was subjected to high performance liquid chromatography [column: YMC A-301-1 (4.6 x 100 thighs), temperature; 40 ° moving bed: 0.05 mol / L aqueous solution of potassium dihydrogen phosphate / acetonitrile (55:45) + 1 aqueous ol / L aqueous solution of sodium lauryl sulfate], and evaluated as an elution profile.
• Table 2 shows the dissolution test results of the tablets obtained in Examples 1, 2, and 3 and Comparative Examples 1 and 2. Table 2 Dissolution test results.
• a medicinal composition containing benidipine hydrochloride and the like having a rapid dissolution property for promoting rapid absorption of the main drug, benidipine hydrochloride.

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• 2004
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