CN102266337A - Benidipine hydrochloride solid preparation and preparation method thereof - Google Patents
Benidipine hydrochloride solid preparation and preparation method thereof Download PDFInfo
- Publication number
- CN102266337A CN102266337A CN2010101972572A CN201010197257A CN102266337A CN 102266337 A CN102266337 A CN 102266337A CN 2010101972572 A CN2010101972572 A CN 2010101972572A CN 201010197257 A CN201010197257 A CN 201010197257A CN 102266337 A CN102266337 A CN 102266337A
- Authority
- CN
- China
- Prior art keywords
- preparation
- solid
- solid dispersion
- benidipine hydrochloride
- gram
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention provides a benidipine hydrochloride solid preparation and a preparation method thereof. The benidipine hydrochloride solid preparation comprises benidipine hydrochloride, solid dispersion carriers and functional auxiliary materials. In the benidipine hydrochloride solid preparation, highly decentralized benidipine hydrochloride has the characteristics of rapid dissolution and absorption. The preparation method of the benidipine hydrochloride solid preparation comprises the following steps of 1, dissolving benidipine hydrochloride in an appropriate organic solvent and adding the benidipine hydrochloride solution into molten solid dispersion carriers, or directly adding benidipine hydrochloride into the molten solid dispersion carriers and stirring the mixture until benidipine hydrochloride is dissolved, maintaining a molten state and stirring until the organic solvent is volatilized completely, cooling fast and crushing, or dissolving benidipine hydrochloride and solid dispersion carriers in an organic solvent, volatilizing the organic solvent completely and crushing, and 2, preparing the benidipine hydrochloride dispersion powder and functional auxiliary materials into particles through a certain granulation method, packaging directly the particles to obtain particulate agents, and filling the particulate agent into capsule bodies to obtain capsules or pressing the particulate agents into tablets.
Description
Technical field
The present invention relates to medical technical field, is a kind of KW-3049 solid preparation and preparation method thereof, and the dispersive KW-3049 of said preparation camber is understood rapid stripping, is inhaled in the body fast.
Background technology
KW-3049 is a dihydropyridine class calcium ion antagonist, and it combines by the dihydropyridine receptor with blocking-up cell membrane potential dependent form calcium channel, stops calcium ion to flow in the cell and distends the blood vessels.KW-3049 is as the medicine of the substantive hypertension of hypertension, kidney, angina pectoris etc., because safety, effectively be widely used.
In the process of treatment essential hypertension, calcium antagonist plays important effect as a class core drug, especially for old essential hypertension people.Studies show that; osteoporosis is a big common sympton that is accompanied by old essential hypertension people, and known benidipine can improve senile osteoporosis, bone density improving and intensity; strengthen to generally believe it is the alkaline phosphatase activity of making the bone active index, have the bone protective effect.Many studies show that, the bone protective effect of KW-3049 mainly is to realize by influencing the relevant Calcium Metabolism Regulation hormones such as parathyroid hormone of bone metabolism.
(parathyroid hormone is to keep the equilibrated a kind of important accent calcium hormone of body alcium and phosphor metabolization PTH) to parathyroid hormone, is important bone formation-promoter.The low concentration of parathyroid hormone or intermittent concentration raise and can promote the skeleton anabolism in the known blood, and the long-time rising of concentration of still working as parathyroid hormone in the blood can suppress the anabolism of skeleton on the contrary.The quick stripping of KW-3049 and rapid metabolism meeting cause the moment property rising of parathyroid hormone in the blood, and this moment property rising helps lend some impetus to the formation of bone.If the slow stripping of KW-3049 can cause the long-time rising of blood drug level in the body, the concentration of parathyroid hormone also can raise for a long time in the blood, thereby can suppress the synthetic of skeleton.
Therefore, be necessary to develop a kind of KW-3049 preparation, medicine stripping and metabolism rapidly fast also can promote the synthetic of bone in the hypertensive while of treatment after the administration, reduces the risk of osteoporosis.
Summary of the invention
The invention provides a kind of KW-3049 solid preparation, the stripping fast after administration of the dispersive KW-3049 of preparation camber enters in the body rapidly.
KW-3049 solid preparation of the present invention is made up of KW-3049, solid dispersion carrier and functional adjuvant, and its component and proportioning are as follows:
Constituent content (gram/gram)
KW-3049 0.01-30%, preferred 0.1-10%;
Solid dispersion carrier 0.01-60%, preferred 1-50%;
Functional adjuvant surplus.
Wherein,
The solid dispersion carrier is selected from one or more in Macrogol 4000, polyethylene glycol 6000, polyvinylpyrrolidone, pluronic F68, carbamide, citric acid, mannitol, xylitol, sorbitol and the erythritol, one or more in preferred Macrogol 4000, polyethylene glycol 6000 and the polyvinylpyrrolidone.
Functional adjuvant comprises hydrophilic filler, wetting agent, disintegrating agent, binding agent and fluidizer.
Hydrophilic filler in the functional adjuvant includes but not limited to starch based, starch derivatives, dextrin, inorganic salts, saccharide, sugar alcohols, cellulose family and cellulose derivative.Be exemplified below: starch based such as corn starch, wheaten starch, potato starch, potato starch, starch derivatives such as pregelatinized Starch, hydroxypropyl starch, dextrin, inorganic salts such as calcium sulfate, calcium hydrogen phosphate, calcium carbonate, lactose, glucose, maltose, sugar alcohols such as mannitol, xylitol, sorbitol, lactose, erythritol, cellulose families such as microcrystalline Cellulose, cellulose derivatives such as methylcellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose; Consumption is 1-95%, preferred 30-85%.
Wetting agent in the functional adjuvant is selected from one or more in sodium lauryl sulphate, polyoxyethylene castor oil, tween 20, Tween-60, tween 80, poloxamer 188, soybean lecithin, Ovum Gallus domesticus Flavus lecithin and the Brij-35; Consumption is 0-20%, preferred 0.1-5%.
Disintegrating agent in the functional adjuvant includes but not limited to cellulose family, cellulose derivative, starch based, starch derivatives, polyvinylpolypyrrolidone and gas-producing disintegrant.Be exemplified below: cellulose families such as crystalline cellulose, cellulose derivatives such as cross-linking sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, starch based such as corn starch, starch derivatives such as carboxymethyl starch sodium, hydroxypropyl starch, polyvinylpolypyrrolidone, gas-producing disintegrants such as sodium bicarbonate and citric acid; Consumption is 0-30%, preferred 1-10%.
Binding agent in the functional adjuvant includes but not limited to cellulose family, cellulose derivative and polyvidone.Be exemplified below: cellulose families such as microcrystalline Cellulose, cellulose derivatives such as methylcellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, 30 POVIDONE K 30 BP/USP 25,30 POVIDONE K 30 BP/USP 30,30 POVIDONE K 30 BP/USP 90; Consumption is 0.1-15%, preferred 0.5-5%.
Fluidizer in the functional adjuvant is selected from one or more in magnesium stearate, micropowder silica gel and the Pulvis Talci; Consumption is 0-3%, is preferably 0.1-1%.
KW-3049 solid preparation of the present invention, its preparation method is as follows:
(1) KW-3049 is added in the fused solid dispersion carrier after by suitable organic solvent dissolution, stir until organic solvent and wave to the greatest extent, pulverize the cooling back fast; Or directly KW-3049 is added in the fused solid dispersion carrier and to stir until medicine dissolution, cooling is fast pulverized then; Or KW-3049 and solid dispersion carrier be dissolved in the suitable organic solvent, wave most organic solvent then, pulverize;
(2) said medicine dispersion powder and functional adjuvant are prepared into granule by certain prilling process, gained granule directly packing is granule, and fill is capsule in capsule, also the gained granule can be pressed into tablet.
Used organic solvent is selected from one or more in ethanol, acetone, chloroform or the tert-butyl alcohol in the preparation process; Used prilling process does not limit its kind, preferred wet granulation method.
The specific embodiment
Below in conjunction with embodiment the present invention is described in detail.
Embodiment 1
1. the preparation of KW-3049 solid dispersion
Take by weighing 30 gram Macrogol 4000s in beaker, the heating in water bath fusion; 6 gram KW-3049 add in the fused Macrogol 4000 after with the anhydrous alcohol solution of 30ml heat, and stirring and evenly mixing continues to stir until dehydrated alcohol and waves to the greatest extent, and cooling is fast pulverized, and promptly gets the solid dispersion powder of medicine.
2. the capsular preparation of KW-3049 dispersion
Use above KW-3049 dispersion powder, obtain capsule according to following prescription and preparation method.
With KW-3049 dispersion powder, mannitol, lactose, sodium lauryl sulphate, carboxymethyl starch sodium mix homogeneously, under the sprinkling of 30 POVIDONE K 30 BP/USP 30 alcoholic solution, mixture is carried out pelletize, treat to add the magnesium stearate mixing again after the granule oven dry, fill is in capsule.Every piece of capsule contains granule 140mg.
Embodiment 2
1. the preparation of KW-3049 solid dispersion
Take by weighing 100 gram polyethylene glycol 6000s in beaker, the heating in water bath fusion; 4 gram KW-3049 are added in the fused polyethylene glycol 6000, stir until medicine dissolution, cooling is fast pulverized, and promptly gets the solid dispersion powder of medicine.
2. the capsular preparation of KW-3049 dispersion
Use above KW-3049 dispersion powder, obtain capsule according to following prescription and preparation method.
With KW-3049 dispersion powder, mannitol, microcrystalline Cellulose, sodium lauryl sulphate, carboxymethyl starch sodium mix homogeneously, under the sprinkling of 30 POVIDONE K 30 BP/USP 30 alcoholic solution, mixture is carried out pelletize, treat to add the magnesium stearate mixing again after the granule oven dry, fill is in capsule.Every piece of capsule contains granule 140mg.
Embodiment 3
1. the preparation of KW-3049 solid dispersion
Take by weighing 80 gram polyvinylpyrrolidone K30 and 20 gram KW-3049 in beaker, add the 400ml dehydrated alcohol it is dissolved, keep temperature, stirring and evenly mixing continues to stir until ethanol and waves to the greatest extent, and cooling is fast pulverized, and promptly gets the solid dispersion powder of medicine.
2. the capsular preparation of KW-3049 dispersion
Use above KW-3049 dispersion powder, obtain capsule according to following prescription and preparation method.
With KW-3049 dispersion powder, lactose, corn starch, poloxamer 188, carboxymethyl starch sodium mix homogeneously, under the sprinkling of 30 POVIDONE K 30 BP/USP 30 alcoholic solution, mixture is carried out pelletize, treat to add the magnesium stearate mixing again after the granule oven dry, fill is in capsule.Every piece of capsule contains granule 140mg.
Embodiment 4
1. the preparation of KW-3049 solid dispersion
Take by weighing 10 gram sorbitol, 20 gram xylitol in beaker, the heating in water bath fusion; 5 gram KW-3049 add in the above-mentioned fused mass after using the 20ml acetone solution, and stirring and evenly mixing continues to stir until acetone and waves to the greatest extent, and quick cooling is pulverized, and promptly gets the solid dispersion powder of medicine.
2. the capsular preparation of KW-3049 dispersion
Use above KW-3049 dispersion powder, obtain capsule according to following prescription and preparation method.
With KW-3049 dispersion powder, lactose, hydroxypropyl methylcellulose, poloxamer 188, carboxymethyl starch sodium mix homogeneously, under the sprinkling of 30 POVIDONE K 30 BP/USP 30 alcoholic solution, mixture is carried out pelletize, treat to add the magnesium stearate mixing again after the granule oven dry, fill is in capsule.Every piece of capsule contains granule 140mg.
Embodiment 5
1. the preparation of KW-3049 solid dispersion
Take by weighing 32 gram Macrogol 4000s and 8 gram xylitol in beaker, the heating in water bath fusion; 5.5 the gram KW-3049 adds in the fused Macrogol 4000 after with the anhydrous alcohol solution of 25ml heat, stirring and evenly mixing continues to stir until dehydrated alcohol and waves to the greatest extent, and cooling is fast pulverized, and promptly gets the solid dispersion powder of medicine.
2. the capsular preparation of KW-3049 dispersion
Use above KW-3049 dispersion powder, obtain capsule according to following prescription and preparation method.
With KW-3049 dispersion powder, lactose, corn starch, sodium lauryl sulphate, cross-linking sodium carboxymethyl cellulose mix homogeneously, under the sprinkling of 30 POVIDONE K 30 BP/USP 30 alcoholic solution, mixture is carried out pelletize, treat to add the magnesium stearate mixing again after the granule oven dry, fill is in capsule.Every piece of capsule contains granule 140mg.
Embodiment 6
1. the preparation of KW-3049 solid dispersion
Take by weighing 4 gram polyvinylpyrrolidones, 1 gram polyethylene glycol 6000 and 5 gram KW-3049 in beaker, add the 30ml dehydrated alcohol above-mentioned substance is dissolved, heating in water bath limit, limit is stirred until dehydrated alcohol and is waved to the greatest extent, fast cooling, pulverize, promptly get the solid dispersion powder of medicine.
2. the preparation of the tablet of KW-3049 dispersion
Use above KW-3049 dispersion powder, obtain tablet according to following prescription and preparation method.
With KW-3049 dispersion powder, dextrin, microcrystalline Cellulose, soybean phospholipid, poloxamer 188 mix homogeneously, under the sprinkling of 30 POVIDONE K 30 BP/USP 30 alcoholic solution, mixture is carried out pelletize, treat to add the micropowder silica gel mixing again after the granule oven dry, tabletting in single punch tablet machine, hardness 50N, the heavy 140mg of sheet.
Embodiment 7
1. the preparation of KW-3049 solid dispersion
Take by weighing 60 gram Macrogol 4000s in beaker, the heating in water bath fusion; 6 gram KW-3049 add in the fused Macrogol 4000 after with the anhydrous alcohol solution of 30ml heat, and stirring and evenly mixing continues to stir until dehydrated alcohol and waves to the greatest extent, and cooling is fast pulverized, and promptly gets the solid dispersion powder of medicine.
2. the capsular preparation of KW-3049 dispersion
Use above KW-3049 dispersion powder, obtain capsule according to following prescription and preparation method.
With KW-3049 dispersion powder, dextrin, lactose, sodium lauryl sulphate, carboxymethyl starch sodium mix homogeneously, under the sprinkling of 30 POVIDONE K 30 BP/USP 30 alcoholic solution, mixture is carried out pelletize, treat to add the magnesium stearate mixing again after the granule oven dry, fill is in capsule.Every piece of capsule contains granule 140mg.
Embodiment 8
1. the preparation of KW-3049 solid dispersion
Take by weighing in 50 gram poloxamers 188 and the 10 gram Macrogol 4000s heating in water bath fusion; 12 gram KW-3049 add in the above-mentioned fused mass with 30ml chloroform dissolving back, and stirring and evenly mixing continues to stir until chloroform and waves to the greatest extent, and cooling is fast pulverized, and promptly gets the solid dispersion powder of medicine.
2. the capsular preparation of KW-3049 dispersion
Use above KW-3049 dispersion powder, obtain capsule according to following prescription and preparation method.
With KW-3049 dispersion powder, mannitol, lactose, cross-linking sodium carboxymethyl cellulose mix homogeneously, under the sprinkling of 30 POVIDONE K 30 BP/USP 30 alcoholic solution, mixture is carried out pelletize, to treat to add the magnesium stearate mixing again after the granule oven dry, fill is in capsule.Every piece of capsule contains granule 140mg.
Embodiment 9
1. the preparation of KW-3049 solid dispersion
Take by weighing 44 gram polyethylene glycol 6000s in beaker, the heating in water bath fusion; 6 gram KW-3049 add in the fused polyethylene glycol 6000 after with the dissolve with ethanol of 20ml heat, and stirring and evenly mixing continues to stir until ethanol and waves to the greatest extent, and cooling is fast pulverized, and promptly gets the solid dispersion powder of medicine.
2. the capsular preparation of KW-3049 dispersion
Use above KW-3049 dispersion powder, obtain capsule according to following prescription and preparation method.
With KW-3049 dispersion powder, dextrin, lactose, poloxamer 188, Brij-35 mix homogeneously, under the sprinkling of hydroxypropyl methylcellulose aqueous solution, mixture is carried out pelletize, treat to add the magnesium stearate mixing again after the granule oven dry, fill is in capsule.Every piece of capsule contains granule 140mg.
Embodiment 10
1. the preparation of KW-3049 solid dispersion
Take by weighing 25 gram polyvinylpyrrolidones and 5 gram KW-3049 in beaker, add dehydrated alcohol 100ml, heating in water bath stirs until dehydrated alcohol and waves to the greatest extent to dissolving fully, and cooling is fast pulverized, and promptly gets the solid dispersion powder of medicine.
2. the preparation of the tablet of KW-3049 dispersion
Use above KW-3049 dispersion powder, obtain tablet according to following prescription and preparation method.
With KW-3049 dispersion powder, dextrin, corn starch, sodium lauryl sulphate, carboxymethyl starch sodium mix homogeneously, under the sprinkling of hydroxypropyl methylcellulose aqueous solution, mixture is carried out pelletize, treat to add the Pulvis Talci mixing again after the granule oven dry, tabletting in single punch tablet machine, hardness 40N, the heavy 140mg of sheet.
Embodiment 11
1. the preparation of KW-3049 solid dispersion
Take by weighing 22 gram citric acid, 8 gram erythritols, 10 gram carbamide and 2 gram mannitol in beaker, the heating in water bath fusion; 8 gram KW-3049 add in the above-mentioned fused mass after with the anhydrous alcohol solution of 30ml heat, and stirring and evenly mixing continues to stir until dehydrated alcohol and waves to the greatest extent, and cooling is fast pulverized, and promptly gets the solid dispersion powder of medicine.
2. the capsular preparation of KW-3049 dispersion
Use above KW-3049 dispersion powder, obtain capsule according to following prescription and preparation method.
With KW-3049 dispersion powder, lactose, potato starch, Brij-35, cross-linking sodium carboxymethyl cellulose mix homogeneously, under the sprinkling of 30 POVIDONE K 30 BP/USP 30 alcoholic solution, mixture is carried out pelletize, treat to add the magnesium stearate mixing again after the granule oven dry, fill is in capsule.Every piece of capsule contains granule 140mg.
Embodiment 12
1. the preparation of KW-3049 solid dispersion
Take by weighing 52 gram polyethylene glycol 6000s in beaker, the heating in water bath fusion; 3 gram KW-3049 are added in the fused polyethylene glycol 6000, stir until medicine dissolution, cooling is fast pulverized, and promptly gets the solid dispersion powder of medicine.
2. the capsular preparation of KW-3049 dispersion
Use above KW-3049 dispersion powder, obtain capsule according to following prescription and preparation method.
With KW-3049 dispersion powder, mannitol, lactose, poloxamer 188, carboxymethyl starch sodium mix homogeneously, under the sprinkling of hydroxypropyl methylcellulose aqueous solution, mixture is carried out pelletize, treat to add the micropowder silica gel mixing again after the granule oven dry, fill is in capsule.Every piece of capsule contains granule 140mg.
Embodiment 13
1. the preparation of KW-3049 solid dispersion
Take by weighing 33 gram Macrogol 4000s in beaker, the heating in water bath fusion; 7 gram KW-3049 add in the fused Macrogol 4000 with 20ml acetone and 10ml chloroform dissolving back, and stirring and evenly mixing continues to stir until organic solvent and waves to the greatest extent, and cooling is fast pulverized, and promptly gets the solid dispersion powder of medicine.
2. the capsular preparation of KW-3049 dispersion
Use above KW-3049 dispersion powder, obtain capsule according to following prescription and preparation method.
With KW-3049 dispersion powder, mannitol, lactose mix homogeneously, under the sprinkling of 30 POVIDONE K 30 BP/USP 25 and hydroxypropyl cellulose solution, mixture is carried out pelletize, treat that granule oven dry back fill is in capsule.Every piece of capsule contains granule 140mg.
Embodiment 14
1. the preparation of KW-3049 solid dispersion
Take by weighing 30 gram polyethylene glycol 6000s and 10 gram poloxamers 188 in beaker, the heating in water bath fusion; 2 gram KW-3049 are added in the fused mass, stir until medicine dissolution, cooling is fast pulverized, and promptly gets the solid dispersion powder of medicine.
2. the particulate preparation of KW-3049 dispersion
Use above KW-3049 dispersion powder, obtain granule according to following prescription and preparation method.
With KW-3049 dispersion powder, mannitol, calcium hydrogen phosphate, Brij-35, citric acid, sodium bicarbonate mix homogeneously, under the sprinkling of 30 POVIDONE K 30 BP/USP 25 alcoholic solution, mixture is carried out pelletize, treat to add the micropowder silica gel mixing again after the granule oven dry, be sub-packed in the packaging bag.Every bag contains granule 10g.
Embodiment 15
1. the preparation of KW-3049 solid dispersion
Take by weighing 35 gram polyvinylpyrrolidones and 5 gram KW-3049 in beaker, add the 200ml chloroform, stir until dissolving, stir on heating in water bath limit, limit, and chloroform is waved to the greatest extent, and cooling is fast pulverized, and promptly gets the solid dispersion powder of medicine.
2. the capsular preparation of KW-3049 dispersion
Use above KW-3049 dispersion powder, obtain capsule according to following prescription and preparation method.
With KW-3049 dispersion powder, microcrystalline Cellulose, dextrin, sodium lauryl sulphate, Brij-35 mix homogeneously, under the sprinkling of 30 POVIDONE K 30 BP/USP 30 alcoholic solution, mixture is carried out pelletize, treat to add the micropowder silica gel mixing again after the granule oven dry, fill is in capsule.Every piece of capsule contains granule 140mg.
Embodiment 16
1. the preparation of KW-3049 solid dispersion
Take by weighing 80 gram polyethylene glycol 6000s and 40 gram KW-3049 in beaker, add the 200ml tert-butyl alcohol, be stirred to dissolving fully, heating in water bath limit, limit is stirred until the tert-butyl alcohol and is waved to the greatest extent, and cooling is fast pulverized, and promptly gets the solid dispersion powder of medicine.
2. the particulate preparation of KW-3049 dispersion
Use above KW-3049 dispersion powder, obtain granule according to following prescription and preparation method.
With KW-3049 dispersion powder, lactose, wheaten starch, sodium lauryl sulphate mix homogeneously, under the sprinkling of 30 POVIDONE K 30 BP/USP 30 alcoholic solution, mixture is carried out pelletize, treat to add Pulvis Talci and magnesium stearate mixing again after the granule oven dry, be sub-packed in the packaging bag.Every bag contains granule 10g.
Come the external stripping situation of KW-3049 preparation more of the present invention and ordinary preparation below by dissolution test.
Dissolution test
The preparation of test specimen: KW-3049 formulation samples of the present invention adopts the preparation of preparation among embodiment 1, embodiment 2, the embodiment 3; Ordinary preparation also prepares three kinds, the capsular preparation method of KW-3049 solid dispersion in the reference example 1,2,3, and except that drug use KW-3049 crude drug, other composition and preparation method are respectively with embodiment 1,2,3.
Leaching condition: dissolving-out method adopts the device of dissolution method (two appendix X of Chinese Pharmacopoeia version in 2010 C) first method; Dissolution medium is the pH6.8 phosphate buffer that contains 0.2% sodium lauryl sulphate, and the medium volume is 900ml, and medium temperature is 37 ℃, rotating speed 50rpm; Sampling in the 10th, 20,30,45,60 minute after on-test.
Content assaying method: adopt high performance liquid chromatography, analytical column is Diamonsil C
18Analytical column (5 μ, 4.6mm * 250mm); Mobile phase is 0.05M potassium dihydrogen phosphate aqueous solution-acetonitrile (60: 40), and the detection wavelength is 237nm, 30 ℃ of column temperatures, flow velocity 1.000ml/min.
Experimental result is as follows:
From The above results as can be seen, preparation of the present invention is basic release fully at 30 minutes, and ordinary preparation just discharged about half at 60 minutes.More than experiment shows the stripping fast of the medicine in the preparation of the present invention.
Claims (9)
1. a KW-3049 solid preparation comprises KW-3049, solid dispersion carrier and functional adjuvant, and its component and proportioning are as follows:
Constituent content (gram/gram)
KW-3049 0.01-30%;
Solid dispersion carrier 0.01-60%;
Functional adjuvant surplus;
Wherein,
The solid dispersion carrier is selected from one or more in Macrogol 4000, polyethylene glycol 6000, polyvinylpyrrolidone, pluronic F68, carbamide, citric acid, mannitol, xylitol, sorbitol and the erythritol;
Functional adjuvant comprises hydrophilic filler, wetting agent, disintegrating agent, binding agent and fluidizer.
2. by the described KW-3049 solid preparation of claim 1, it is characterized in that said proportioning is as follows:
Constituent content (gram/gram)
KW-3049 0.1-10%;
Solid dispersion carrier 1-50%;
Functional adjuvant surplus.
3. by claim 1 or 2 described KW-3049 solid preparations, it is characterized in that said component is as follows:
The solid dispersion carrier is selected from one or more in Macrogol 4000, polyethylene glycol 6000 and the polyvinylpyrrolidone;
Functional adjuvant comprises hydrophilic filler, wetting agent, disintegrating agent, binding agent and fluidizer.
4. by claim 1 or 2 or 3 described KW-3049 solid preparations, the hydrophilic filler in the functional adjuvant includes but not limited to starch based, starch derivatives, dextrin, inorganic salts, saccharide, sugar alcohols, cellulose family and cellulose derivative.
5. by claim 1 or 2 or 3 described KW-3049 solid preparations, the wetting agent in the functional adjuvant is selected from one or more in sodium lauryl sulphate, polyoxyethylene castor oil, tween 20, Tween-60, tween 80, poloxamer 188, soybean lecithin, Ovum Gallus domesticus Flavus lecithin and the Brij-35.
6. by claim 1 or 2 or 3 described KW-3049 solid preparations, the disintegrating agent in the functional adjuvant includes but not limited to cellulose family, cellulose derivative, starch based, starch derivatives, polyvinylpolypyrrolidone and gas-producing disintegrant.
7. by claim 1 or 2 or 3 described KW-3049 solid preparations, the binding agent in the functional adjuvant includes but not limited to cellulose family, cellulose derivative and polyvidone.
8. by claim 1 or 2 or 3 described KW-3049 solid preparations, the fluidizer in the functional adjuvant is selected from one or more in magnesium stearate, micropowder silica gel and the Pulvis Talci.
9. the described KW-3049 solid preparation of claim 1 to 8, its preparation method is as follows:
(1) KW-3049 is added in the fused solid dispersion carrier after by suitable organic solvent dissolution, stir until organic solvent and wave to the greatest extent, pulverize the cooling back fast; Or directly KW-3049 is added in the fused solid dispersion carrier and to stir until medicine dissolution, cooling is fast pulverized then; Or KW-3049 and solid dispersion carrier be dissolved in the suitable organic solvent, wave most organic solvent then, pulverize;
(2) said medicine dispersion powder and functional adjuvant are prepared into granule by certain prilling process, gained granule directly packing is granule, and fill is capsule in capsule, also the gained granule can be pressed into tablet.
Used organic solvent is selected from one or more in ethanol, acetone, chloroform or the tert-butyl alcohol in the preparation process; Used prilling process does not limit its kind.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010101972572A CN102266337A (en) | 2010-06-04 | 2010-06-04 | Benidipine hydrochloride solid preparation and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010101972572A CN102266337A (en) | 2010-06-04 | 2010-06-04 | Benidipine hydrochloride solid preparation and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102266337A true CN102266337A (en) | 2011-12-07 |
Family
ID=45048922
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010101972572A Pending CN102266337A (en) | 2010-06-04 | 2010-06-04 | Benidipine hydrochloride solid preparation and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102266337A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1370532A (en) * | 2001-02-20 | 2002-09-25 | 四川巴中普瑞制药有限公司 | Maleic amlodipine besylate tablet as cardiovascular disease treating medicine and its prepn |
| CN1951373A (en) * | 2006-10-26 | 2007-04-25 | 徐竹青 | Method for preparing nimodipine dispersible tablet with high dissolution |
| CN101068546A (en) * | 2004-10-06 | 2007-11-07 | 卫材R&D管理有限公司 | Medicinal composition, process for producing the same, and method of stabilizing dihydropyridine compound in medicinal composition |
-
2010
- 2010-06-04 CN CN2010101972572A patent/CN102266337A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1370532A (en) * | 2001-02-20 | 2002-09-25 | 四川巴中普瑞制药有限公司 | Maleic amlodipine besylate tablet as cardiovascular disease treating medicine and its prepn |
| CN101068546A (en) * | 2004-10-06 | 2007-11-07 | 卫材R&D管理有限公司 | Medicinal composition, process for producing the same, and method of stabilizing dihydropyridine compound in medicinal composition |
| CN1951373A (en) * | 2006-10-26 | 2007-04-25 | 徐竹青 | Method for preparing nimodipine dispersible tablet with high dissolution |
Non-Patent Citations (1)
| Title |
|---|
| 宗莉等: "用二元载体固体分散技术提高尼索地平溶出度和调节溶出速率", 《中国药学杂志》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102793680A (en) | Azilsartan solid dispersion and preparation method and medicinal composition thereof | |
| EP3003277B1 (en) | Process for the preparation of a pharmaceutical composition comprising rivaroxaban | |
| EP2165702B1 (en) | Stable and readily dissolved compositions of candesartan cilexetil prepared with wet granulation | |
| CN101816637A (en) | Leflunomide tablet preparation and preparation method thereof | |
| CN101773498A (en) | Oral slow/controlled-release preparation containing febuxostat and preparation method thereof | |
| CN102266330A (en) | Cilnidipine preparation and preparation method thereof | |
| EP2050436A1 (en) | Pharmaceutical composition containing dutasteride | |
| CN102349877A (en) | Hydroxychloroquine sulfate capsule, hydroxychloroquine sulfate dispersible tablet and application thereof | |
| CN100486568C (en) | Loxoprofen sodium sustained release preparation | |
| NZ543337A (en) | Stable compositions of atorvastatin prepared with wet granulation | |
| CN106619646B (en) | A kind of preparation method of tegafur, gimeracil and oteracil potassium composition | |
| CN102266337A (en) | Benidipine hydrochloride solid preparation and preparation method thereof | |
| CN102349889B (en) | Composition containing dronedarone | |
| CN102846573A (en) | Silibinin double-layer slow-release tablets and preparation method thereof | |
| CN104415034A (en) | Imidafenacin pharmaceutical composition and preparation method thereof | |
| CN106606505A (en) | Tofogliflozin pharmaceutical composition and preparation method thereof | |
| CN104784135A (en) | Finasteride tablets | |
| CN104382859B (en) | A kind of SLGT2 inhibitor particle and preparation method thereof | |
| CN106913537B (en) | Abiraterone acetate sublingual tablet and preparation method thereof | |
| CN106913538B (en) | Abiraterone acetate sublingual tablet and preparation method thereof | |
| CN103284952A (en) | Medical composition containing fenofibrate | |
| CN102166212A (en) | Method for making benidipine hydrochloride quickly dissolved from tablets | |
| CN101103964B (en) | Sustained-release preparation containing felodipine and preparation method thereof | |
| JPH04159222A (en) | Production of solid preparation for oral administration | |
| JPS618A (en) | Nifedipin-containing drug preparation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20111207 |