CN1915225A - Drop pills of Amlodipine, and preparation method - Google Patents
Drop pills of Amlodipine, and preparation method Download PDFInfo
- Publication number
- CN1915225A CN1915225A CN 200610080743 CN200610080743A CN1915225A CN 1915225 A CN1915225 A CN 1915225A CN 200610080743 CN200610080743 CN 200610080743 CN 200610080743 A CN200610080743 A CN 200610080743A CN 1915225 A CN1915225 A CN 1915225A
- Authority
- CN
- China
- Prior art keywords
- amlodipine
- drop pill
- preferred
- preparation
- drop
- 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
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
A dripping pill of amlodipine salt is prepared from the organic acid's salt of amlodipine and medicinal additive through adding amlodipine to fused medicinal additive, stirring, dripping, in condensing agent and drying.
Description
Technical field
The present invention relates to a kind of resisting hypertension, angina drug drop pills of amlodipine novel form and preparation method thereof, belong to technical field of medicine.
Technical background
Amlodipine (Amlodipine), claim Amlodipine, Norvasc, amlodipine, Amlodipine Besylate Tablet again, its chemistry is by name: 3-ethyl-5-methyl-2-(the amino ethoxymethyl of 2-)-4-(2-chlorphenyl)-1,4-dihydro-6-methyl-3, the 5-pyridine dicarboxylate, molecular formula: C
20H
25N
2O
5Cl, the addition salts of pharmaceutically acceptable acids such as its benzenesulfonic acid commonly used, maleic acid.It is a dihydropyridine type calcium antagonists, has loose vascular smooth muscle, coronary artery dilator and small artery on every side, coronary blood flow increasing, reduce peripheral vascular resistance, improve the pharmacological action of cardiac muscle, be usually used in various types of hypertension and angina pectoris prevention and treatment of diseases clinically, be particularly useful for nitrate and the beta-blocker quasi drugs person of failing to respond to any medical treatment to the toleration of ischemia.This product oral administration post-absorption is complete, and duration of efficacy is long, and the user makes, and every day, medication once got final product, but its weak point is to absorb slowly, reaches the blood drug level peak in 6～12 hours after the administration, single oral 5mg, and blood medicine peak value is 3.0ng/ml; Single oral 10mg, blood medicine peak value is 5.9ng/ml.Absolute bioavailability is 64%-90%.Consider this class disease of patient characteristics, be badly in need of the exploitation quick-effective preparation.
Being used for clinical amlodipine product at present comprises: amlodipine besylate tablets, amlodipine maleate sheet and Levamlodipine beaylate tablets.Do not see patent and the document that drops is arranged both at home and abroad.
Amlodipine has 28 in Chinese patents, and majority is the technology patent of chemosynthesis; There are 5 with the relevant patent of amlodipine dosage form: (1) Chinese application number 01107141.9, maleic amlodipine besylate tablet as cardiovascular disease treating medicine and preparation method thereof; (2) Chinese application number 200310111141.2, Amlodipine Besylate Tablet oral cavity disintegration tablet and preparation method thereof; (3) Chinese application number 200410003035.7, amido chloro diping dispersion tablet and preparation method thereof; (4) Chinese application number 200410018848.3, amlodipine besylate sustained-release capsules and preparation method thereof; (5) Chinese application number 200410032054.2, treatment hypertension, anginal Levamlodipine Besylate oral cavity disintegration tablet and preparation method.
Above-mentioned patent is all irrelevant with the invention of present patent application.
Summary of the invention
The object of the present invention is to provide oral administration dripping pill (hereinafter to be referred as drop pills of amlodipine) of a kind of amlodipine acylate and preparation method thereof, to increase clinical pharmaceutical dosage form, overcome sheet and absorb shortcoming slowly, and the performance drop pill absorbs the dosage form advantage fast, that bioavailability is high, reach the raising bioavailability, bring into play quick-acting therapeutical effect, reduce toxic and side effects.Buccal is the vascularity that utilizes the oral cavity abundant, make medicine be absorbed into blood rapidly, reach the required blood drug level of antitumor, most medicines are swallowed and are entered in the body in the time of buccal, the purpose of quick-acting (buccal) can be reached like this, long lasting purpose (most medicines swallow enter digestive system absorb) can be reached again.Medicinal adjuvant in the drop pill has good peptizaiton, can make medicine reach nanometer and micron-sized dispersion, reduces the chance of intermolecular collision, reaches the purpose that improves bioavailability.Another object of the present invention provides the preparation method of ring drop pills of amlodipine novel form.
The specific embodiment
For achieving the above object, the present invention is implemented by following technical proposals.
1, the resulting drop pill of the present invention comprises following composition
Medicine of the present invention is the drop pill of being made by following component;
Pharmaceutical formulation:
Amlodipine 2%～40% (W/W)
Medicinal adjuvant 60%～98% (W/W)
In drop pills of amlodipine, the amount of amlodipine is 2%～40% (W/W) of drop pill gross weight; Preferred 5%～30% (W/W); Medicinal adjuvant is formed for one or more pharmaceutic adjuvants, accounts for 60%～98% (W/W) of drop pill gross weight.
Medicinal adjuvant drop pill substrate, surfactant (contain or do not contain), cosolvent (contain or do not contain).Drop pill substrate is meant one or more the compositions in the Polyethylene Glycol (PEG), Myrj 45, sodium stearate, glycerin gelatine, stearic acid, glyceryl monostearate, hydrogenated vegetable oil, insect wax of molecular weight 〉=1500.The compositions of preferred Polyethylene Glycol-4000, Polyethylene Glycol-6000 and different proportion thereof.The best is the compositions of PEG-4000 and PEG-6000.Wherein yet can not contain or contain other does not influence drop pill substrate on a small quantity and returns other solid-state adjuvants at normal temperatures, as surfactant poloxamer, dodecyl sodium sulfate, carboxymethyl starch sodium (CMS-Na) and tween 80 etc., preferred tween 80 and CMS-Na; These adjuvants help dispersion, stripping, uniformity and the stability of medicine.Also can use or not use some cosolvents, as ethanol, propylene glycol, glycerol, liquid macrogol, preferred alcohol.
2, the resulting drop pill of the present invention prepares by following method
The present invention adopts following preparation method:
(1) preparation of amlodipine-PEG fused solution
Method 1: take by weighing medicinal adjuvant by formula ratio, wherein can also add other pharmaceutic adjuvants such as the tween 80 that help the drop pill Chinese medicine to discharge, CMS-Na etc., heat fused, the amlodipine of adding formula ratio fully stirs and makes its complete fusion, be uniformly dispersed, make fused solution.Perhaps,
Method 2: take by weighing the amlodipine medicine by formula ratio, add an amount of cosolvent, after the slight fever dissolving, be added in the medicinal adjuvant fused solution of formula ratio, mix, volatilize cosolvent, after being uniformly dispersed, make fused solution.
(2) preparation of drop pill
Above-mentioned fused solution is put in the surge drum of drop pill machine, insulation splashes in condensed fluid proper temperature under with certain speed of dripping, and is condensed into ball, and the collection drop pill is removed coolant, and drying can obtain the finished product of medicine.It is simple that this preparation method has technology, adjuvant cheapness, the production characteristics that wait easy to control the quality.
The quality standard of raw material amlodipine meets the requirement of China national drug standard in the prescription of medicine of the present invention.
In the preparation method of medicine of the present invention, liquid Paraffin, methyl-silicone oil, vegetable oil, kerosene all can be used as condensed fluid, are preferably liquid Paraffin, methyl-silicone oil.During as condensed fluid, the drop pill roundness is better with liquid Paraffin or methyl-silicone oil, size evenly, smooth surface, solid colour.The results are shown in Table 1.
The different condensing droplet system results of table 1
| Condensed fluid | Liquid Paraffin | Methyl-silicone oil | Vegetable oil | Kerosene |
| The drop pill mouldability | Formability is good | Formability is good | Formability is poor | Formability is good |
| The drop pill shape | Spheroidal | Spheroidal | Lamellar | Oblate spheroid |
| With the principal agent dissolubility | Do not dissolve | Do not dissolve | Do not dissolve | Do not dissolve |
In the preparation method of medicine of the present invention, these two kinds of methods of fusion method and solvent-fusion method all can be used as the method for making drop pill, but the preferred molten method.
The uniformity of dosage units that studies have shown that fusion method and solvent-fusion method all meets the pharmacopeia regulation.But the operation of solvent-fusion method is more numerous and diverse, is difficult for determining in the fused solution whether emptying of ethanol, the difficult control of commercial production; From appearance luster, the drop pill color that fusion method and solvent-fusion method are made all is off-white color, and size is even, smooth surface, solid colour.Take all factors into consideration the preferred molten method.
In the preparation method of medicine of the present invention, the holding temperature of fused solution is 60 ℃～110 ℃, is preferably 70 ℃～95 ℃, and the best is 75～90 ℃.
In making the process of amlodipine-PEG fused solution, need constantly to stir, make it become homogeneous phase, can contain air in certain amount in the fused solution this moment, should exclude air in drop pill production, otherwise will influence the roundness of drop pill.Therefore, after fused solution makes, must insulation place a period of time, the air in the fused solution is got rid of totally fully.Amlodipine-PEG fused solution is incubated 20,25,30 minutes respectively under 80 ℃, drips the system drop pill then respectively, whether the surface of observing drop pill has plaque, to determine best temperature retention time.Found that, there is a small amount of very little plaque on the drop pill surface that is incubated 20,25 minutes molten melt drop system, show that being incubated 20,25 minutes bubbles does not catch up with only fully: be incubated the drop pill smooth surface of 30 minutes molten melt drop system, no plaque shows fused solution Ex-all fully after 30 minutes.
Therefore, in the preparation method of medicine of the present invention, the temperature retention time of fused solution is at least 20 minutes, is preferably at least 30 minutes.
Fused solution has a little hangover when water dropper drips, and when moving, fused solution then may bring the sub-fraction air into again in air, if the condensed fluid upper temp is too low, then hangover has little time withdrawal, air has little time to discharge fused solution and promptly solidifies, influences shaped degree of drop pill and surface flatness.Condensed fluid lower floor temperature is too high, and the fused solution condensation is incomplete, and drop pill can also influence the drop pill roundness in condensate line bottom adhesion.Through overtesting, upper strata condensed fluid height should be controlled at about 20cm to well, and following layer height is good with 30cm, and under this height, the drop pill condensation is complete, good moldability, adhesion.
Therefore, in the preparation method of medicine of the present invention, the temperature on condensed fluid top is 10～45 ℃, 15～35 ℃ of preferred temperature, 20～30 ℃ of optimum temperatures; The temperature of condensed fluid bottom is-10～10 ℃: preferred temperature-5～5 ℃, optimum temperature-3～3 ℃.Top condensed fluid height is preferably 10～35cm, preferred heights 15～30cm, optimum height 20cm; Bottom condensed fluid height is preferably 20～40cm, preferred heights 25～35cm, optimum height 30cm.
The present invention investigates dripping factors such as speed, a distance.In the preparation method of medicine of the present invention, drip apart from being 2～8cm, dripping speed is 10～100 droplets/minute; Be preferably and drip apart from 2～5cm, dripping speed is 30～70 droplets/minute.
Can find out the advantage of drop pill of the present invention from table 2.General about 5 minutes of drop pill dissolve scattered time limit of the present invention, (＞25min) molten loosing rapidly shortened the time that entering performance drug effect in the body than tablet.
The dissolve scattered time limit of table 2 amlodipine besylate tablets and drop pill of the present invention relatively
| Sample number into spectrum | 1 | 2 | 3 | 4 | 5 | 6 |
| Amlodipine besylate tablets min | 27 | 28 | 29 | 30 | 25 | 26 |
| Amlodipine besylate dropping pills lot number 040906 min | 4.5 | 4.6 | 4.7 | 4.5 | 4.7 | 4.6 |
Amlodipine is indissoluble in water, so the salifiable form of the general preparation of medicine mainly contains acylates such as benzene sulfonate, maleate, mesylate, camsilate.The present invention makes drop pill with the amlodipine acylate, take the back its to melt diffusing property better than tablet; And make drop pill, can swallow, can be dispersed with very soon under one's belt and be beneficial to gastrointestinal absorption.Can containing, more help the absorption of this product by the liposoluble passage of oral mucosa, directly enter blood circulation, onset in 5 minutes arrives drug effect fast, and effect more is better than other oral formulations.
In addition, amlodipine acylate drop pill of the present invention also has following advantage: volume is little, taking convenience (once a day, each ball), is easy to be accepted by the patient; Production process is few, and the cycle is short, the automaticity height, and the production efficiency height, cost is low, is easy to industrialization; The drop pill working condition is easy to control, and the ball method of double differences is different little, and content is more accurate, and quality is guaranteed; The bioavailability height of most critical, toxic and side effects is little; This dosage form is one of dosage form of country's recommendation at present.
3, the route of administration of the resulting drop pills of amlodipine of the present invention
The route of administration of drop pills of amlodipine is meant in various treatment for cancer to be used buccal and or swallows.According to the disease that gives object, body weight and the state of an illness, give dosage usually in 1mg～100mg/ days scope.
The following examples are used to further specify the present invention, but they are not to attempt in office where face limits the scope of the invention.
Embodiment 1
Prescription (specification: the 2.5mg/ ball)
Amlodipine Besylate Tablet 2.5g
Polyethylene glycol 6000 15g
Macrogol 4000 15g
Make 1000 altogether
Preparation method:
Prescription ratio in each component is weighed, and Polyethylene Glycol heating is made it fusion, adds the Amlodipine Besylate Tablet powder, and constantly stirring makes whole fusions, puts in the reservoir of drop pill machine, and 80 ℃ of insulations 30 minutes are stand-by.Adjust and drip apart from being 3cm, at the uniform velocity splash in the liquid paraffin condensed fluid that contains methyl-silicone oil with 50 droplets/minute the speed of dripping, the temperature of condensed fluid top 20cm is 20 ± 2 ℃, and the temperature of bottom 30cm is 0 ± 1 ℃.Collect drop pill, remove the condensing agent on drop pill surface, drying is selected ball, gets product.
Molten diffusing timing: six batch samples that go out with above-mentioned prescription and explained hereafter are carried out molten diffusing timing, measurement result such as following table according to an appendix X11 of Chinese Pharmacopoeia version in 2000 A the 3rd method.
The molten diffusing timing result (second) of table 36 batch samples
| Lot number | 040906-1 | 040906-2 | 040907-1 | 040907-2 | 040908-1 | 040908-2 |
| The 1st ball | 249 | 252 | 263 | 258 | 246 | 248 |
| The 2nd ball | 253 | 259 | 261 | 243 | 244 | 257 |
| The 3rd ball | 255 | 247 | 261 | 258 | 249 | 256 |
| The 4th ball | 270 | 268 | 271 | 266 | 253 | 254 |
| The 5th ball | 274 | 244 | 256 | 253 | 268 | 270 |
| The 6th ball | 271 | 263 | 262 | 254 | 257 | 249 |
The result shows that prepared amlodipine besylate dropping pills all has the molten faster diffusing time.
Embodiment 2
Prescription (specification: the 5mg/ ball)
Amlodipine Besylate Tablet 5g
Polyethylene glycol 6000 30g
Tween 80 0.25g
Make 1000
Preparation method:
Prescription ratio in each component is weighed, and Polyethylene Glycol heating is made it fusion, adds Amlodipine Besylate Tablet fine powder and tween 80, and constantly stirring makes whole fusions, puts in the reservoir of drop pill machine, and 85 ℃ of insulations 30 minutes are stand-by.Adjust and drip apart from being 3cm, at the uniform velocity splash in the liquid paraffin condensed fluid with 60 droplets/minute the speed of dripping, the temperature of condensed fluid top 20cm is 23 ± 3 ℃, and the temperature of bottom 30cm is 5 ± 1 ℃.Collect drop pill, remove the condensing agent on drop pill surface, drying is selected ball, gets product.
Embodiment 3
Prescription (specification: the 2.5mg/ ball)
Amlodipine Besylate Tablet 2.5g
Polyethylene glycol 6000 5g
Macrogol 4000 25g
Make 1000
Preparation method:
Method for making is with embodiment 1.
Embodiment 4
Prescription (specification: the 2.5mg/ ball)
Amlodipine maleate 2.5g
Polyethylene glycol 6000 15g
Macrogol 4000 15g
Make 1000
Preparation method:
Method for making is with embodiment 1.
Embodiment 5
Prescription (specification: the 2.5mg/ ball)
Levamlodipine besylate 2.5g
Polyethylene glycol 6000 15g
Macrogol 4000 15g
Make 1000
Preparation method:
Method for making is with embodiment 1.
Embodiment 6
Prescription (specification: the 2.5mg/ ball)
Amlodipine Besylate Tablet 2.5g
Polyethylene glycol 6000 30g
Stearic acid 2.5g
Make 1000
Preparation method:
Prescription ratio in each component is weighed, and the heating of polyethylene glycol 6000 and stearic acid is made it fusion, adds the amlodipine fine powder, and constantly stirring makes whole fusions, puts in the reservoir of drop pill machine, and 80 ℃ of insulations 30 minutes are stand-by.Adjust and drip apart from being 3cm, at the uniform velocity splash in the methyl-silicone oil condensed fluid with 55 droplets/minute the speed of dripping, the temperature on condensed fluid top is 20 ± 2 ℃, and the temperature of bottom is 0 ± 1 ℃.Collect drop pill, remove the condensing agent on drop pill surface, drying is selected ball, gets product.
Embodiment 7
Prescription (specification: the 2.5mg/ ball)
Amlodipine Besylate Tablet 2.5g
Macrogol 4000 30g
Carboxymethyl starch sodium 2.5g
Make 1000
Preparation method:
Amlodipine adds an amount of dehydrated alcohol, after slight fever makes dissolving, is added on fused Macrogol 4000 and CMS-Na, constantly stirs, and volatilizes ethanol, put in the reservoir of drop pill machine, 85 ℃ the insulation 30 minutes stand-by.Adjust and drip apart from being 4cm, at the uniform velocity splash in the liquid Paraffin condensed fluid with 50 droplets/minute the speed of dripping, the temperature on condensed fluid top is 20 ± 2 ℃, and the temperature of bottom is 0 ± 1 ℃.Collect drop pill, remove the condensing agent on drop pill surface, drying is selected ball, gets product.
Embodiment 8
Prescription (specification: the 2.5mg/ ball)
Amlodipine Besylate Tablet 2.5g
Polyethylene glycol 6000 30g
Glyceryl monostearate 2.5g
Make 1000
Preparation method:
Ten thousand ratios of locating in each component are weighed, and the heating of Polyethylene Glycol and glyceryl monostearate is made it fusion, add the amlodipine fine powder, and constantly stirring makes whole fusions, put in the reservoir of drop pill machine, and 80 ℃ of insulations 30 minutes are stand-by.Adjust and drip apart from being 4cm, at the uniform velocity splash in the kerosene condensed fluid with 60 droplets/minute the speed of dripping, the temperature on condensed fluid top is 20 ± 2 ℃, and the temperature of bottom is 0 ± 1 ℃.Collect drop pill, remove the condensing agent on drop pill surface, drying is selected ball, gets product.
Embodiment 9
Prescription (specification: the 2.5mg/ ball)
Amlodipine Besylate Tablet 2.5g
Macrogol 4000 17.5g
Make 1000
Preparation method:
Method for making is with embodiment 1.
Embodiment 10
Prescription (specification: the 2.5mg/ ball)
Levamlodipine besylate 2.5g
Polyethylene glycol 6000 22.5g
Make 1000 altogether
Preparation method:
Method for making is with embodiment 1.
Embodiment 11
Prescription (specification: the 5mg/ ball)
Amlodipine Besylate Tablet 5g
Macrogol 4000 19g
Glycerin gelatine 1g
Make 1000 altogether
Preparation method:
Weight proportion by each component is weighed, and Polyethylene Glycol, glycerin gelatine heating are made it fusion, adds the Amlodipine Besylate Tablet fine powder, and other method for making is with embodiment 1.
Embodiment 12
Prescription (specification: the 2.5mg/ ball)
Amlodipine Besylate Tablet 2.5g
Macrogol 4000 27.5g
Glycerin gelatine 1g
Hydrogenated vegetable oil 0.7g
Poloxamer 0.3g
Make 1000 altogether
Preparation method:
Weight proportion by each component is weighed, and Polyethylene Glycol, glycerin gelatine, hydrogenated vegetable oil, poloxamer heating are made it fusion, adds the Amlodipine Besylate Tablet fine powder, and other method for making is with embodiment 1.
Embodiment 13
Prescription (specification: the 2.5mg/ ball)
Amlodipine mesylate 2.5g
Macrogol 4000 18g
Polyethylene glycol 6000 18g
Make 1000 altogether
Preparation method:
Method for making is with embodiment 1.
Embodiment 14
Reference literature [Xing Xiangfei etc., the RP-HPLC method of Levamlodipine analyze and at rabbit body giving drugs into nose for dynamics research, Central China University of Science and Technology's journal (medicine), 2002; 31 (6): 623] Chinese medicine is pressed 5mg/kg dosage and is irritated stomach amlodipine besylate tablets (pfizer inc production) and drop pill (self-control, lot number 040906-1), comparative result such as table 4 once for 4 healthy rabbits for dynamical investigation method.
The main pharmacokinetic parameter of table 4 amlodipine besylate tablets and drop pill relatively
| Main medicine generation technique parameter | Amlodipine besylate dropping pills | Amlodipine besylate tablets |
| t max h | 0.4±0.1 | 3.4±0.6 |
| C max ng/ml | 29.04±2.12 | 25.04±3.18 |
| t 1/2 h | 6.26±1.14 | 5.95±1.87 |
| AUC 0～∞ ng·h/ml | 263.8±18.14 | 198.6±29.12 |
Illustrate medicine with drops can be very fast reach the blood drug level peak, and medicine longer duration in vivo, bioavailability is higher than conventional tablet.
Though the medicine codes or data of these data and human body has a certain distance (oral post-absorption fully but slowly, to reach peak concentration in 6～12 hours.Single oral 5mg, blood medicine peak value is 3.0ng/ml), but the effect characteristics and the trend of medicine also can have been reflected.
Claims (9)
1. the drop pill of an amlodipine acylate is characterized in that it is the drop pill that is prepared from according to a certain percentage by amlodipine acylate and medicinal adjuvant.
2. a drop pill as claimed in claim 1 is characterized in that this drop pill ball heavily is 10mg～60mg; Preferred 20mg～50mg; More preferably 25～45mg.
3. amlodipine acylate in the drop pill according to claim 1, it is characterized in that comprising the spendable acylates of pharmacy such as amlodipine, Amlodipine Besylate Tablet, Levamlodipine besylate, amlodipine maleate, Amlodipine mesylate, preferred Amlodipine Besylate Tablet, Levamlodipine besylate and amlodipine maleate.
4. one kind as the described medicinal dropping ball of claim 1～3, it is characterized in that the amount of the amlodipine that comprises in this drop pill is 5%～40% (W/W) of drop pill gross weight; Preferred 5%～20% (W/W); Medicinal adjuvant is formed for one or more pharmaceutic adjuvants, accounts for 60%～95% (W/W) of drop pill gross weight.
5. according to the preparation method of the described drop pills of amlodipine of claim 1～4, it is characterized in that preparing with the following method.
(1) preparation of fused solution
Method 1: take by weighing each medicinal adjuvant in the prescription by formula ratio, heat fused adds the amlodipine of formula ratio, fully stirs its fusion or suspendible are uniformly dispersed, and makes fused solution; Perhaps
Method 2: take by weighing amlodipine by formula ratio, add an amount of cosolvent, after the slight fever dissolving, be added in the medicinal adjuvant fused solution of formula ratio, mix, volatilize cosolvent, after being uniformly dispersed, make fused solution;
(2) preparation of drop pill
Fused solution is put in the surge drum of drop pill machine, insulation with certain dripping in the fast condensed fluid that splashes under the proper temperature, is condensed into ball, collects drop pill, removes coolant, drying, promptly.
6. according to the described drop pills of amlodipine of claim 1～5, it is characterized in that said medicinal adjuvant comprises drop pill substrate, surfactant (contain or do not contain), cosolvent (contain or do not contain).
7. according to the medicinal adjuvant in the drop pills of amlodipine of the described preparation of claim 1～6, it is characterized in that:
(1) described substrate is meant that molecular weight is equal to or greater than one or more the compositions in 1500 Polyethylene Glycol, Myrj 45, sodium stearate, glycerin gelatine, stearic acid, glyceryl monostearate, hydrogenated vegetable oil, the insect wax.The compositions of preferred Polyethylene Glycol-4000, Polyethylene Glycol-6000 and different proportion thereof.
(2) described surfactant comprises but is not limited to poloxamer, dodecyl sodium sulfate, CMS-Na, tween 80.Preferred tween 80 and CMS-Na.
(3) described cosolvent includes but not limited to ethanol, propylene glycol, glycerol, liquid macrogol.Preferred alcohol.
(4) described condensed fluid is selected from liquid paraffin, methyl-silicone oil, vegetable oil, kerosene etc.Preferred liquid paraffin, methyl-silicone oil.
8. according to the technical parameter of the described drop pills of amlodipine preparation method of claim 5, it is characterized in that:
(1) holding temperature of fused solution is 60 ℃～110 ℃, temperature retention time at least 20 minutes; In the time of preferred 70～95 ℃, temperature retention time at least 30 minutes.
(2) temperature on condensed fluid top is 10～45 ℃, and the temperature of condensed fluid bottom is-10～10 ℃.The temperature on preferred top is 20～30 ℃, and the temperature of condensed fluid bottom is-5～5 ℃.
(3) dripping fast scope is 10～100/min, and keeping dripping distance is 2～8cm.Preferred 30～70/min, dripping distance is 2～5cm.
According to the bioavailability of the prepared drop pills of amlodipine of claim 1～7 30～95%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610080743 CN1915225A (en) | 2005-06-07 | 2006-05-16 | Drop pills of Amlodipine, and preparation method |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200510074843.7 | 2005-06-07 | ||
| CN200510074843 | 2005-06-07 | ||
| CN 200610080743 CN1915225A (en) | 2005-06-07 | 2006-05-16 | Drop pills of Amlodipine, and preparation method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1915225A true CN1915225A (en) | 2007-02-21 |
Family
ID=37736385
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200610080743 Pending CN1915225A (en) | 2005-06-07 | 2006-05-16 | Drop pills of Amlodipine, and preparation method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1915225A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109432033A (en) * | 2018-12-26 | 2019-03-08 | 成都恒瑞制药有限公司 | Amlodipine besylate dropping pills and preparation method thereof |
-
2006
- 2006-05-16 CN CN 200610080743 patent/CN1915225A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109432033A (en) * | 2018-12-26 | 2019-03-08 | 成都恒瑞制药有限公司 | Amlodipine besylate dropping pills and preparation method thereof |
| CN109432033B (en) * | 2018-12-26 | 2021-03-30 | 成都恒瑞制药有限公司 | Amlodipine besylate dripping pill and its prepn |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1915225A (en) | Drop pills of Amlodipine, and preparation method | |
| CN1899268A (en) | L-amlodipine besilate dripping pill and its preparing method | |
| CN1265785C (en) | Chrono-slow-releasing prepn. hydrochloride verapamil | |
| CN1875972A (en) | Preparation of ligustrazine and ligustrazine salt drop pills utilizing nano technology | |
| CN1272001C (en) | Aniracetam drop pills | |
| CN1875980A (en) | Drop pills of vepeside and preparation process thereof | |
| CN1686123A (en) | Pyrolidone hydrochloride drip pill and its preparation method | |
| CN1939282A (en) | Amlodipine benesanli dropping balls and production thereof | |
| CN1309379C (en) | Asari dripping pills and its preparation process | |
| CN1559388A (en) | Tramadol hydrochloride oral disintegration tablets, and prepn. method therefor | |
| CN1686362A (en) | Hairy holly root drip pill and its preparation method | |
| CN1526379A (en) | Sibutramine hydrochloride dripping pill and its prepn | |
| CN1634080A (en) | Spironolactone dripping pills | |
| CN1879621A (en) | Drop pills of amlodipine maleate and preparation method thereof | |
| CN1301094C (en) | Throat pain relieving anti-inflammation drop pills for treating oral disease and preparation method thereof | |
| CN1586481A (en) | Procaterol dripping pill and its preparing method | |
| CN1634490A (en) | Drop pills for treating throat diseases and preparation method thereof | |
| CN1634472A (en) | Drop pills containing bear gall and tendril-leaved fritillary bulb and preparation method thereof | |
| CN1698797A (en) | Blood pressure lowering dripping pills with chryanthemum flower and pearl and its preparation process | |
| CN1989997A (en) | Drop pill for treating pharyngitis and its preparation method | |
| CN1679675A (en) | Chuanhuang anti-inflammation drops for clearing away heat and detoxicating, and preparation thereof | |
| CN1686125A (en) | Rogelinone drip pill and its preparation method | |
| CN1526393A (en) | Hydralazine hydrochloride guttate pills and the prepn | |
| CN1679669A (en) | Polygala dropping balls and preparation thereof | |
| CN1528295A (en) | Indapamide drop pill and preparing method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |