CN103908443A - Propafenone hydrochloride sustained-release capsule and preparation method thereof - Google Patents
Propafenone hydrochloride sustained-release capsule and preparation method thereof Download PDFInfo
- Publication number
- CN103908443A CN103908443A CN201310603371.4A CN201310603371A CN103908443A CN 103908443 A CN103908443 A CN 103908443A CN 201310603371 A CN201310603371 A CN 201310603371A CN 103908443 A CN103908443 A CN 103908443A
- Authority
- CN
- China
- Prior art keywords
- propafenone hydrochloride
- slow releasing
- releasing capsule
- release
- propafenone
- 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
Abstract
The invention relates to a propafenone hydrochloride sustained-release capsule and a preparation method thereof. The propafenone hydrochloride sustained-release capsule is prepared by filling sustained-release micro-tablets with the diameter of 2-3 mm, and has good dosage dispersion and uniformity. The micro tablets are composed of propafenone hydrochloride, a framework material, a lubricant and a diluent. The framework material is one or more of methyl cellulose, ethyl cellulose, hydroxypropyl methylcellulose and povidone; and a usage amount of the framework material is 1%-10%. The lubricant is one or more of sodium stearyl fumarate, magnesium stearate, micro-powder silica gel, talcum powder, calcium stearate and polyethylene glycol; and a usage amount of the lubricant is 0.1%-1.5%. The diluent is one or more of sucrose, mannitol, microcrystalline cellulose, lactose and polyethylene glycol; and a usage amount of the diluent is 2%-12%. According to the propafenone hydrochloride sustained-release capsule, the usage amount of a main drug is 77%-98%; and propafenone level in blood plasma reaches the maximum value 3-8 hours after drug delivery. The propafenone hydrochloride sustained-release capsule is stable in drug release and has a good sustained-release effect. An object of the invention is to provide a preparation method of the propafenone hydrochloride sustained-release capsule. The preparation method is simple in process, high in yield, good in stability and suitable for large-scale production.
Description
Technical field
The present invention relates to a kind of propafenone hydrochloride preparation, particularly slow releasing preparation and preparation method thereof.
Background technology
Propafenone hydrochloride (C
21h
27nO
3hCl) be the Ic class anti-arrhythmic with local anesthesia effect, Main Function is the sodium-ion channel of blocking-up myocardial cell.Be used for the treatment of clinically chamber property, Dou Xing, supraventricular tachycardia and preexcitation syndrome etc.1975 synthetic first by German Hxlppharm company, and nineteen eighty-two, China copied successfully.Conventional oral ordinary preparation, within 0.5～1 hour after taking, start effect, within 2～3 hours, reach peak plasma concentration, effect continues 4～8 hours, therefore take ordinary tablet therapeutic dose day 3～6 times, bring like this inconvenience, and untoward reaction is while having more the peak after present administration, has therefore thereupon occurred the research of the slow controlling agent of propafenone hydrochloride, slow releasing preparation can reduce the blood drug level peak valley phenomenon of ordinary tablet, reduce the untoward reaction of medicine, and reduce administration number of times, facilitate patient to use.
In the prior art, propafenone hydrochloride slow releasing preparation relates generally to two classes: the propafenone hydrochloride slow releasing preparation that the slow release methods such as propafenone hydrochloride slow release microplate and skeleton are prepared from.
Microplate refers to through special tablet machine stamping suppresses the diameter that the forms micro tablet between 1～3mm.Microplate is similar to micropill on clinical effectiveness, belongs to dosage decentralized preparation.After the oral microplate of patient, dispersed in gastrointestinal tract, the gastrointestinal transit of medicine and absorption are subject to the impact of gastric emptying rate less, thereby the drug release behavior of the little microplate of individual difference is the summation of multiple junior unit drug release behaviors of a dosage of composition, defect in oral rear indivedual junior unit preparation technologies can not produce serious influence to the drug release behavior of overall preparation, can utilize the slow release method such as coating or skeleton, the junior unit of several different release rules is combined into multiple unit system, to obtain desirable rate of releasing drug, obtain desirable therapeutic effect.The more important thing is, because the medicine of a dosage is dispersed in multiple separate small unit, oral contact area rear and gastrointestinal tract thin film increases, thereby can improve the bioavailability of medicine, also can reduce or eliminate some drugs to gastrointestinal zest.According to clinical needs, can will after microplate coating, incapsulate, pro ore, also can not coatedly directly incapsulate pro ore.
2003, propafenone hydrochloride slow releasing capsule (the 12 hours slow release) listing of Abbott of U.S. development and production, the micro chip that is a kind of 2 × 2mm incapsulates, in-built approximately 50～60 micro chips of every capsules, its technical scheme is open in PCT patent Chinese literature CN1120312A, be characterized in propafenone hydrochloride and auxiliary substance thereof to be prepared into micro tablet, this tablet does not contain slow release auxiliary substance, control the slow release of active component Propafenone with the slow controlled release feature of microplate, its complicated process of preparation, supplementary product kind is many, be unfavorable for absorption of human body metabolism, clinical drug safety has much room for improvement.
The domestic research about propafenone hydrochloride slow releasing preparation in recent years occurs successively.
Chinese patent literature CN102805738A discloses a kind of propafenone hydrochloride slow releasing preparation that utilizes hydrophilic gel slow release method to prepare, this propafenone hydrochloride slow releasing preparation contains main constituent and hydrophilic gel blocker, if one or more the percentage by weight in polymer starch, methylcellulose, sodium carboxymethyl cellulose, hydroxypropyl emthylcellulose, PEG is 2: 1～5: 1, contain 3%～10% filler and suitable lubricant simultaneously.The propafenone hydrochloride slow releasing preparation of preparation maintained stable blood drug level in 12 hours, and had release profiles in the body similar to the propafenone hydrochloride slow releasing capsule of Abbott of U.S. development and production, and said preparation is suitable for twice administration in oral a day.
" central composite design method is optimized propafenone hydrochloride slow-release micro-pill coating fluid prescription " that be published in " China Medicine University's journal " discloses and a kind of day taken the propafenone hydrochloride slow-release micro-pill of 2 times, utilize this medium permeable material of Eudragit NE30D to make slow releasing preparation, its preparation method be by propafenone hydrochloride and microcrystalline Cellulose in mass ratio the ratio of 1:1 sieve and mix, add suitable quantity of water to make wet feed, be extruded into the strip of equal diameters through sieve plate, put the interior round as a ball plain ball of making of spheronizator, adopt afterwards Eudragit NE30D to carry out coating and make micropill.
" preparation of propafenone hydrochloride matrix type slow-release micro-pill and the discussion of release Mechanisms thereof " that be published in " Chinese journal of Practical Pharmacy " discloses the propafenone hydrochloride matrix type slow-release micro-pill of preparing by extrude～spheronization after a kind of bulk density that adopts fusion method to improve cured material, and its drug release process is mainly corrosion process.
" preparation and the quality evaluation of the slow double-deck micropill of propafenone hydrochloride speed " that be published in equally " Chinese journal of Practical Pharmacy " discloses the slow double-deck micropill of a kind of propafenone hydrochloride speed, the slow double-deck micropill of this propafenone hydrochloride speed is to adopt Film coating to prepare slow release kernel, with adopt liquid phase lamination and two kinds of methods of powder lamination to prepare the rapid release skin of double-deck micropill, thereby reach after administration the object of the slow merger of speed that onset rapidly simultaneously can long period onset.
Domestic these utilize propafenone hydrochloride slow releasing preparation that the slow release methods such as coating/skeleton are prepared to obtain to a certain extent the effect of slow release above, but existent defect: (1) tablet volume ratio is larger, and bioavailability is low, not welcome by patient simultaneously; (2) medicine homogeneity is poor, very high to coating effect requirement, once there is slight peplos breakage to cause the sudden outburst of whole active component contents, thus have side effects; (3) biologicak efficiency of slow-release micro-pill is subject to feeding impact greatly, large with intraindividual diversity between individuality.
Summary of the invention
The object of this invention is to provide a kind of propafenone hydrochloride slow releasing capsule, release is slowly steady, " peak valley " phenomenon of having avoided conventional capsule or tablet to produce.Its release in vitro behavior meets Higuchi equation, shows the feature of zero-order release.Medicining times is also reduced to for 3～4 times 1 time by every day, has improved the compliance that patient takes medicine.
The present invention is by medicine and suitable framework material, and adjuvant mixes, and is pressed into micro chip, and incapsulates after granulating.
The invention provides a kind of is the propafenone hydrochloride slow releasing capsule that the filling of 1～3mm slow release microplate forms by diameter.Said preparation technique is simple, and yield is high, and good stability is applicable to industrialized mass.
The present invention relates to a kind of propafenone hydrochloride slow releasing capsule, it is characterized in that described slow releasing capsule is made up of active ingredient propafenone hydrochloride, framework material, lubricant, filler, capsule shells.Wherein said framework material is selected from that starch, carboxymethylstarch are received, one or more in ethyl cellulose, methylcellulose, hypromellose, polyvidone, polyacrylic resin base polymer, preferably polyvidone, hypromellose, ethyl cellulose, more preferably ethyl cellulose; Lubricant is selected from one or more of magnesium stearate, Pulvis Talci, micropowder silica gel, calcium stearate, hard fumaric acid sodium, Polyethylene Glycol apoplexy due to endogenous wind, preferably micropowder silica gel, magnesium stearate, Pulvis Talci, more preferably Pulvis Talci.Filler is selected from one or more in lactose, sucrose, mannitol, microcrystalline Cellulose, Polyethylene Glycol, ethanol, preferably lactose.
The present invention relates to a kind of propafenone hydrochloride preparation method, its preparation technology is:
(1) material is prepared: by propafenone hydrochloride, and framework material, filler, lubricant sieves for subsequent use.
(2) granulate: take framework material and the filler of recipe quantity, mix homogeneously.Propafenone hydrochloride and mixed accessories are mixed, granulate, be drying to obtain.
(3) compacting microplate: granule and lubricant are mixed, put in tablet machine and suppress.
(4) incapsulate, pack and get final product.
The present invention has investigated that ethyl cellulose, carboxymethylstarch are received, one or more framework materials and the impact of consumption on drug release thereof in methylcellulose, hypromellose, polyvidone, experimental result shows, in the time that framework material consumption is less than 10%, be difficult to form continuous hydrophilic gel layer, main manifestations is dilatancy drug release.
Suitable framework material in this drug component is a kind of cellulose family, and in one embodiment, this framework material is ethyl cellulose, in another embodiment, this framework material is hypromellose, and its amount ranges is recipe quantity 1%～10%, preferably 2%～8%.Propafenone hydrochloride slow releasing capsule and the conventional capsule of preparation are contrasted, experimental result shows: propafenone hydrochloride slow releasing capsule 2h release 10～30%, 4h release 20～50%, 10h release is more than 75%, and propafenone hydrochloride ordinary tablet is in 45min stripping more than 70%, thereby propafenone hydrochloride slow releasing capsule has significant slow release effect.
The present invention has investigated the impact of variable grain particle diameter on compacting microplate, the granule that particle diameter is 0.8～4.0mm, and its good fluidity, but because particle diameter is excessive, tabletting filling is subject to unstable, loading amount is inhomogeneous, easily damages special-shaped plunger chip simultaneously.Particle diameter is the granule of 0.2～0.8mm, its good fluidity, and compressibility is strong, uniform filling.
The present invention has investigated different baking temperatures, and the impact of drying time on compacting microplate used 50～65 DEG C to be dried 8 hours, its good fluidity, and compressibility is strong, is applicable to the compacting of propafenone hydrochloride microplate.
The present invention is to pressing exponential sum Hausner ratio to measure, can end finger number=(tapped density-bulk density) × 100/ tapped density, and Hausner ratio=tapped density/bulk density, experimental result shows end finger number to be 8%, in 6%～12% scope, Hausner ratio is 1.05, and compressibility is good.
A kind of propafenone hydrochloride microplate of the present invention's compacting, its microplate diameter is 1～3mm, height is 1～5mm, is column.This microplate good looking appearance, smooth bright, homogeneity is good.
A kind of propafenone hydrochloride microplate of the present invention's compacting, incapsulates, and after patient is oral, medicine is uniformly dispersed at gastrointestinal tract, is subject to the impact of gastric emptying rate less, so that the individual variation producing is relatively little.Can not affect drug release behavior, make medicine Stable Release, reach optimal treatment effect simultaneously.
A kind of propafenone hydrochloride slow releasing capsule prepared by the present invention has overcome the shortcoming of ordinary preparation, has improved patient's compliance, makes lasting medicine, stable curative effect.
Below in conjunction with embodiment, the invention will be further described.
Brief description of the drawings:
Fig. 1 propafenone hydrochloride slow releasing capsule (embodiment 1) release curve
Fig. 2 propafenone hydrochloride slow releasing capsule (embodiment 2) release curve
Fig. 3 propafenone hydrochloride slow releasing capsule (embodiment 3) release curve
Fig. 4 propafenone hydrochloride slow releasing capsule (embodiment 4) release curve
Fig. 5 propafenone hydrochloride slow releasing capsule (embodiment 5) release curve
Fig. 6 propafenone hydrochloride slow releasing capsule (embodiment 6) and Rythmol
release curve
Fig. 7 propafenone hydrochloride slow releasing capsule (embodiment 7) stability release curve
Detailed description of the invention
In the present invention, described propafenone hydrochloride slow releasing capsule preparation method is, by propafenone hydrochloride, with the framework material of recipe quantity, filler mix homogeneously, to drying baker, to be dried.The taking-up granulate that sieves, mixes the lubricant of the granule making and recipe quantity, and compacting microplate, incapsulates and get final product.
In the present invention, described propafenone hydrochloride slow releasing capsule drug release determination method, taking hydrochloric acid and buffer as medium, adopts certain rotating speed, is under 37.0 DEG C of conditions in temperature, discharges 1 hour through hydrochloric acid medium, 2 hours, gets filtrate detection.Acid phase adds the phosphate buffer of 37 DEG C after 2 hours, through 2 hours, 4 hours, 8 hours, 10 hours, within 13 hours hours, get filtrate detection, according to detecting containing the detection method under quantifier.
Below in conjunction with embodiment, embodiment of the present invention are described in detail, described embodiment is only for the present invention is described, and should not be considered as limiting scope of the present invention.In embodiment, unreceipted actual conditions person, carries out according to normal condition.The unreceipted person of production firm of agents useful for same or instrument, being can be by the conventional products of commercial acquisition.
Embodiment 1
Embodiment 2
Embodiment 3
Embodiment 4
Embodiment 5
Embodiment 6
The present invention is by (embodiment 1) propafenone hydrochloride slow releasing capsule and the Rythmol of GlaxoSmithKline PLC company
carry out dissolution test simultaneously, in 37.0 DEG C, under per minute 50 conditions that turn, compare both at 1 hour, 2 hours, 4 hours, 8 hours, 10 hours, 12 hours, the release of 15 hours.
Table 1 propafenone hydrochloride slow releasing capsule and Rythmol
release research
Embodiment 7 propafenone hydrochloride slow releasing capsule study on the stability
In order further to evaluate the stability of the propafenone hydrochloride slow releasing capsule described in the present invention, with reference to Chinese Pharmacopoeia two annex XIX C crude drug of version in 2012 and pharmaceutical preparation stability test guideline, under the condition of 40 DEG C ± 2 DEG C of temperature, relative humidity 75% ± 5, place 6 months, the 1st, 2,3,6 the end of month respectively to propafenone hydrochloride slow releasing capsule (prepared by above-described embodiment 1) and the Rythmol of GlaxoSmithKline PLC company
carry out character, content, related substance and release detect.
Character checks
With visual method, sample is checked to (the results are shown in Table 2), result shows that propafenone hydrochloride slow releasing capsule character during stability assessment prepared by the present invention does not change.
The detection of content and related substance
In the present invention, described propafenone hydrochloride slow releasing capsule content and the detection method of related substance are that mobile phase is acetonitrile taking octyl silicon bonded silica gel as filler, methanol, phosphate buffer, flow velocity 1.0ml/min, detect wavelength 248nm, detect (the results are shown in Table 2).Result shows that its content of propafenone hydrochloride slow releasing capsule prepared by the present invention and the stability of related substance meet the regulation in ICH Q3B.
Release detects
This routine sample is carried out to dissolution detection, the results are shown in Figure 7, result shows that its release of propafenone hydrochloride slow releasing capsule prepared by the present invention has good stability.
Table 2 propafenone hydrochloride slow releasing capsule and Rythmol
stability study
Claims (11)
1. a propafenone hydrochloride slow releasing capsule; it is characterized in that the slow release microplate filling that described slow releasing capsule is 1～3mm by diameter forms; every capsules fills 35～85 slow release microplates, and this microplate comprises active ingredient propafenone hydrochloride, framework material, lubricant, filler.
2. the microplate of a kind of propafenone hydrochloride slow releasing capsule according to claim 1, is characterized in that: the cylindrical or cylindrical shape of this microplate, and its diameter is 1～3mm, height is 1～5mm.
3. a kind of propafenone hydrochloride slow releasing capsule according to claim 1 and 2, is characterized in that: described microplate component ratio is as follows: the consumption (weight ratio) of propafenone hydrochloride is 77～98; The consumption of framework material is 1～10; The consumption of lubricant is 0.1～1.5; The consumption of filler is 2～12.
4. according to a kind of propafenone hydrochloride slow releasing capsule described in claim 1 or 3, it is characterized in that described framework material is selected from one or more in carboxymethylstach sodium, ethyl cellulose, methylcellulose, hypromellose, polyvidone, polyacrylic resin base polymer.
5. a kind of propafenone hydrochloride slow releasing capsule according to claim 4, is characterized in that described framework material is ethyl cellulose.
6. according to a kind of propafenone hydrochloride slow releasing capsule described in claim 1 or 3, it is characterized in that described lubricant is selected from one or more of magnesium stearate, Pulvis Talci, micropowder silica gel, calcium stearate, hard fumaric acid sodium, Polyethylene Glycol apoplexy due to endogenous wind.
7. a kind of propafenone hydrochloride slow releasing capsule according to claim 6, is characterized in that described lubricant is Pulvis Talci.
8. according to a kind of propafenone hydrochloride slow releasing capsule described in claim 1 or 3, it is characterized in that described filler is selected from one or more in lactose, sucrose, mannitol, microcrystalline Cellulose, dextrin, starch.
9. a kind of propafenone hydrochloride slow releasing capsule according to claim 8, is characterized in that described filler is lactose.
10. according to a kind of propafenone hydrochloride slow releasing capsule described in claim 1 or 3, it is characterized in that the drug particles compacting that described microplate is 0.2～0.8mm by particle diameter forms, its good fluidity, compressibility is strong, uniform filling.
11. according to the preparation method of a kind of propafenone hydrochloride slow releasing capsule described in claim 1 or 3, and its preparation technology is: propafenone hydrochloride, framework material, lubricant, filler are sieved, and mix homogeneously is dried to drying baker.The taking-up granulate that sieves, by the granule compacting microplate making, incapsulates and get final product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310603371.4A CN103908443A (en) | 2013-11-25 | 2013-11-25 | Propafenone hydrochloride sustained-release capsule and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310603371.4A CN103908443A (en) | 2013-11-25 | 2013-11-25 | Propafenone hydrochloride sustained-release capsule and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103908443A true CN103908443A (en) | 2014-07-09 |
Family
ID=51034650
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310603371.4A Pending CN103908443A (en) | 2013-11-25 | 2013-11-25 | Propafenone hydrochloride sustained-release capsule and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103908443A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105902984A (en) * | 2016-05-29 | 2016-08-31 | 山东仁和堂药业有限公司 | Propafenone hydrochloride tablets and preparation method thereof |
| CN106420669A (en) * | 2016-10-25 | 2017-02-22 | 赛乐医药科技(上海)有限公司 | Propafenone hydrochloride sustained-release micro-tablet capsule and preparation method and application thereof |
| CN107441051A (en) * | 2016-05-30 | 2017-12-08 | 北京科信必成医药科技发展有限公司 | A kind of propafenone hydrochloride microplate and preparation method thereof |
| CN108014097A (en) * | 2017-12-20 | 2018-05-11 | 北京双鹭药业股份有限公司 | A kind of temozolomide sustained-release capsule and preparation method thereof |
| CN112315942A (en) * | 2020-11-04 | 2021-02-05 | 南京康川济医药科技有限公司 | Trimetazidine hydrochloride sustained release preparation and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5681588A (en) * | 1993-04-03 | 1997-10-28 | Knoll Aktiengesellschaft | Delayed release microtablet of β-phenylpropiophenone derivatives |
-
2013
- 2013-11-25 CN CN201310603371.4A patent/CN103908443A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5681588A (en) * | 1993-04-03 | 1997-10-28 | Knoll Aktiengesellschaft | Delayed release microtablet of β-phenylpropiophenone derivatives |
Non-Patent Citations (2)
| Title |
|---|
| PAWAR SUSHIL J. ETAL: "Design and Evaluation of an Extended Release Drug Delivery System of Propafenone Hydrochloride", 《RESEARCH JOURNAL OF PHARMACY AND TECHNOLOGY》 * |
| PRAVEEN KUMAR MANTHENA ETAL: "FORMULATION AND EVALUATION OF PROPAFENONE HYDROCHLORIDE EXTENDED RELEASE TABLETS", 《PHARMACIE GLOBALE》 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105902984A (en) * | 2016-05-29 | 2016-08-31 | 山东仁和堂药业有限公司 | Propafenone hydrochloride tablets and preparation method thereof |
| CN107441051A (en) * | 2016-05-30 | 2017-12-08 | 北京科信必成医药科技发展有限公司 | A kind of propafenone hydrochloride microplate and preparation method thereof |
| CN107441051B (en) * | 2016-05-30 | 2022-09-16 | 北京科信必成医药科技发展有限公司 | Propafenone hydrochloride micro-tablet and preparation method thereof |
| CN106420669A (en) * | 2016-10-25 | 2017-02-22 | 赛乐医药科技(上海)有限公司 | Propafenone hydrochloride sustained-release micro-tablet capsule and preparation method and application thereof |
| CN108014097A (en) * | 2017-12-20 | 2018-05-11 | 北京双鹭药业股份有限公司 | A kind of temozolomide sustained-release capsule and preparation method thereof |
| CN108014097B (en) * | 2017-12-20 | 2021-01-05 | 北京双鹭药业股份有限公司 | Temozolomide sustained-release capsule and preparation method thereof |
| CN112315942A (en) * | 2020-11-04 | 2021-02-05 | 南京康川济医药科技有限公司 | Trimetazidine hydrochloride sustained release preparation and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR100762847B1 (en) | Multiple unit type sustained release oral formulation and process for the preparation thereof | |
| WO2011063732A1 (en) | Paliperidone double-layered osmotic pump controlled release tablet and preparation method thereof | |
| CN101987091B (en) | Venlafaxine hydrochloride sustained-release pellet capsules | |
| CN101574323B (en) | Migltol microcapsule tablet and preparation method thereof | |
| WO2000009133A1 (en) | Sustained release oral preparations of fasudil hydrochloride | |
| CN103908443A (en) | Propafenone hydrochloride sustained-release capsule and preparation method thereof | |
| CN101933907A (en) | Novel matrix sustained-release tablet and preparation method thereof | |
| CN104173312A (en) | Sustained-release tablet containing felodipine and metoprolol salt and preparation method of sustained-release tablet containing felodipine and metoprolol salt | |
| CN114146062B (en) | Composition and preparation method and application thereof | |
| CN102091069A (en) | Valsartan and amlodipine compound preparation and preparation method thereof | |
| CN103251593B (en) | Repaglinide/metformin composition | |
| CN102772395A (en) | Sustained release preparation containing ambroxol hydrochloride and clenbuterol hydrochloride, and preparation method thereof | |
| CN109646417B (en) | Trimetazidine sustained release tablet and preparation method thereof | |
| CN106031715B (en) | A kind of Doxycycline Hyclate sustained release preparation and preparation method thereof | |
| CN101099762B (en) | Blood pressue lowering sustained-release preparation with chrysanthemum flower and pearl | |
| CN102772392B (en) | Arbidol sustained or controlled release capsule and preparation method thereof | |
| CN102058564A (en) | Zaltoprofen slow-release/controlled-release preparation and preparation method thereof | |
| JP2012503020A (en) | Organic galenic formulation | |
| CN109394722A (en) | Propafenone microplate, multiple-unit formulation comprising the microplate and its preparation method and application | |
| CN102188388B (en) | Diclofenac sodium sustained-release pellet preparation and preparation method thereof | |
| CN105687157A (en) | Levofloxacin hydrochloride capsule and preparation method thereof | |
| CA2897302C (en) | Sustained release formulations of lorazepam | |
| CN103550182B (en) | Enteric-coated sustained release composition | |
| CN107441051B (en) | Propafenone hydrochloride micro-tablet and preparation method thereof | |
| CN105168183A (en) | Gliclazide sustained-release capsule and preparation method and application 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 | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20140709 |
|
| WD01 | Invention patent application deemed withdrawn after publication |