CN109646391A - Tolvaptan sustained release preparation and preparation method thereof - Google Patents
Tolvaptan sustained release preparation and preparation method thereof Download PDFInfo
- Publication number
- CN109646391A CN109646391A CN201811566088.8A CN201811566088A CN109646391A CN 109646391 A CN109646391 A CN 109646391A CN 201811566088 A CN201811566088 A CN 201811566088A CN 109646391 A CN109646391 A CN 109646391A
- Authority
- CN
- China
- Prior art keywords
- tolvaptan
- sustained release
- release preparation
- preparation
- hydroxypropyl methylcellulose
- 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
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/02—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
Abstract
The invention discloses a kind of tolvaptan sustained release preparations and preparation method thereof, the tolvaptan sustained release preparation is made of tolvaptan, hydroxypropyl methylcellulose and excipient, the dosage of the hydroxypropyl methylcellulose is the 30%~45% of tolvaptan sustained release preparation total amount, the range of viscosities of the hydroxypropyl methylcellulose is 50mPa s to 10000mPa s, and the excipient includes one of diluent, disintegrating agent, lubricant or two or more.Tolvaptan sustained release preparation of the invention can be prepared using technique of direct powder compression, can also be using conventional pelletizing press sheet technique preparation.Tolvaptan sustained release preparation of the invention can improve the release in vitro of drug, reduce the peak valley phenomenon of blood concentration, to improve Drug safety, validity and adaptability, and stability is not affected, simple production process, favorable reproducibility, and industrialization degree is high, and conventional production equipment can be used and amplify production.
Description
Technical field
The invention belongs to pharmaceutical preparations technology fields, and in particular to a kind of tolvaptan sustained release preparation and preparation method thereof.
Background technique
Tolvaptan is developed by Japanese great Zhong drugmaker (Otsuka Pharmaceutical Co.), 2009
Year lists in US and European respectively, lists in Japan within 2010, trade name: Samsca [Chinese is Su Maika].Support is cut down
Pu Tan is specific antagonist arginine vasopressin, for treating the capacitives hyponatremia companion heart failure such as high perhaps, cirrhosis, resisting
Diuretic hormone diacrisis syndrome.Its chemical name is: N- [4- [the chloro- 5- hydroxyl -2,3,4,5- tetrahydro -1- benzene of (5R) -7-
And azatropylidene -1- formoxyl] -3- aminomethyl phenyl] -2- methyl benzamide, structural formula is as follows:
。
Tolvaptan is a kind of vasopressing V2 receptor antagonist (non-peptides AVP2 receptor antagonist), can increase blood
Na ion concentration in slurry helps extra moisture to be discharged from urine, the ability of enhancing kidney processing water.Currently, commercial product is revived
Mai Kawei quick releasing formulation, for blood concentration 2h i.e. up to peak, half-life period is 3~4h, is absorbed comparatively fast, this results in tolvaptan piece
Too fast correction Serum Na+ concentration may cause serious nervous system sequelae, while dehydration and hypovolemia, and there are potential
Hepatic lesion risk.
In April, 2012, British Drug and health-oriented products management board (MHRA) give a warning: it is fast that tolvaptan can lead to blood sodium
Speed increases and causes serious neurological symptoms, can cause permeability demyelinate symptom, lead to dysphonia, hoarseness, swallow it is tired
Difficulty, lethargic sleep, emotion variation, spastic quadriplegia, twitch, stupor are even dead.
On April 30th, 2012, it is serious and possible fatal that Food and Drug Adminstration of the US (FDA) announces that tolvaptan exists
Risk of liver injury, the risk of this kind of death or severe liver injury increases, it may be necessary to liver transfer operation, thus need to cut down to support general
New limitation is arranged in smooth use.
In order to avoid this product discharges rapidly in vivo, there is peak valley phenomenon in blood concentration in clinical use, causes blood medicine dense
It is quickly eliminated after the of short duration raising of degree, clinically needs tolvaptan sustained release preparation.
The related report of tolvaptan sustained release preparation is not yet found at present.
Summary of the invention
The purpose of the present invention is to solve the above problem, provides release in vitro, reduction blood medicine that one kind can improve drug
Impregnable tolvaptan sustained release preparation of the peak valley phenomenon and stability of concentration and preparation method thereof.
Realizing the technical solution of the object of the invention is: a kind of tolvaptan sustained release preparation, it is by tolvaptan, hydroxypropyl first
Cellulose and excipient are made.
The dosage of the tolvaptan is 5mg~30mg.
In order to prepare good sustained release preparation, the dosage of the hydroxypropyl methylcellulose is at least tolvaptan sustained release preparation
The 30% of total amount, preferably 30%~45%.
In order to prepare more good sustained release preparation, the range of viscosities of the hydroxypropyl methylcellulose be 3mPa s~
100000mPa s, preferably 50mPa s to 10000mPa s.
The hydroxypropyl methylcellulose of above-mentioned range of viscosities can be prepared by well known method, can also use commercial product；
Commercial goods include but is not limited to METHOCEL series and SH serial (the Anhui mountains and rivers)；The METHOCEL series include but
It is not limited to E50LV, K100LV, K100LV CR, K4M, K4M CR, E4M, E4M CR, E10M, E10M CR etc.；The SH series
Including but not limited to E50, E100, K4M, K10M etc..
The hydroxypropyl methylcellulose can use a kind of hydroxypropyl methylcellulose of viscosity, (can also be contained using two or more
Two kinds) hydroxypropyl methylcellulose of viscosity.
The excipient includes one of diluent, disintegrating agent, lubricant or two or more (containing two kinds).
The diluent is selected from one of lactose, microcrystalline cellulose, cornstarch or two or more (containing two kinds).
The dosage of the diluent is the 40~60% of tolvaptan sustained release preparation total amount.
The disintegrating agent in low-substituted hydroxypropyl cellulose, crospovidone, croscarmellose sodium one
Kind is two or more (containing two kinds).
The dosage of the disintegrating agent is the 1%~10% of tolvaptan sustained release preparation total amount, preferably 3~7%.
The lubricant be selected from one of magnesium stearate, talcum powder, colloidal silicon dioxide or it is two or more (contain two
Kind).
The dosage of the lubricant is the 0.1%~10%, preferably 0.5~5% of tolvaptan sustained release preparation total amount, more excellent
It is selected as 1%.
The dosage form of tolvaptan sustained release preparation of the invention is tablet.
Tolvaptan sustained release preparation of the invention can be prepared using technique of direct powder compression, can also be using routine
Pelletizing press sheet technique preparation, it is preferred to use technique of direct powder compression preparation.
The specific method is as follows for the technique of direct powder compression: first carrying out tolvaptan raw material and hydroxypropyl methylcellulose pre-
Mixing；Then the excipient in addition to lubricant is added and continuess to mix, be added followed by lubricant and continues to mix, finally will
Mixed powder directly carries out tabletting, obtains sustained release preparation.
The conventional pelletizing press sheet technique is preferably high shear pelletizing press sheet technique, and the specific method is as follows: first will be except profit
Appropriate purified water granulation is added in component other than lubrication prescription after mixing, is then dried, whole grain, is added followed by lubricant
It is mixed, finally discharging and tabletting.
Above two method can also be coated after carrying out tabletting.
The good effect that the present invention has: tolvaptan sustained release preparation of the invention can improve the release in vitro of drug,
The peak valley phenomenon for reducing blood concentration, to improve Drug safety, validity and adaptability, and stability is not by any
It influences, simple production process, favorable reproducibility, and industrialization degree is high, and conventional production equipment can be used and amplify life
It produces.
Detailed description of the invention
Fig. 1 is that tolvaptan sustained release preparation made from embodiment 1 and commercial goods Soviet Union wheat are stuck in Beagle dog body
Pharmacokinetic studies result figure.
Specific embodiment
(embodiment 1)
The tolvaptan sustained release preparation formula of the present embodiment is shown in Table 1.
Table 1
| Ingredient | Single dose mg/ piece | Specifications and models | Weight percent |
| Tolvaptan | 15 | / | 7.5% |
| Hydroxypropyl methylcellulose (100mPas) | 40 | METHOCEL™ K100LV | 20% |
| Hydroxypropyl methylcellulose (4000mPas) | 20 | METHOCEL™ K4M CR | 10% |
| Lactose | 56 | 200 mesh | 28% |
| Microcrystalline cellulose | 57 | PH 102 | 28.5% |
| Low-substituted hydroxypropyl cellulose | 10 | LH-21 | 5% |
| Magnesium stearate | 2 | / | 1% |
| Gross weight | 200 | / | / |
The preparation method of the tolvaptan sustained release preparation of the present embodiment is direct powder compression, specific as follows:
1. first tolvaptan and hydroxypropyl methylcellulose (100mPas and 4000mPas) are placed in three-dimensional mixed according to recipe quantity
15min is mixed in conjunction machine.
2. lactose, microcrystalline cellulose and low-substituted hydroxypropyl cellulose is then added, 20min is continuesd to mix.
3. being subsequently added into magnesium stearate, 5min is continuesd to mix.
4. 3. powder that step is mixed to get directly carries out tabletting, every piece weighs about 200mg(totally 10000), finally
It is coated.
(embodiment 2)
The tolvaptan sustained release preparation formula of the present embodiment is shown in Table 2.
Table 2
| Ingredient | Single dose mg/ piece | Specifications and models | Weight percent |
| Tolvaptan | 15 | / | 7.5% |
| Hydroxypropyl methylcellulose (50mPas) | 90 | METHOCEL™ E50LV | 45% |
| Cornstarch | 30 | 200 mesh | 15% |
| Microcrystalline cellulose | 57 | PH 101 | 28.5% |
| Crospovidone | 6 | XL | 6% |
| Talcum powder | 2 | / | 1% |
| Gross weight | 200 | / | / |
The preparation method of the tolvaptan sustained release preparation of the present embodiment is conventional granulating tabletting process, specific as follows:
According to recipe quantity, first by tolvaptan, hydroxypropyl methylcellulose (50mPas), cornstarch, microcrystalline cellulose and friendship
Join povidone to be uniformly mixed, appropriate purified water granulation is then added, and in 60 DEG C of boiling drier dry 20min, 24 mesh steel sieve
Whole grain obtains particle, and above-mentioned particle is finally mixed 5min with talcum powder in three-dimensional mixer, and discharge simultaneously tabletting, every slice weight
About 200mg(totally 10000).
(embodiment 3)
The tolvaptan sustained release preparation formula of the present embodiment is shown in Table 3.
Table 3
| Ingredient | Single dose mg/ piece | Specifications and models | Weight percent |
| Tolvaptan | 5 | / | 2.5% |
| Hydroxypropyl methylcellulose (50mPas) | 60 | METHOCEL™ E50LV | 30% |
| Hydroxypropyl methylcellulose (10000mPas) | 20 | METHOCEL™ E10M | 10% |
| Lactose | 57 | 200 mesh | 28.5% |
| Microcrystalline cellulose | 50 | PH 101 | 25% |
| Cross-linked carboxymethyl cellulose is received | 6 | / | 3% |
| Colloidal silicon dioxide | 1 | / | 0.5% |
| Magnesium stearate | 1 | / | 0.5% |
| Gross weight | 200 | / | / |
The preparation method of the tolvaptan sustained release preparation of the present embodiment is direct powder compression, specific as follows:
1. first tolvaptan and hydroxypropyl methylcellulose (50mPas and 10000mPas) are placed in three-dimensional mixed according to recipe quantity
15min is mixed in conjunction machine.
2. lactose, microcrystalline cellulose and cross-linked carboxymethyl cellulose is then added to receive, 20min is continuesd to mix.
3. being subsequently added into colloidal silicon dioxide and magnesium stearate, 5min is continuesd to mix.
4. 3. powder that step is mixed to get directly carries out tabletting, every piece weighs about 200mg(totally 10000), finally
It is coated.
(embodiment 4)
The tolvaptan sustained release preparation formula of the present embodiment is shown in Table 4.
Table 4
| Ingredient | Single dose mg/ piece | Specifications and models | Weight percent |
| Tolvaptan | 30 | / | 15% |
| Hydroxypropyl methylcellulose (100mPas) | 50 | METHOCEL™ K100LV | 25% |
| Hydroxypropyl methylcellulose (4000mPas) | 10 | METHOCEL™ K4M | 5% |
| Cornstarch | 48 | 200 mesh | 24% |
| Microcrystalline cellulose | 50 | PH 101 | 25% |
| Low-substituted hydroxypropyl cellulose | 10 | LH-21 | 5% |
| Magnesium stearate | 2 | / | 1% |
| Gross weight | 200 | / | / |
The preparation method of the tolvaptan sustained release preparation of the present embodiment is direct powder compression, specific as follows:
1. first tolvaptan and hydroxypropyl methylcellulose (100mPas and 4000mPas) are placed in three-dimensional mixed according to recipe quantity
15min is mixed in conjunction machine.
2. cornstarch, microcrystalline cellulose and low-substituted hydroxypropyl cellulose is then added, 20min is continuesd to mix.
3. being subsequently added into magnesium stearate, 5min is continuesd to mix.
4. 3. powder that step is mixed to get directly carries out tabletting, every piece weighs about 200mg(totally 10000).
(comparative example 1)
The tolvaptan pharmaceutical formulation of this comparative example is shown in Table 5.
Table 5
| Ingredient | Single dose mg/ piece | Specifications and models | Weight percent |
| Tolvaptan | 15 | / | 7.5% |
| Lactose | 70 | 200 mesh | 35% |
| Microcrystalline cellulose | 100 | PH 101 | 50% |
| Low-substituted hydroxypropyl cellulose | 13 | LH-21 | 6.5% |
| Magnesium stearate | 2 | / | 1% |
| Gross weight | 200 | / | / |
The tolvaptan sustained release preparation of this comparative example the preparation method is as follows:
Tolvaptan, lactose, microcrystalline cellulose and low-substituted hydroxypropyl cellulose is weighed by recipe quantity to be placed in three-dimensional mixer,
After mixing 20min, magnesium stearate is added, mixes 5min, discharge simultaneously tabletting, every slice weight 200mg(totally 10000).
(test case 1)
Respectively to tolvaptan preparation made from tolvaptan sustained release preparation made from 1~embodiment of embodiment 4, comparative example 1 with
And commercial product Su Maika (specification 15mg) carries out drug release determination.
Measuring method is referring to the second method in four general rules of " Chinese Pharmacopoeia " version in 2015,0931 drug release determination method, release
Medium is 0.05%(w/v) SDS aqueous solution, revolving speed 50r/min, sampling time point 1,2,4,6,8,12h the results are shown in Table
6。
Detection method: taking point of release solution, according to ultraviolet-visible spectrophotometry, is measured respectively 268nm's and 350nm
Wavelength absorbance difference calculates the burst size of every tolvaptan.
Table 6
| 1h | 2h | 4h | 6h | 8h | 12h | |
| Embodiment 1 | 18% | 30% | 47% | 64% | 79% | 91% |
| Embodiment 2 | 21% | 37% | 61% | 78% | 92% | 98% |
| Embodiment 3 | 8% | 22% | 37% | 54% | 68% | 82% |
| Embodiment 4 | 16% | 28% | 46% | 65% | 78% | 94% |
| Comparative example 1 | 94% | 97% | 97% | 96% | 95% | 94% |
| Su Maika | 91% | 93% | 94% | 93% | 91% | 90% |
As can be seen from Table 6, tolvaptan sustained release preparation produced by the present invention can be released medicine effectively is sustained from 1h
To 12h, and release is not influenced by preparation process (direct tablet compressing or pelletizing press sheet).
(test case 2)
By tolvaptan sustained release preparation made from 1~embodiment of embodiment 4 and commercial product Su Maika (specification 15mg)
After aluminium bag packaging is respectively adopted, study on the stability is carried out under the acceleration environment of 40 DEG C/RH75%.
Measuring method: being filler with octadecylsilane key, with acetonitrile-water referring to high effective liquid chromatography for measuring
It (500: 500) is mobility, Detection wavelength 254nm, measurement result is shown in Table 7.
Table 7
| Time | 0 month | 1 month | 3 months | 6 months |
| Embodiment 1 | 0.06% | 0.05% | 0.08% | 0.09% |
| Embodiment 2 | 0.05% | 0.06% | 0.07% | 0.07% |
| Embodiment 3 | 0.03% | 0.04% | 0.06% | 0.07% |
| Embodiment 4 | 0.04% | 0.04% | 0.06% | 0.08% |
| Su Maika | 0.05% | 0.06% | 0.07% | 0.09% |
As can be seen from Table 7, tolvaptan sustained release preparation produced by the present invention is related after 6 months compared with commercial product
Substance does not have conspicuousness variation, stable product quality, and is not influenced by preparation process (direct tablet compressing or pelletizing press sheet).
(experimental example)
Tolvaptan sustained release preparation made from embodiment 1 and commercial product Su Maika (specification 15mg) are carried out respectively
The intracorporal pharmacokinetic studies of Beagle dog, the result is shown in Figure 1.
As seen from Figure 1, tolvaptan sustained release preparation of the invention is substantially reduced compared to commercial product Su Maika
Blood concentration Cmax, overcome ordinary preparation take rear Cmax rise it is too fast caused by Serum Na+ concentration quickly increases, is neural
The side effects such as system sequelae and dehydration, hypovolemia.In addition, tolvaptan sustained release preparation of the invention significantly extends
The internal residence time of drug is up to 16h, shows good slow release effect.
Claims (6)
1. a kind of tolvaptan sustained release preparation, it is characterised in that: it is by tolvaptan, hydroxypropyl methylcellulose and excipient system
At the dosage of the hydroxypropyl methylcellulose is the 30%~45% of tolvaptan sustained release preparation total amount, the hydroxypropyl methylcellulose
Range of viscosities is 50mPa s to 10000mPa s；The excipient include one of diluent, disintegrating agent, lubricant or
It is two or more.
2. tolvaptan sustained release preparation according to claim 1, it is characterised in that: the diluent is selected from lactose, crystallite
One of cellulose, cornstarch are two or more；The dosage of the diluent is tolvaptan sustained release preparation total amount
40~60%.
3. tolvaptan sustained release preparation according to claim 1, it is characterised in that: the disintegrating agent is selected from low-substituted hydroxypropyl
One of base cellulose, crospovidone, croscarmellose sodium are two or more；The dosage of the disintegrating agent is
The 3~7% of tolvaptan sustained release preparation total amount.
4. tolvaptan sustained release preparation according to claim 1, it is characterised in that: the lubricant be selected from magnesium stearate,
One of talcum powder, colloidal silicon dioxide are two or more；The dosage of the lubricant is that tolvaptan sustained release preparation is total
Amount is preferably 0.5~5%.
5. the preparation method of tolvaptan sustained release preparation described in one of Claims 1-4, it is characterised in that: first cut down support general
Smooth raw material is pre-mixed with hydroxypropyl methylcellulose；Then the excipient in addition to lubricant is added and continuess to mix, then again
Lubricant is added and continuess to mix, mixed powder is directly finally subjected to tabletting, obtains sustained release preparation.
6. the preparation method of tolvaptan sustained release preparation described in one of Claims 1-4, it is characterised in that: first will be except lubrication
The granulation of appropriate purified water is added in component other than agent after mixing, is then dried, whole grain, be added followed by lubricant into
Row mixing, finally discharging and tabletting, obtain sustained release preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811566088.8A CN109646391A (en) | 2018-12-20 | 2018-12-20 | Tolvaptan sustained release preparation and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811566088.8A CN109646391A (en) | 2018-12-20 | 2018-12-20 | Tolvaptan sustained release preparation and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109646391A true CN109646391A (en) | 2019-04-19 |
Family
ID=66115464
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811566088.8A Pending CN109646391A (en) | 2018-12-20 | 2018-12-20 | Tolvaptan sustained release preparation and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109646391A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102218042A (en) * | 2011-05-26 | 2011-10-19 | 青岛黄海制药有限责任公司 | Sustained release tablet of quetiapine fumarate composition and preparation method of sustained release tablet |
| US20130108697A1 (en) * | 2010-03-04 | 2013-05-02 | Ramakant Kashinath Gundo | Modified release dosage form |
| CN107982268A (en) * | 2017-12-06 | 2018-05-04 | 佛山市腾瑞医药科技有限公司 | A kind of tolvaptan preparation and its application |
-
2018
- 2018-12-20 CN CN201811566088.8A patent/CN109646391A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130108697A1 (en) * | 2010-03-04 | 2013-05-02 | Ramakant Kashinath Gundo | Modified release dosage form |
| CN102218042A (en) * | 2011-05-26 | 2011-10-19 | 青岛黄海制药有限责任公司 | Sustained release tablet of quetiapine fumarate composition and preparation method of sustained release tablet |
| CN107982268A (en) * | 2017-12-06 | 2018-05-04 | 佛山市腾瑞医药科技有限公司 | A kind of tolvaptan preparation and its application |
Non-Patent Citations (3)
| Title |
|---|
| 孟胜男 等: "《药剂学》", 31 January 2016, 中国医药科技出版社, pages: 386 - 171 * |
| 巴雅尔 等: "《医药技术新进展》", 31 August 1997, 中国医药科技出版社, pages: 383 - 384 * |
| 马祥志 等: "《有机化学》", 31 December 2002, 中国医药科技出版社, pages: 437 - 438 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102056589B (en) | Solid pharmaceutical formulations comprising BIBW 2992 | |
| CN101184489A (en) | Pharmaceutical composition | |
| CN102266307B (en) | Valsartan capsules and preparation method thereof | |
| CN106924208A (en) | A kind of compound Dapagliflozin Metformin Extended-release Tablets and preparation method thereof | |
| CN100484574C (en) | Hydrochloric acid cefetamet pivoxil dispersible tablet and method for preparing the same | |
| CN101904825B (en) | Famciclovir dispersible tablet and preparation method thereof | |
| CN109528674A (en) | A kind of Eliquis pharmaceutical composition and preparation method thereof containing hydrophilic version | |
| CN112386580B (en) | Nintedanib medicinal preparation with improved dissolution rate and stability, preparation method and application thereof | |
| CN107998097B (en) | A kind of tablet and preparation method thereof containing olmesartan medoxomil | |
| TWI724534B (en) | Cellulose powder, lozenges and methods for manufacturing lozenges | |
| CN110179796B (en) | Benzofuran derivative composition and preparation method thereof | |
| CN105055362B (en) | A kind of irbesartan and hydrochlorthiazide piece and preparation method thereof | |
| CN109646391A (en) | Tolvaptan sustained release preparation and preparation method thereof | |
| CN103251569A (en) | Capecitabine tablet composition and preparation method thereof | |
| CN103505466B (en) | Solid compound preparation containing metformin hydrochloride and glimepiride and its production and use | |
| CN103284953B (en) | Bicyclol solid preparation and preparation method thereof | |
| CN111000812B (en) | Preparation method of lacosamide tablets | |
| CN107080741A (en) | Pirfenidone sustained release preparation and preparation method | |
| CN106913538A (en) | A kind of Abiraterone acetate sublingual tablets and preparation method thereof | |
| CN107536831A (en) | A kind of composition and preparation method containing vildagliptin and melbine | |
| CN106511291A (en) | Acotiamide hydrochloride controlled release tablet and preparation method thereof | |
| CN112263554B (en) | Lopinavir ritonavir compound tablet and preparation method thereof | |
| CN106913550B (en) | Preparation method of eslicarbazepine acetate tablets | |
| CN105534959B (en) | Tacrolimus slow release preparation and preparation method thereof | |
| CN112535674B (en) | Letrozole tablet and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |