CN103989650A - Orally disintegrating pharmaceutical composition and preparation method thereof - Google Patents
Orally disintegrating pharmaceutical composition and preparation method thereof Download PDFInfo
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- CN103989650A CN103989650A CN201410262240.9A CN201410262240A CN103989650A CN 103989650 A CN103989650 A CN 103989650A CN 201410262240 A CN201410262240 A CN 201410262240A CN 103989650 A CN103989650 A CN 103989650A
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Abstract
The invention relates to an orally disintegrating pharmaceutical composition and a preparation method thereof and belongs to the field of pharmaceutical preparations. Considering the characteristic of bitter taste of hydrobromic acid vortioxetine, the invention provides a method for preparing orally disintegrating tablets which are small in particle size and can cover the bitter taste. The method is realized by mainly adopting the technical scheme, namely the composition is prepared by granulating or directly tabletting pharmaceutical microcapsules, 20-80 weight percent of filling agent, 5-10 weight percent of disintegrating agent, 0.5-2 percent of flavoring agent and 1-2 percent of lubricating agent. The orally disintegrating tablets do not have a grit feeling, sweetening agents such as saccharin sodium salt and Aspartame are not needed to be added into a subsequent tablet prescription, or the flavor of the tablets can be increased by adding a small amount of sweetening agent or essence and flavor according to market requirements, and the medicine content and encapsulation efficiency can meet the industrial large-scale production requirements.
Description
Technical field
The present invention relates to a kind of Orally disintegrating pharmaceutical composition and preparation method thereof, particularly a kind of technical method carries out Orally disintegrating pharmaceutical composition of taste masking and preparation method thereof.
Background technology
Society, under the effect along with rhythm of life growing tension, various pressure, makes patients with depression quantity surprising.The pathogenic factor of depression is mainly central norepinephrine (NE), 5-hydroxy tryptamine (5-HT) and dopamine (DA) content is too low and function of receptors decline in body.The function more complicated of monoamine neurotransmitter in brain, wherein 5-HT seems playing basic role aspect control feel reaction, NE mainly with insomnia, absent minded relevant, DA is more multi-control operation and cognitive function.These neurotransmitteies have again complicated interaction, and joint effect the psychological behavior such as anxiety, anxiety of human body.
Major depressive disorder (MDD) is commonly called depression, is a kind of mental sickness, is characterized in being in a bad mood changing and other symptoms, can disturb the activity of a people's ability to work, sleep, study, diet and enjoyment happiness.People's all one's life is followed in the outbreak of depression conventionally, although some people may only experience once.
Other S&S of major depressive disorder comprise to daily routines lose interest, body weight or diet generation significant change, insomnia or drowsiness (hypersomnia), be on tenterhooks/stroll about (psychomotor agitation), tired increase, compunction or petty and low sense, slowness of thinking or absent minded and suicidal tendency or suicide idea.Major depressive disorder can make us disabling, and allows people's cisco unity malfunction.Because the affect difference of medicine on everyone is very important so can there be multiple treatment to select for patients with depression.
The fertile Xi Ting (Vortioxetine) that replaces is used for the treatment of major depressive disorder, its antidepressant effect mechanism may heavily absorb with inhibition 5-hydroxy tryptamine (5-HT), strengthen central nervous system's serotonin activating activities relevant, chemical name: 1-[2-(2,4-methylbenzene sulfenyl) phenyl] piperazine, molecular structure:
Its medicinal forms is hydrobromate.
There is bitterness if fertile for Xi Ting principal agent in the time preparing oral cavity disintegration tablet, generally need add a large amount of sweeting agents to cover the bitterness of medicine, even if start to feel sweet but can feel subsequently bitter but added a large amount of sweeting agent human body sensories, taking in a large number correctives simultaneously harmful to health.Therefore there are a lot of scholar's research to adopt technique for packing to prepare pastille microcapsule, Physical as fluidized bed coating is prepared micropill or granule, spray drying method is prepared pastille microcapsule and microsphere etc. as physical-chemical process, make again other preparation after being prepared into the granule of bitter drug.In these methods, physicochemical method is applied morely in experimentation, but its producing feasibility is poor; The large production of physical method is comparatively feasible, but the micropill that fluidized bed process makes or grain diameter are larger, in the time that disintegrate is applied, may cause grittiness; The particle diameter that spray-dired method makes is less, although can not cause grittiness at oral cavity disintegration tablet, drug loading and envelop rate are lower.
Oral disintegrated preparation refer to can be in oral cavity the preparation of disintegrate or dissolving rapidly, this type of preparation runs into saliva disintegrate most of dissolving rapidly in oral cavity, just can take without water.Oral cavity disintegration tablet has advantages of solid dosage forms, for example: good stability, accurate dosage, be easy to produce, little Package size, be easy to carry etc. for patient.Oral cavity disintegration tablet also has advantages of liquid dosage form, for example, be easy to take, can as solid dosage forms, may do not occur the danger suffocating because of physical clogging.The commonplace crowd who is suitable for taking oral cavity disintegration tablet comprises child, and old people is bedfast, or disability patient, and the patient of habitual vomiting, also has anhydrous people at one's side.The patient that the application of certain oral cavity disintegration tablet also can extend to those often takes heavy dose of medicine day by day.Oral cavity disintegration tablet can reduce dosage under the prerequisite not affecting the treatment.
Because tablet can be at Orally disintegrating, the rapid dispersing and dissolving of medicine also can be through buccal mucosa, pharyngeal, gastrointestinal region absorption.Therefore, the quick acting of medicine and the bioavailability of Geng Gao are possible.Because the absorption before gastrointestinal can be avoided first pass effect, therefore for those through the obvious medicine of liver metabolism, its dosage can be cut down.
Summary of the invention
The present invention considers the features such as the fertile bitterness for Xi Ting of hydrobromic acid, invent the less preparation method that can cover again bitterness oral cavity disintegration tablet of a kind of particle diameter, in this oral cavity disintegration tablet, can not produce grittiness, simultaneously need to be at the sweeting agent that adds saccharin sodium, aspartame and so in follow-up tablet formulation, or can add minute quantity sweeting agent or essence and flavoring agent increases tablet local flavor according to the market demand, and its content of dispersion and envelop rate can arrive the requirement of industrialized great production.
For achieving the above object, hydrobromic acid of the present invention is fertile has mainly adopted following technical scheme to realize for western spit of fland oral cavity disintegration tablet:
1. hydrobromic acid is fertile is characterized by the filler of pastille microcapsule and percentage by weight 20%～80% for a western orally disintegration tablet, 5%～10% disintegrating agent, and 0.5%～2% correctives, 1%～2% lubricant, adopts granulation or direct compression and get final product.
Described pastille microcapsule is to contain fertile Xi Ting and a kind of water-fast macromolecular material and other the suitable and appropriate plasticizer of replacing of medicine hydrobromic acid.
Described water-fast macromolecular material can be selected hydroxypropyl methyl cellulose phthalate, ethyl cellulose, Lac, CAP, hydroxypropyl methylcellulose acetate succinate, AEA, polyacrylic resin stomach dissolution type, enteric solubility and gastrointestinal swelling type; Optimization polypropylene acid resin stomach dissolution type, enteric solubility and gastrointestinal swelling type; Particularly preferably polyacrylic resin stomach dissolution type.The content of microcapsule principal agent is 10%～60% (w/w).
Described plasticizer can be selected one or more in glycerol, propylene glycol, triacetyl glycerine, citron acid esters, Polyethylene Glycol, phthalic acid ester, dibutyl sebacate; Preferably phthalic acid ester; Particularly preferably diethyl phthalate.
Described pastille microcapsule, its particle diameter is at 10～1000 μ m, and preferable particle size is between 50 μ m～550 μ m.
Described microcapsule preparation method can adopt the conventional packaging technique such as coating in the sedimentation method, fluidized coating, liquid, the preferably sedimentation method, it is characterized in that, a certain proportion of principal agent and polyacrylic resin and plasticizer are dissolved in ethanol, this solution is injected or pours into 0.1M～0.01M sodium hydroxide solution or the pure water solution of quick agitator, stir after certain hour and filter, gained microgranule in baking oven or Minton dryer dry completely after and get final product.
The fertile content (to irrigate for Xi Ting) for western spit of fland microcapsule of described hydrobromic acid is 10～60%, and preferred content is 15%～45% (w/w).
Described filler can be selected saccharide or sugar alcohols and have the amino acids of sweet taste, preferably lactose, sucrose, fructose, oligofructose, glucose, maltose, mannitol, sorbitol, maltose alcohol, xylitol, glycine, alanine, threonine etc., particularly preferably mannitol and lactose or their certain proportion mixture;
Disintegrating agent can be selected two or more mixture of pregelatinized Starch, carboxymethyl starch sodium, sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose (L-HPC), cross-linking sodium carboxymethyl cellulose and they, particularly preferably low-substituted hydroxypropyl cellulose and cross-linking sodium carboxymethyl cellulose or their a certain proportion of mixture;
The essence and flavoring agent of the optional various tastes of correctives, aspartame, stevioside; Lubricant can be selected magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, Pulvis Talci, adipic acid, micropowder silica gel and two or more mixture thereof, particularly preferably magnesium stearate and micropowder silica gel or their a certain proportion of mixture.
The fertile western spit of fland oral cavity disintegration tablet pressure that replaces of hydrobromic acid of the present invention is at 25～40N.
Get 6 test tubes (diameter 1-2cm), respectively add 2ml water, 37 DEG C of insulations, in each test tube, respectively add 1, the tablet that embodiment 1 makes, while adding tablet, start timing, the test tube that overturns after 1 minute, is buckled in 24 eye mesh screens (No. 2 screen clothes) upper, and granule is all by screen cloth (necessary time can with 2-3ml water flushing screen cloth); Adopt volunteer oral method test, all disintegrates and without bitter in 30s; According to dissolution test method (two X C the second methods of Chinese Pharmacopoeia version in 2010) test, be equivalent to the fertile for western spit of fland preparation of 20mg, in 900ml dissolution medium, rotating speed 50rpm/min, the dissolution rate of 30min is more than 90%.Can obtain imperceptible bitterness by technology provided by the invention, there is the hardness of use and the Orally disintegrating time short, imperceptible rough grittiness can guarantee the fertile oral cavity disintegration tablet for Xi Ting and salt thereof of the percentile hydrobromic acid of its stripping while taking.Not only there is patient's taking convenience of obstacle for old-age group or physiology, for the people of the city life busy also drug administration anywhere or anytime.
Detailed description of the invention:
Embodiment 1:
Taking fertile Xi Ting, 20g stomach dissolution type polyacrylic resin EPO, the 1g diethyl phthalate of replacing of 10g hydrobromic acid is dissolved in 20ml dehydrated alcohol, after magnetic agitation dissolving suspendible is even, impouring mixing speed is in the water of 400～600rpm, precipitation completely after, sucking filtration, gained powder be placed in the dry 24h of vacuum drying oven and take out, be placed in the shady and cool place of hermetic container and preserve and obtain the fertile western spit of fland flavor hidden microcapsule that replaces of hydrobromic acid.
Tablet formulation:
| Hydrobromic acid is fertile for western spit of fland flavor hidden microcapsule | 10g (to irrigate for Xi Ting) |
| Mannitol | 100g |
| L-HPC | 15g |
| Lactose | 20g |
| Micropowder silica gel | 1g |
| Magnesium stearate | 1g |
Take above-mentioned material (except magnesium stearate) and pour in three-dimensional mixer and mix, then add magnesium stearate to mix; Mixed material is poured in tablet machine hopper, and adjustment sheet weighs and pressure, carries out tabletting, makes institute's tablet agent hardness remain on 30～50N; The cold forming of two aluminum bubble-cap is packed and be get final product.
Embodiment 2:
Taking fertile Xi Ting, 80g stomach dissolution type polyacrylic resin EPO and the 2g diethyl phthalate of replacing of 20g hydrobromic acid is dissolved in 20ml dehydrated alcohol, after magnetic agitation dissolving suspendible is even, impouring mixing speed is in the water of 400～600rpm, precipitation completely after, sucking filtration, gained powder be placed in the dry 24h of vacuum drying oven and take out, be placed in the shady and cool place of hermetic container and preserve and obtain the fertile western spit of fland flavor hidden microcapsule that replaces of hydrobromic acid.
Tablet formulation:
| Hydrobromic acid is fertile for western spit of fland flavor hidden microcapsule | 10g (to irrigate for Xi Ting) |
| Mannitol | 90g |
| Lactose | 50g |
| Cross-linking sodium carboxymethyl cellulose | 20g |
| Correctives | 1g |
| Magnesium stearate | 1g |
Take above-mentioned material (except magnesium stearate) and pour in three-dimensional mixer and mix, then add magnesium stearate to mix; Mixed material is poured in tablet machine hopper, and adjustment sheet weighs and pressure, carries out tabletting, makes institute's tablet agent hardness remain on 30～50N; The cold forming of two aluminum bubble-cap is packed and be get final product.
Embodiment 3:
Taking fertile Xi Ting, 80g stomach dissolution type polyacrylic resin EPO and the 2g diethyl phthalate of replacing of 20g hydrobromic acid is dissolved in 20ml dehydrated alcohol, after magnetic agitation dissolving suspendible is even, impouring mixing speed is in the water of 400～600rpm, precipitation completely after, sucking filtration, gained powder be placed in the dry 24h of vacuum drying oven and take out, be placed in the shady and cool place of hermetic container and preserve and obtain the fertile western spit of fland flavor hidden microcapsule that replaces of hydrobromic acid.
Tablet formulation:
| Hydrobromic acid is fertile for western spit of fland flavor hidden microcapsule | 20g (to irrigate for Xi Ting) |
| Mannitol | 100g |
| Lactose | 60g |
| Low-substituted hydroxypropyl cellulose (L-HPC) | 25g |
| Correctives | 2g |
| Magnesium stearate | 1g |
Take above-mentioned material (except magnesium stearate) and pour into and in three-dimensional mixer, mix 30min, then add magnesium stearate to mix 1～2min; Mixed material is poured in tablet machine hopper, and adjustment sheet weighs and pressure, carries out tabletting, makes institute's tablet agent hardness remain on 30～50N; The cold forming of two aluminum bubble-cap is packed and be get final product.
Embodiment 4:
Taking fertile Xi Ting, 80g stomach dissolution type polyacrylic resin EPO and the 2g diethyl phthalate of replacing of 20g hydrobromic acid is dissolved in 20ml dehydrated alcohol, after magnetic agitation dissolving suspendible is even, impouring mixing speed is in the water of 400～600rpm, precipitation completely after, sucking filtration, gained powder be placed in the dry 24h of vacuum drying oven and take out, be placed in the shady and cool place of hermetic container and preserve and obtain the fertile western spit of fland flavor hidden microcapsule that replaces of hydrobromic acid.
Tablet formulation:
| Hydrobromic acid is fertile for western spit of fland flavor hidden microcapsule | 20g (to irrigate for Xi Ting) |
| Mannitol | 100g |
| Lactose | 70g |
| Low-substituted hydroxypropyl cellulose (L-HPC) | 15g |
| Correctives | 1g |
| Magnesium stearate | 2g |
Take above-mentioned material (except magnesium stearate) and pour into and in three-dimensional mixer, mix 30min, then add magnesium stearate to mix 1～2min; Mixed material is poured in tablet machine hopper, and adjustment sheet weighs and pressure, carries out tabletting, makes institute's tablet agent hardness remain on 30～50N; The cold forming of two aluminum bubble-cap is packed and be get final product.
Claims (8)
1. a hydrobromic acid is fertile for western orally disintegration tablet; its principal character is the filler it is characterized by pastille microcapsule and percentage by weight 20%～80%, 5%～10% disintegrating agent, 0.5%～2% correctives; 1%～2% lubricant, adopts granulation or direct compression and get final product.
2. oral cavity disintegration tablet according to claim 1, is characterized in that described pastille microcapsule, contains medicine hydrobromic acid fertile for Xi Ting and a kind of water-fast macromolecular material and plasticizer.
3. oral cavity disintegration tablet according to claim 2, is characterized in that described water-fast macromolecular material is hydroxypropyl methyl cellulose phthalate, ethyl cellulose, Lac, CAP, hydroxypropyl methylcellulose acetate succinate, AEA, polyacrylic resin stomach dissolution type, enteric solubility and gastrointestinal swelling type; Optimization polypropylene acid resin stomach dissolution type, enteric solubility and gastrointestinal swelling type; Particularly preferably polyacrylic resin stomach dissolution type; Described plasticizer can be selected one or more in glycerol, propylene glycol, triacetyl glycerine, citron acid esters, Polyethylene Glycol, phthalic acid ester, dibutyl sebacate; Preferably phthalic acid ester; Particularly preferably diethyl phthalate.
4. oral cavity disintegration tablet according to claim 2, is characterized in that described pastille microcapsule, and particle diameter is 10～1000 μ m, preferable particle size 50 μ m～550 μ m.
5. oral cavity disintegration tablet according to claim 2, the preparation method of described microcapsule can adopt the conventional packaging technique such as coating in the sedimentation method, fluidized coating, liquid, the preferably sedimentation method, it is characterized in that, a certain proportion of principal agent and polyacrylic resin and plasticizer are dissolved in ethanol, this solution is injected or pours into 0.1M～0.01M sodium hydroxide solution or the pure water solution of quick agitator, stir after certain hour and filter, gained microgranule in baking oven or Minton dryer dry completely after and get final product.
6. oral cavity disintegration tablet according to claim 1, is characterized in that described pastille microcapsule is 10～60% containing the fertile content (to irrigate for Xi Ting) for western spit of fland microcapsule of hydrobromic acid, and preferred content is 15%～45% (w/w).
7. oral cavity disintegration tablet according to claim 1, it is characterized in that filler can select saccharide or sugar alcohols and have the amino acids of sweet taste, preferably lactose, sucrose, fructose, oligofructose, glucose, maltose, mannitol, sorbitol, maltose alcohol, xylitol, glycine, alanine or threonine, particularly preferably mannitol or lactose or their certain proportion mixture; Disintegrating agent can be selected two or more mixture of pregelatinized Starch, carboxymethyl starch sodium, sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose (L-HPC), cross-linking sodium carboxymethyl cellulose and they, particularly preferably low-substituted hydroxypropyl cellulose and cross-linking sodium carboxymethyl cellulose or their a certain proportion of mixture; The essence and flavoring agent of the optional various tastes of correctives, aspartame, stevioside; Lubricant can be selected magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, Pulvis Talci, adipic acid, micropowder silica gel and two or more mixture thereof, particularly preferably magnesium stearate and micropowder silica gel or their a certain proportion of mixture.
Orally disintegrating according to claim 1 its, it is characterized in that tablet pressure at 25～40N.
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Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104644594A (en) * | 2015-02-03 | 2015-05-27 | 郑州大明药物科技有限公司 | Hydrobromic acid vortioxetine gastric-soluble tablet and preparation method thereof |
| CN104689322A (en) * | 2015-03-24 | 2015-06-10 | 北京化工大学 | Composition containing fluoxertine hydrochloride and enteric acrylic resin and preparation method thereof |
| CN104873458A (en) * | 2015-06-24 | 2015-09-02 | 万特制药(海南)有限公司 | Vortioxetine freeze-dried orally disintegrating tablet and preparation method thereof |
| CN105534933A (en) * | 2016-01-19 | 2016-05-04 | 美吉斯制药（厦门）有限公司 | Vortioxetine orally disintegrating tablet and preparation method thereof |
| CN106176647A (en) * | 2016-08-30 | 2016-12-07 | 佛山市弘泰药物研发有限公司 | A kind of fertile for western spit of fland oral cavity disintegration tablet and preparation method thereof |
| CN106265523A (en) * | 2016-08-30 | 2017-01-04 | 佛山市弘泰药物研发有限公司 | A kind of fertile for western spit of fland nanoparticle, preparation and preparation method thereof |
| CN106361720A (en) * | 2016-08-30 | 2017-02-01 | 佛山市弘泰药物研发有限公司 | Preparation method of vortioxetine soft capsules |
| CN106667941A (en) * | 2017-02-23 | 2017-05-17 | 佛山市弘泰药物研发有限公司 | Vortioxetine orally disintegrating tablet and preparation method thereof |
| CN107789327A (en) * | 2016-09-07 | 2018-03-13 | 成都康弘药业集团股份有限公司 | A kind of pharmaceutical composition containing hydrobromic acid Wo Saiting and preparation method thereof |
| CN112438979A (en) * | 2019-09-04 | 2021-03-05 | 普济生物科技（台州）有限公司 | Vortioxetine hydrobromide-containing coated particles, solid dispersions and formulations for oral taste masking |
| CN115212190A (en) * | 2021-04-20 | 2022-10-21 | 长沙晶易医药科技有限公司 | Taste-masking vortioxetine oral instant film and preparation method thereof |
| CN116589434A (en) * | 2023-05-22 | 2023-08-15 | 山东泰合医药科技有限公司 | Crystal form A of voathiacin and preparation method and application thereof |
| CN116650487A (en) * | 2022-06-27 | 2023-08-29 | 中国人民解放军军事科学院军事医学研究院 | Hydrobromic acid voltammetric acid pharmaceutical composition, preparation method and application thereof |
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| CN101791297A (en) * | 2010-02-10 | 2010-08-04 | 中国药科大学 | Atorvastatin calcium oral disintegrating tablet and preparation method thereof |
| WO2014044721A1 (en) * | 2012-09-19 | 2014-03-27 | Sandoz Ag | Novel crystalline form of vortioxetine hydrobromide |
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| CN101791297A (en) * | 2010-02-10 | 2010-08-04 | 中国药科大学 | Atorvastatin calcium oral disintegrating tablet and preparation method thereof |
| WO2014044721A1 (en) * | 2012-09-19 | 2014-03-27 | Sandoz Ag | Novel crystalline form of vortioxetine hydrobromide |
Cited By (22)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104644594A (en) * | 2015-02-03 | 2015-05-27 | 郑州大明药物科技有限公司 | Hydrobromic acid vortioxetine gastric-soluble tablet and preparation method thereof |
| CN104689322A (en) * | 2015-03-24 | 2015-06-10 | 北京化工大学 | Composition containing fluoxertine hydrochloride and enteric acrylic resin and preparation method thereof |
| CN104873458A (en) * | 2015-06-24 | 2015-09-02 | 万特制药(海南)有限公司 | Vortioxetine freeze-dried orally disintegrating tablet and preparation method thereof |
| CN105534933A (en) * | 2016-01-19 | 2016-05-04 | 美吉斯制药（厦门）有限公司 | Vortioxetine orally disintegrating tablet and preparation method thereof |
| CN106176647A (en) * | 2016-08-30 | 2016-12-07 | 佛山市弘泰药物研发有限公司 | A kind of fertile for western spit of fland oral cavity disintegration tablet and preparation method thereof |
| CN106265523A (en) * | 2016-08-30 | 2017-01-04 | 佛山市弘泰药物研发有限公司 | A kind of fertile for western spit of fland nanoparticle, preparation and preparation method thereof |
| CN106361720A (en) * | 2016-08-30 | 2017-02-01 | 佛山市弘泰药物研发有限公司 | Preparation method of vortioxetine soft capsules |
| CN107789327A (en) * | 2016-09-07 | 2018-03-13 | 成都康弘药业集团股份有限公司 | A kind of pharmaceutical composition containing hydrobromic acid Wo Saiting and preparation method thereof |
| CN107789327B (en) * | 2016-09-07 | 2020-06-02 | 成都康弘药业集团股份有限公司 | Pharmaceutical composition containing vortioxetine hydrobromide and preparation method thereof |
| CN106667941A (en) * | 2017-02-23 | 2017-05-17 | 佛山市弘泰药物研发有限公司 | Vortioxetine orally disintegrating tablet and preparation method thereof |
| CN112438979A (en) * | 2019-09-04 | 2021-03-05 | 普济生物科技（台州）有限公司 | Vortioxetine hydrobromide-containing coated particles, solid dispersions and formulations for oral taste masking |
| WO2021043227A1 (en) * | 2019-09-04 | 2021-03-11 | 普济生物科技（台州）有限公司 | Coated granule, solid dispersion, and preparation containing vortioxetine hydrobromide for oral taste masking |
| CN114796222A (en) * | 2019-09-04 | 2022-07-29 | 普济生物科技（台州）有限公司 | Vortioxetine hydrobromide-containing coated particles, solid dispersions and formulations for oral taste masking |
| CN114931579A (en) * | 2019-09-04 | 2022-08-23 | 普济生物科技（台州）有限公司 | Vortioxetine hydrobromide-containing coated particles, solid dispersions and formulations for oral taste masking |
| JP2022540249A (en) * | 2019-09-04 | 2022-09-14 | シーズンズ バイオテクノロジー （タイジョウ） カンパニー リミテッド | Coated granules, solid dispersions and formulations for oral taste masking containing vortioxetine hydrobromide |
| CN114796222B (en) * | 2019-09-04 | 2024-03-29 | 普济生物科技（台州）有限公司 | Coated granules, solid dispersions and formulations containing vortioxetine hydrobromide for taste masking in the oral cavity |
| CN115212190A (en) * | 2021-04-20 | 2022-10-21 | 长沙晶易医药科技有限公司 | Taste-masking vortioxetine oral instant film and preparation method thereof |
| CN116650487A (en) * | 2022-06-27 | 2023-08-29 | 中国人民解放军军事科学院军事医学研究院 | Hydrobromic acid voltammetric acid pharmaceutical composition, preparation method and application thereof |
| CN116650488A (en) * | 2022-06-27 | 2023-08-29 | 中国人民解放军军事科学院军事医学研究院 | Hydrobromic acid voltammetric acid cetin resin compound, and preparation method and application thereof |
| CN116650488B (en) * | 2022-06-27 | 2024-10-18 | 中国人民解放军军事科学院军事医学研究院 | Hydrobromic acid voltammetric acid cetin resin compound, and preparation method and application thereof |
| CN116650487B (en) * | 2022-06-27 | 2024-10-18 | 中国人民解放军军事科学院军事医学研究院 | Hydrobromic acid voltammetric acid pharmaceutical composition, preparation method and application thereof |
| CN116589434A (en) * | 2023-05-22 | 2023-08-15 | 山东泰合医药科技有限公司 | Crystal form A of voathiacin and preparation method and application thereof |
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Application publication date: 20140820 |