CN1985807A - Compound Desloratadine-Ambroxol oral disintegrated tablet and its preparing method - Google Patents
Compound Desloratadine-Ambroxol oral disintegrated tablet and its preparing method Download PDFInfo
- Publication number
- CN1985807A CN1985807A CNA2006101676676A CN200610167667A CN1985807A CN 1985807 A CN1985807 A CN 1985807A CN A2006101676676 A CNA2006101676676 A CN A2006101676676A CN 200610167667 A CN200610167667 A CN 200610167667A CN 1985807 A CN1985807 A CN 1985807A
- Authority
- CN
- China
- Prior art keywords
- desloratadine
- preparation
- ambroxol
- oral cavity
- mixture
- 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 present invention relates to a kind of compound Desloratadine-Ambroxol oral disintegrated tablet for treating cough accompanied by abnormal secretion and allergic rhinitis and its preparation process. The present invention aims at providing one kind of new Desloratadine-Ambroxol preparation with fast absorption, high bioavailability, simple taking without need of water and no first pass effect of liver. The compound Desloratadine-Ambroxol oral disintegrated tablet is prepared with Desloratadine and Ambroxol as main material and proper amount of supplementary material and through the technological process of the present invention.
Description
Technical field
The present invention relates to a kind ofly be used to alleviate, as sneeze, watery nasal discharge, rhinocnesmus, the compound Desloratadine-Ambroxol oral disintegrating tablet of shedding tears etc. and preparation method thereof with the cough of abnormal secretion thing and the relevant symptom of allergic rhinitis.
Background technology
Ambroxol hydrochloride is the respiratory mucus regulator of a new generation, also is to act on the strongest expectorant at present clinically.Have the superior effect of eliminating the phlegm, and the synthetic and secretion of alveolar surfactant is had significant facilitation.Ambroxol hydrochloride can stimulate the bronchorrhea glandular secretion to be easier to mobile mucus to make sputum dilution, and toughness reduces, and can increase the generation and the secretion of pulmonary surfactant, thereby reduction airway resistance, reduce mucous adhesive force, activate mucociliary blanket function, promote the mucociliary transhipment.Compare with the first generation and second filial generation expelling phlegm drugs, ambroxol hydrochloride is except that having powerful mucolysis effect, and its maximum characteristics are that it can stimulate alveolar type II cells, promotes the synthetic and secretion of alveolar surfactant, thereby effectively strengthen mucus transport, promote expectoration.The main phosphatidylcholine of alveolar surfactant, its fundamental component is a palmitic acid.Ambroxol hydrochloride can impel palmitic acid to take in alveolar type II cells, thereby significantly strengthens the synthetic and secretion of alveolar surfactant.And ambroxol hydrochloride is safe in utilization, and better tolerance is reused no drug accumulation.
Desloratadine is developed by Schering Plough company, obtain European Union's approval listing January calendar year 2001, desloratadine is the interior main active metabolite of the body of loratadine, it is the follow-up medicine of loratadine, and oral desloratadine is 10 to 20 times of the loratadine drug effect approximately, is 2.5 to 4 times of loratadine approximately in the animal body.Desloratadine is similar with the loratadine pharmacological action, has selectivity and suppresses periphery H
1The effect of receptor, no maincenter sedation and cholinolytic effect, the clinical allergic rhinitises that are used for the treatment of more.Itch and burn feeling for alleviating symptom such as sneeze, watery nasal discharge and rhinocnesmus, nasal obstruction and the eye that can close with allergic rhinitis, clinical effectiveness is good.Behind the oral administration, nose and eye symptom and sign are able to rapid alleviation, also are applicable to the relieve chronic urticaria, ooze the symptom and the sign of itching skin disease and other anaphylaxis dermatosis.Have long-acting, brute force and compete peripheral H1-receptor specifically, the effect of blocking histamine.
Oral cavity disintegration tablet is a kind of new pharmaceutical dosage forms, is that a kind of water that do not need in the oral cavity can disintegrate or dissolved tablet.It can be in the oral cavity rapidly disintegrate, no grittiness, good mouthfeel, swallow easily, to the oral mucosa nonirritant.The distinguishing feature of this dosage form: 1. absorption is fast, bioavailability is high; 2. instructions of taking does not need water, makes things convenient for part crowd medication, as the patient's medication under old man, child, dysphagia or the special environment; 3. intestinal is residual few, few side effects; 4. avoid the first pass effect of liver sausage.
By retrieval, do not see the pertinent literature and the patent report of relevant compound Desloratadine-Ambroxol oral disintegrating tablet.
Summary of the invention
The purpose of this invention is to provide a kind of disintegrate fast, absorb rapidly, can effectively improve the bioavailability and the blood drug level of active constituents of medicine, improve compound Desloratadine-Ambroxol oral disintegrating tablet of the special bitter in the mouth of ambroxol hydrochloride, taking convenience and preparation method thereof simultaneously.
Compound Desloratadine-Ambroxol oral disintegrating tablet of the present invention also contains adjuvant except principal agent.Adjuvant is any available adjuvant that is fit to make oral cavity disintegration tablet, and they can comprise filler, disintegrating agent, effervescent, correctives or odor mask, binding agent, lubricant etc.In each oral formulations unit, the amount that contains desloratadine is 1.25-20mg, is preferably 2.5-10mg, and the amount that contains the active ingredient hydrochloric acid ambroxol is 10-90mg.Be preferably 20-60mg.The ratio of two kinds of active component is 1: 24-2: 3.
The amount that each preparation unit of the present invention contains the active component desloratadine is 5mg more preferably, and the amount of ambroxol hydrochloride is 30mg more preferably.The ratio of two kinds of active component more preferably 1: 6.
Because oral cavity disintegration tablet requires disintegrate rapidly in the oral cavity, good mouthfeel, to the oral mucosa nonirritant.Therefore the selection to supplementary product kind and performance thereof is the key of preparation oral cavity disintegration tablet.
The present invention is through selecting, found the pharmaceutic adjuvant of suitable compound Desloratadine-Ambroxol oral disintegrating tablet, wherein filler selects to be used for increasing the weight and volume of oral cavity disintegration tablet, so that the molding of preparation and divided dose, the preferred mixture of one or more in starch, lactose, dextrin, microcrystalline Cellulose, sucrose, fructose, mannitol, pregelatinized Starch, sorbitol, xylitol etc. of filler among the present invention.
The kind of disintegrating agent and the selection of consumption are for can this preparation disintegrate be most important fully at the appointed time.Disintegrating agent of the present invention selects to comprise a kind of or wherein several mixture in low-substituted hydroxypropyl cellulose, crospolyvinylpyrrolidone, cross-linking sodium carboxymethyl cellulose, crosslinked carboxymethyl fecula sodium, pregelatinized Starch, the carboxymethyl starch sodium.
In oral cavity disintegration tablet, can add an amount of effervescent, help the disintegrate of tablet, and an amount of acid can also be regulated taste.Acid source is selected from citric acid, tartaric acid, four mixture of one or more in acid, lysine, the arginine in the effervescent that the present invention selects, and alkali source is selected from one or more mixture wherein such as sodium bicarbonate, sodium carbonate, potassium carbonate, potassium bicarbonate.
When the weight percent of principal agent in preparation is higher, owing to bitterness may occur, therefore can select to add an amount of odor mask increasing patient tolerability, odor mask of the present invention comprises one or more the mixture in acrylic resin copolymer, Magnesiumaluminumsilicate, gelatin, melon glue, arabic gum, xanthan gum, hard paraffin, the Brazil wax.
The correctives that the present invention uses is selected from one or more the mixture in Rhizoma et radix valerianae, Fructus Pruni pseudocerasi, Fructus Vitis viniferae, Fructus Citri tangerinae, Fructus Citri Limoniae, Herba Menthae, Fructus Fragariae Ananssae, Fructus Musae, Fructus Ananadis comosi, honey peach essence, maltose alcohol, saccharin sodium, protein sugar, sucrose, Mentholum, aspartame, stevioside, the acesulfame-K.
Preparation and molding for the ease of preparation have added binding agent and lubricant.Binding agent is selected from one or more the mixture in syrup, starch slurry, carboxymethylcellulose sodium solution, HPMC solution, the povidone solution.Lubricant is selected from one or more the mixture in micropowder silica gel, magnesium stearate, PEG6000, the Pulvis Talci.
Oral cavity disintegration tablet of the present invention can be by freeze-drying or direct powder compression or granulating tabletting process preparation.
Adopt freeze-drying to prepare oral cavity disintegration tablet, adjuvant can be chosen filler, disintegrating agent, correctives and odor mask (selective), compound Desloratadine-Ambroxol can be mixed with various adjuvants, add the suitable quantity of water dilution, behind the mix homogeneously, place suitable sheet shape mould, lyophilization, being shaped to the material lyophilizing gets final product.
Adopt direct powder compression to prepare oral cavity disintegration tablet, adjuvant can be chosen filler, disintegrating agent, effervescent, lubricant, correctives and odor mask, and behind desloratadine, ambroxol hydrochloride and various adjuvant mix homogeneously, direct powder compression gets final product.
Adopt granulating tabletting process to prepare oral cavity disintegration tablet, adjuvant can be chosen filler, disintegrating agent, binding agent, lubricant, correctives and odor mask, with desloratadine, ambroxol hydrochloride and partial supplementary material mix homogeneously, add binding agent system soft material, granulate dry, granulate, the disintegrating agent and the lubricant of adding surplus, behind the mix homogeneously, tabletting gets final product.
Adopt granulating tabletting process to prepare oral cavity disintegration tablet, adjuvant can be chosen filler, disintegrating agent, effervescent, binding agent, lubricant, correctives and odor mask, the main method step is: acid source in the effervescent and alkali source can be separated granulation, or acid source mixed with alkali source, adopt dehydrated alcohol to granulate, dry, granulate, the disintegrating agent and the lubricant of adding surplus as binding agent, behind the mix homogeneously, tabletting gets final product.
The specific embodiment
Come compound Desloratadine-Ambroxol oral disintegrating tablet of the present invention done further specifying by following example, but be not limited in following example.
Embodiment 1
Prescription:
| Desloratadine | 5g |
| Ambroxol hydrochloride Ac-Di-Sol microcrystalline cellulose sweet mellow wine gelatin Aspartame is made altogether | 1000 of 30g 20g 30g 20g 15g 7g |
Preparation method:
Gelatin is dissolved in the suitable quantity of water, obtains heavy-gravity aqueous gelatin solution, add desloratadine, ambroxol hydrochloride, after stirring, continue to add other adjuvants such as cross-linking sodium carboxymethyl cellulose, stir, obtain uniform suspension, be poured in the suitable mould, freezing rapidly, drying under reduced pressure, delivery, press seal, packing.
Embodiment 2
Prescription:
| Desloratadine | 5g |
| The micropowder silica gel of ambroxol hydrochloride microcrystalline Cellulose PPVP honey peach essence is made altogether | 1000 of 30g 170g 12g 8g 5g |
Preparation method:
Desloratadine, ambroxol hydrochloride are all crossed 80 mesh sieves, get loratadine, with the 50g microcrystalline Cellulose according to the equivalent method mix homogeneously that progressively increases; make soft material in right amount with purified water; granulate, drying, standby; other gets ambroxol hydrochloride and surplus microcrystalline Cellulose mix homogeneously; granulate with method, two kinds of granules mix, and add honey peach essence, PPVP, micropowder silica gel mix homogeneously; tabletting gets final product.
Embodiment 3
Prescription:
| Desloratadine | 5g |
| Ambroxol hydrochloride microcrystalline Cellulose low-substituted hydroxypropyl cellulose Eudragit E PO | 30g 75g 7g 30g |
| The Fructus Citri sinensis powdered flavor is made altogether | 1000 of 3g |
Preparation method:
Get ambroxol hydrochloride, the Eudragit E PO mix homogeneously with recipe quantity places baking oven, and attemperation to 95 ℃ fully fuses the two, puts coldly, and porphyrize is crossed 60 mesh sieves, with loratadine according to the equivalent method mix homogeneously that progressively increases; Other gets low-substituted hydroxypropyl cellulose, microcrystalline Cellulose, Fructus Citri sinensis powdered flavor and joins wherein, behind the mix homogeneously, and direct powder compression.
Embodiment 4
Prescription:
| Desloratadine | 5g |
| Ambroxol hydrochloride lactose sweet mellow wine L-HPC sodium carbonate sodium acid carbonate tartaric acid orange flavor dolomol is made altogether | 1000 of 30g 25g 140g 30g 1g 4g 3g 5g 5g |
Preparation method:
With all cross 80 mesh sieves desloratadine, ambroxol hydrochloride, lactose, 35% mannitol, sodium bicarbonate, sodium carbonate, partly measure the L-HPC mix homogeneously approximately, with 50% ethanol liquid system soft material, granulation, drying, granulate; Other gets surplus 65% mannitol, adds tartaric acid, partly measures L-HPC, and mix homogeneously with 50% ethanol liquid system soft material, is granulated, and dry, granulate behind two kinds of granule mix homogeneously, add orange flavor, magnesium stearate outward, and tabletting behind the mix homogeneously gets final product.
Claims (10)
1. a compound Desloratadine-Ambroxol oral disintegrating tablet is characterized in that, said preparation is made up of active component desloratadine, ambroxol hydrochloride and suitable pharmaceutic adjuvant.
2. the compositions of claim 1, the amount that described each preparation unit contains the active component desloratadine is 1.25-20mg, is preferably 2.5-10mg, the amount that contains the active ingredient hydrochloric acid ambroxol is 10-90mg.Be preferably 20-60mg.The ratio of two kinds of active component is 1: 24-2: 3.
3. the compositions of claim 1, the amount that described each preparation unit contains the active component desloratadine is 5mg more preferably, and the amount that contains the active ingredient hydrochloric acid ambroxol is 30mg more preferably.The ratio of two kinds of active component more preferably 1: 6.
4. the described oral cavity disintegration tablet of claim 1 is characterized in that, the described excipient substance that is fit to make oral cavity disintegration tablet comprises one or more in filler, disintegrating agent, effervescent, correctives, odor mask, binding agent or the lubricant etc.
5. the described oral cavity disintegration tablet of claim 3 is characterized in that described filler is selected from one or more the mixture in starch, lactose, dextrin, microcrystalline Cellulose, sucrose, fructose, mannitol, pregelatinized Starch, sorbitol, the xylitol.Described disintegrating agent is selected from a kind of or wherein several mixture in low-substituted hydroxypropyl cellulose, crospolyvinylpyrrolidone, cross-linking sodium carboxymethyl cellulose, crosslinked carboxymethyl fecula sodium, pregelatinized Starch, the carboxymethyl starch sodium.Acid source is selected from one or more the mixture in citric acid, tartaric acid, four caproic acids, lysine, the arginine in the described effervescent, and alkali source is selected from one or more mixture wherein such as sodium bicarbonate, sodium carbonate, potassium carbonate, potassium bicarbonate.Described odor mask is selected from one or more the mixture in acrylic resin copolymer, Magnesiumaluminumsilicate, gelatin, several glue of melon, arabic gum, xanthan gum, hard paraffin, the Brazil wax.Described binding agent is selected from one or more the mixture in syrup, starch slurry, carboxymethylcellulose sodium solution, HPMC solution, the povidone solution; Described lubricant is selected from one or more the mixture in micropowder silica gel, magnesium stearate, PEG6000, the Pulvis Talci.Described correctives one of is selected from Rhizoma et radix valerianae, Fructus Pruni pseudocerasi, Fructus Vitis viniferae, Fructus Citri tangerinae, Fructus Citri Limoniae, Herba Menthae, Fructus Fragariae Ananssae, Fructus Musae, Fructus Ananadis comosi, honey peach essence, maltose alcohol, saccharin sodium, protein sugar, sucrose, aspartame, stevioside, the acesulfame-K or wherein several mixture.
6. the preparation method of the oral cavity disintegration tablet of claim 1 is characterized in that, adopts the preparation of freeze-drying or direct powder compression or granulating tabletting process.
7. the preparation method of the described oral cavity disintegration tablet of claim 6, wherein the preparation process of freeze-drying is: active constituents of medicine desloratadine, ambroxol hydrochloride and other adjuvant are added the suitable quantity of water dilution, behind the mix homogeneously, place suitable sheet shape mould, lyophilization to material lyophilizing is shaped.
8. the preparation method of the described oral cavity disintegration tablet of claim 6, wherein the direct powder compression preparation process is: behind mix homogeneously such as desloratadine, ambroxol hydrochloride and filler, disintegrating agent, effervescent, lubricant, correctives and odor mask, adopt direct powder compression to be prepared.
9. the preparation method of the described oral cavity disintegration tablet of claim 6, wherein the granulating tabletting process preparation process is: with compound recipe desloratadine, ambroxol hydrochloride and part disintegrating agent, effervescent, filler, correctives and odor mask, add binding agent system soft material, granulate, dry, granulate, the disintegrating agent and the lubricant that add surplus, behind the mix homogeneously, tabletting.
10. the described preparation method of claim 9, it is characterized in that, the step that wherein adds effervescent is, acid source in the effervescent and alkali source are separated granulation, or acid source is mixed with alkali source, adopt dehydrated alcohol to granulate as binding agent, in dry, granulate, the disintegrating agent and the lubricant that add surplus, behind the mix homogeneously, tabletting.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006101676676A CN1985807A (en) | 2006-11-21 | 2006-12-21 | Compound Desloratadine-Ambroxol oral disintegrated tablet and its preparing method |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200610114679 | 2006-11-21 | ||
| CN200610114679.2 | 2006-11-21 | ||
| CNA2006101676676A CN1985807A (en) | 2006-11-21 | 2006-12-21 | Compound Desloratadine-Ambroxol oral disintegrated tablet and its preparing method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1985807A true CN1985807A (en) | 2007-06-27 |
Family
ID=38182834
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2006101676676A Pending CN1985807A (en) | 2006-11-21 | 2006-12-21 | Compound Desloratadine-Ambroxol oral disintegrated tablet and its preparing method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1985807A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102058480A (en) * | 2009-11-17 | 2011-05-18 | 天津天士力制药股份有限公司 | Oral effervescent tablet and preparation method thereof |
| CN103301467A (en) * | 2013-06-20 | 2013-09-18 | 北京阜康仁生物制药科技有限公司 | Stable taste-masking ambroxol hydrochloride compound and preparation method thereof |
| CN104324383A (en) * | 2014-09-28 | 2015-02-04 | 南京泽恒医药技术开发有限公司 | Diphenhydramine hydrochloride drug composition and preparation method thereof |
-
2006
- 2006-12-21 CN CNA2006101676676A patent/CN1985807A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102058480A (en) * | 2009-11-17 | 2011-05-18 | 天津天士力制药股份有限公司 | Oral effervescent tablet and preparation method thereof |
| CN102058480B (en) * | 2009-11-17 | 2014-07-23 | 天士力制药集团股份有限公司 | Oral effervescent tablet and preparation method thereof |
| CN103301467A (en) * | 2013-06-20 | 2013-09-18 | 北京阜康仁生物制药科技有限公司 | Stable taste-masking ambroxol hydrochloride compound and preparation method thereof |
| CN104324383A (en) * | 2014-09-28 | 2015-02-04 | 南京泽恒医药技术开发有限公司 | Diphenhydramine hydrochloride drug composition and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1709229A (en) | Memantine hydrochloride orally disintegrating tablet and its preparing method | |
| CN101647805B (en) | Glucosamine chewable tablet used for relieving and preventing osteoarthritis and preparation method thereof | |
| CN102198110A (en) | Tenofovir disoproxil fumarate dispersible tablets and preparation method thereof | |
| CN1872217B (en) | A medication for treating headache, and preparation method | |
| JP2013533881A (en) | Pharmaceutical composition containing vanoxerin | |
| CN101564402A (en) | Rehabilitation new dispersing tablet and preparation method thereof | |
| CN103070865A (en) | Oral solid preparation taking prucalopride succinate as active ingredient and application of oral solid preparation | |
| CN102631329A (en) | Oral paroxetine disintegrating tablet and preparation process thereof | |
| CN100374119C (en) | Pseudo-ginseng saponin oral disintegration tablet and preparing method | |
| CN101904827A (en) | Orally disintegrating tablet of ambroxol hydrochloride and preparation method thereof | |
| CN101401796A (en) | Pramipexole orally disintegrating tablets and preparation method thereof | |
| CN101264080A (en) | Pharmaceutical composition containing dexchlorpheniramine and preparation thereof | |
| CN1985807A (en) | Compound Desloratadine-Ambroxol oral disintegrated tablet and its preparing method | |
| CN1302772C (en) | Orally disintegrated sodium ferulate tablet and its prepn process | |
| CN100496515C (en) | Ring form effervescence dosage and preparation method thereof | |
| CN101305988A (en) | Compound alendronate sodium vitamine D3 orally disintegrating tablets and preparation method thereof | |
| CN101822646A (en) | Fexofenadine hydrochloride orally disintegrating tablet and preparation method thereof | |
| CN103156817A (en) | Rizatriptan drug absorbed through mouth mucosa | |
| CN1994304A (en) | Compound orally disintegrating tablet containing loratadine and ambroxol and preparation process thereof | |
| CN100450470C (en) | Rapid disintegrate tablet in oral and its preparation method | |
| CN101120928B (en) | Vitamin K1 orally disintegrating tablets preparation and preparation method thereof | |
| CN104257611B (en) | Pharmaceutical composition containing micronized fexofenadine hydrochloride | |
| CN100536829C (en) | Erigeron breviscapus oral caving fast disintegration tablet and its preparation method | |
| CN103156816A (en) | Almotriptan drug absorbed through mouth mucosa | |
| CN101269055A (en) | Ambroxol hydrochloride oral cavity disintegrating tablet and method of producing the same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20070627 |