CN102614159B - Ambroxol hydrochloride composition - Google Patents
Ambroxol hydrochloride composition Download PDFInfo
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- CN102614159B CN102614159B CN 201210029057 CN201210029057A CN102614159B CN 102614159 B CN102614159 B CN 102614159B CN 201210029057 CN201210029057 CN 201210029057 CN 201210029057 A CN201210029057 A CN 201210029057A CN 102614159 B CN102614159 B CN 102614159B
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Abstract
The invention discloses an ambroxol hydrochloride composition, and relates to the technical field of pharmaceutical preparations. The formula of the composition comprises a main drug and adjuvants, wherein the main drug is ambroxol hydrochloride, the adjuvants comprise a skeleton agent, a forming agent, an assistant suspending agent, a correctant, and a disintegrating agent, the skeleton agent is selected from lactose, the forming agent is selected from gelatin, the assistant suspending agent is selected from povidone K30, the correctant is selected from aspartame, and the disintegrating agent is selected from cross-linked povidone. In addition, freeze-dried orally disintegrating tablets of the ambroxol hydrochloride composition have the following characteristics that: the components are simple; no water is required during taking; no chewing is required; the disintegrating time in the human oral cavity is less than 2 seconds; the onset is rapid; the residue in the intestinal tract is less; the absorption is adequate; the side effect is low; the taste is good; the tablets are especially suitable for infant patient taking. The present invention further provides a preparation method for the freeze-dried orally disintegrating tablets of the ambroxol hydrochloride composition, wherein the method has characteristics of mild conditions and easy control, and is suitable for large-scale industrial production.
Description
Technical field
The present invention relates to technical field of medicine, be specifically related to a kind of ambroxol hydrochloride composition and contain a kind of ambroxol hydrochloride composition freeze-dry orally disintegrating tablet that above-mentioned composition makes and preparation method thereof.
Background technology
Ambroxol hydrochloride is the new activated product that a kind of ambroxol merges HCL and salify, it is a kind of new mucolytic drugs, have dissolving secretion mucus and promote the effect that mucus is got rid of, the formation of respiratory tract interfacial agent be can stimulate simultaneously and serosity and mucous secretion regulated, improve the elimination effect in respiratory tract cilium district and fibre-less district, reduce the adhesion strength of sputum and cilium, further make the easy expectoration of expectorant, reach remarkable expectoration, alleviate cough, improve breath state.Its toxicity is low, eliminates the phlegm and to improve the pulmonary function effect strong, and be one of the most frequently used expelling phlegm drugs, clinically be mainly used in reducing phlegm, the aspect such as anti-inflammatory.
The chemical name of ambroxol hydrochloride is the Ambroxol hydrochlorate; Molecular formula: C13H18Br2N2OHCL; Molecular weight: 414.57; Its structural formula is as follows:
Oral cavity disintegration tablet is a kind of quick-effective preparation that development in recent years is got up, it is taken Shi Buxu drinking-water or only need drink a small amount of water, also need not to chew, place and meet i.e. rapidly dissolving or the disintegrate of saliva on the tongue, borrow swallowing act to enter the stomach onset, without mucosa absorption, the interior behavior of body is consistent with conventional tablet, for the patient provides a kind of new administrated method in the oral cavity.Its scope of application is except with ordinary tablet is identical, also is specially adapted to the geologist of dysphagia person (such as old man, child) or field work drinking-water inconvenience and desert area people etc., and also the medical treatment for special circumstances provides convenience.Because its distinctive advantage more and more receives people's concern.Its normal disintegrating agent that adds has crosslinked sodium carboxymethylcellulose pyce, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose sodium, polyvinylpolypyrrolidone etc., adds in addition correctives such as sucrose, Herba Menthae, aspartame, flavorant etc.
Freeze-dry orally disintegrating tablet is a kind of on the basis of oral cavity disintegration tablet, by improving preparation technology, the more efficiently peroral dosage form that suitable children's, the old people garment that obtains used.Specification requirement: 1. good mouthfeel, outward appearance are even; 2. disintegration time should be in 1.2 seconds; 3. other should meet the requirement of tablet general rule.
Ambroxol hydrochloride began clinical practice in 1981 in Germany, in the clinical application of China since 1991, at present, there be oral liquid, tablet, capsule, slow-release pill and the injection kind of ambroxol hydrochloride in the domestic and international market, wherein the tablet specification has 15mg/ sheet and two kinds of specifications of 30mg/ sheet, capsule has 25mg/ grain, 30mg/ grain, three kinds of specifications of 75mg/ grain, and its freeze-dry orally disintegrating tablet dosage form is still waiting development.
The conventional tablet disintegration time of ambroxol hydrochloride is longer, child, old man's dysphagia, and it is poor etc. that the patient takes inconvenience, compliance, affected the performance of ambroxol hydrochloride therapy effect.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of composition simple, easily manufactured, rapid-action ambroxol hydrochloride composition and contain ambroxol hydrochloride composition freeze-dry orally disintegrating tablet that above-mentioned composition makes and preparation method thereof.
Technical problem to be solved by this invention realizes by the following technical solutions.
A kind of ambroxol hydrochloride composition, the prescription of said composition is made of principal agent and accessory drugs, it is characterized in that: wherein principal agent is ambroxol hydrochloride, and accessory drugs includes skeleton agent, forming agent, suspending agent, correctives, disintegrating agent;
Lactose is selected in described skeleton agent, and described forming agent is selected gelatin, and described suspending agent is selected PVP K30, and described correctives is selected aspartame, and described disintegrating agent is selected polyvinylpolypyrrolidone;
Wherein principal agent and accessory drugs by weight the prescription total amount in shared ratio be:
Described compositions preferably includes following composition:
Another object of the present invention provides a kind of above-mentioned ambroxol hydrochloride composition freeze-dry orally disintegrating tablet to ambroxol hydrochloride composition that contains, this freeze-dry orally disintegrating tablet component is simple, need not water when taking, need not to chew, disintegration time was no more than for 2 seconds in human oral cavity, rapid-action, intestinal is residual few, absorbs fully, and side effect is low, mouthfeel is good, is particularly suitable for the infant patient and takes.
A kind of ambroxol hydrochloride composition freeze-dry orally disintegrating tablet that contains above-mentioned ambroxol hydrochloride composition, its composition by following weight ratio is prepared from:
Described ambroxol hydrochloride composition freeze-dry orally disintegrating tablet, it preferably is prepared from by following composition:
Described ambroxol hydrochloride composition freeze-dry orally disintegrating tablet specification is 5mg/ sheet or 15mg/ sheet or 30mg/ sheet.
A further object of the present invention provides a kind of preparation method of ambroxol hydrochloride composition freeze-dry orally disintegrating tablet, and the method preparation condition is gentle, is easy to control, is fit to industrialized great production.
For realizing a further object of the present invention, a kind of preparation method of ambroxol hydrochloride composition freeze-dry orally disintegrating tablet adopts following technical scheme:
A) PVP K30, polyvinylpolypyrrolidone, lactose, the aspartame of recipe quantity is dissolved in respectively in the purified water of 10%-15% of prescription water total amount, the gelatin of recipe quantity is joined in the purified water of 10%-15% of prescription water total amount, under stirring, be heated to the boiling dissolving, the ambroxol hydrochloride of recipe quantity is dissolved in the purified water of prescription water consumption 25%-30%, merge each former, auxiliary material liquid, continue to stir 3 hours, measure PH, regulate PH to 6.0 with the hydrochloric acid solution of 2mol/L;
B) according to ambroxol hydrochloride composition freeze-dry orally disintegrating tablet specification, after determining loading amount, medicinal liquid after merging is moved in the drug-containing dish by loading amount, and put into freeze drying box, medicinal liquid is carried out freezing (cryogenic temperature is-20 ℃--50 ℃), evacuation dry (baking temperature is at+5 ℃-+20 ℃, and vacuum is 0.1 handkerchief-20 handkerchief), the control moisture is no more than 1.0%;
C) after ambroxol hydrochloride composition freeze-dry orally disintegrating tablet drying, in freeze drying box, seal;
D) will cut drug-containing dish behind the medicament taking-up freeze drying box that freeze, and carry out finished product packing.
We have formulated relevant detection method for the disintegration rate and bioavailability of ambroxol hydrochloride composition freeze-dry orally disintegrating tablet:
1, disintegration
According to inspection technique disintegration (two appendix x of Chinese Pharmacopoeia version in 2010 A), the stainless steel shaft of hanging basket by the upper end hung on the metal rack, immerse in the 1000ml beaker, and when regulating the hanging basket position it being descended screen cloth apart from beaker bottom 25mm, fill temperature in the beaker and be 37 ℃ ± 1 ℃ water, screen cloth is at underwater 15mm place when regulating height of water level hanging basket being risen.
Except as otherwise herein provided, get 6 groups of test samples (every group of dosage is 90mg), be set up respectively in the glass tubing of stating hanging basket, add baffle plate, start disintegration tester and check, each sheet all should all disintegrates in 1.1 seconds.
Result such as following table:
Dosage equates, disintegration time and the medicine of different ambroxol hydrochloride tablets reach peak concentration
2, bioavailability index of correlation
18 men's health volunteers, year at age (23 ± 1.5), height (169 ± 2.5) cm, body weight (62.5 ± 2.5) kg.The front health check-up of test is all normal, obtains Ethics Committee's approval, and the volunteer is at the tested front Informed Consent Form of all signing.Test adopt binary cycle, opening, at random, the research method of crossover contrast.18 routine experimenters are divided into 3 groups at random, take respectively ambroxol hydrochloride for test preparation or reference preparation 90mg, in taking medicine before (0h) and take medicine afterwards 0.25,0.5,1,1.5,2,3,4,6,9,12,15,24h gathers in veins of upper extremity blood 4mL to the 10ml heparinization test tube,, add 1.5ml chromatograph methanol (containing internal standard substance), high speed centrifugation (3000r/min) 10min behind the whirlpool concussion 2min, separation of supernatant is drawn 20 μ l sample introductions, measures the concentration of ambroxol hydrochloride in the blood plasma.
Average drug-time curve was seen Fig. 1 after 18 routine experimenter's single oral ambroxol hydrochlorides were subjected to test preparation or reference preparation equal dose, showed the interior pharmacokinetics similar process of body of two preparations.
18 routine experimenter's single oral ambroxol hydrochlorides are seen the following form by test preparation or reference preparation equal dose (90mg) artifact availability index of correlation parameter:
Ambroxol Hydrochloride Tablets is subjected to the pharmacokinetic parameter of test preparation and reference preparation
The Orally disintegrating tablet of ambroxol hydrochloride that the disintegration rate that can find out ambroxol hydrochloride composition freeze-dry orally disintegrating tablet of the present invention from above experimental result is made than ambroxol hydrochloride ordinary tablet, traditional pressing is fast, and the Orally disintegrating tablet of ambroxol hydrochloride of ambroxol hydrochloride composition freeze-dry orally disintegrating tablet bioavailability index of correlation of the present invention and ordinary tablet, the manufacturing of traditional pressing is without significant difference.
Because ambroxol hydrochloride composition freeze-dry orally disintegrating tablet of the present invention is main in order to satisfy child's medication demand, has added the correctives aspartame in prescription.
The present invention has following beneficial effect:
The first disintegrate is rapid, and drug effect is fast.Ambroxol hydrochloride composition freeze-dry orally disintegrating tablet of the present invention is rapidly disintegrate in 2 seconds in mouth, is beneficial to the rapid stripping of medicine, shortens dissolution time, accelerates to absorb, and makes its fast performance curative effect.
The second drug absorption is abundant.Ambroxol hydrochloride composition freeze-dry orally disintegrating tablet of the present invention is fully disintegrate in the oral cavity, makes the absorption of medicine more abundant, is conducive to like this improve the bioavailability of medicine.
The 3rd taking convenience, mouthfeel is good.Ambroxol hydrochloride composition freeze-dry orally disintegrating tablet of the present invention needn't be used water delivery service, and saliva can make its complete disintegrate, and foreign sense in mouthful is owing to wherein add the compliance that the sweet child of being conducive to of suitable correctives cool taste flavor takes medicine.Compare with liquid preparation and accurately advantage of dosage arranged.
Description of drawings
Fig. 1 is the average drug-time curve that Ambroxol Hydrochloride Tablets of the present invention is subjected to test preparation and reference preparation.
The specific embodiment
For technological means, creation characteristic that the present invention is realized, reach purpose and effect is easy to understand, below in conjunction with specific embodiment, further set forth the present invention.
Embodiment 1
Preparation ambroxol hydrochloride composition freeze-dry orally disintegrating tablet,
Prescription: 1000 amounts
Preparation technology:
PVP K30 with recipe quantity, polyvinylpolypyrrolidone, lactose, aspartame is dissolved in respectively in the purified water of 10%-15% of prescription water total amount, the gelatin of recipe quantity is joined in the purified water of 10%-15% of prescription water total amount, under stirring, be heated to the boiling dissolving, the ambroxol hydrochloride of recipe quantity is dissolved in the purified water of prescription water consumption 25%-30%, it is former to merge each, auxiliary material liquid, continue to stir 3 hours, measure PH, hydrochloric acid solution with 2mol/L is regulated PH to 6.0, according to ambroxol hydrochloride composition freeze-dry orally disintegrating tablet specification, after determining loading amount, the medicinal liquid after merging is pressed in the loading amount packing drug-containing dish, and put into freeze drying box, carry out freezing to medicinal liquid, after ambroxol hydrochloride composition freeze-dry orally disintegrating tablet drying, in freeze drying box, seal cutting after taking out, packing.
Embodiment 2
Preparation ambroxol hydrochloride composition freeze-dry orally disintegrating tablet,
Prescription: 1000 amounts
Prescription: 1000 amounts
Preparation technology:
PVP K30 with recipe quantity, polyvinylpolypyrrolidone, lactose, aspartame is dissolved in respectively in the purified water of 10%-15% of prescription water total amount, the gelatin of recipe quantity is joined in the purified water of 10%-15% of prescription water total amount, under stirring, be heated to the boiling dissolving, the ambroxol hydrochloride of recipe quantity is dissolved in the purified water of prescription water consumption 25%-30%, it is former to merge each, auxiliary material liquid, continue to stir 3 hours, measure PH, hydrochloric acid solution with 2mol/L is regulated PH to 6.0, according to ambroxol hydrochloride composition freeze-dry orally disintegrating tablet specification, after determining loading amount, the medicinal liquid after merging is pressed in the loading amount packing drug-containing dish, and put into freeze drying box, carry out freezing to medicinal liquid, after ambroxol hydrochloride composition freeze-dry orally disintegrating tablet drying, in freeze drying box, seal cutting after taking out, packing.
Embodiment 3
Preparation ambroxol hydrochloride composition freeze-dry orally disintegrating tablet,
Prescription: 1000 amounts
Preparation technology:
PVP K30 with recipe quantity, polyvinylpolypyrrolidone, lactose, aspartame is dissolved in respectively in the purified water of 10%-15% of prescription water total amount, the gelatin of recipe quantity is joined in the purified water of 10%-15% of prescription water total amount, under stirring, be heated to the boiling dissolving, the ambroxol hydrochloride of recipe quantity is dissolved in the purified water of prescription water consumption 25%-30%, it is former to merge each, auxiliary material liquid, continue to stir 3 hours, measure PH, hydrochloric acid solution with 2mol/L is regulated PH to 6.0, according to ambroxol hydrochloride composition freeze-dry orally disintegrating tablet specification, after determining loading amount, the medicinal liquid after merging is pressed in the loading amount packing drug-containing dish, and put into freeze drying box, carry out freezing to medicinal liquid, after ambroxol hydrochloride composition freeze-dry orally disintegrating tablet drying, in freeze drying box, seal cutting after taking out, packing.
More than show and described ultimate principle of the present invention and principal character and advantage of the present invention.The technical staff of the industry should understand; the present invention is not restricted to the described embodiments; that describes in above-described embodiment and the description just illustrates principle of the present invention; without departing from the spirit and scope of the present invention; the present invention also has various changes and modifications, and these changes and improvements all fall in the claimed scope of the invention.The claimed scope of the present invention is defined by appending claims and equivalent thereof.
Claims (5)
1. ambroxol hydrochloride composition, the prescription of said composition is made of principal agent and accessory drugs, it is characterized in that: wherein principal agent is ambroxol hydrochloride, and accessory drugs includes skeleton agent, forming agent, suspending agent, correctives, disintegrating agent;
Lactose is selected in described skeleton agent, and described forming agent is selected gelatin, and described suspending agent is selected PVP K30, and described correctives is selected aspartame, and described disintegrating agent is selected polyvinylpolypyrrolidone;
Wherein principal agent and accessory drugs by weight the prescription total amount in shared ratio be:
2. a kind of ambroxol hydrochloride composition according to claim 1, it is characterized in that: described compositions preferably includes following composition:
3. ambroxol hydrochloride composition freeze-dry orally disintegrating tablet that contains claim 1 or 2 described ambroxol hydrochloride compositions, it is characterized in that: its composition by following weight ratio is prepared from:
4. a kind of ambroxol hydrochloride composition freeze-dry orally disintegrating tablet according to claim 3 is characterized in that: described ambroxol hydrochloride composition freeze-dry orally disintegrating tablet, and it preferably is prepared from by following composition:
5. the preparation method of an ambroxol hydrochloride composition freeze-dry orally disintegrating tablet claimed in claim 4, it is characterized in that: described preparation method adopts following technical scheme:
A) PVP K30, polyvinylpolypyrrolidone, lactose, the aspartame of recipe quantity is dissolved in respectively in the purified water of 10%-15% of prescription water total amount, the gelatin of recipe quantity is joined in the purified water of 10%-15% of prescription water total amount, under stirring, be heated to the boiling dissolving, the ambroxol hydrochloride of recipe quantity is dissolved in the purified water of prescription water consumption 25%-30%, merge each former, auxiliary material liquid, continue to stir 3 hours, measure PH, regulate PH to 6.0 with the hydrochloric acid solution of 2mol/L;
B) according to ambroxol hydrochloride composition freeze-dry orally disintegrating tablet specification, after determining loading amount, medicinal liquid after merging is moved in the drug-containing dish by loading amount, and put into freeze drying box, and medicinal liquid to be carried out freezing, cryogenic temperature is-20 ℃-50 ℃, evacuation is dry, baking temperature is at+5 ℃-+20 ℃, and vacuum is 0.1 handkerchief-20 handkerchief, and the control moisture is no more than 1.0%;
C) after ambroxol hydrochloride composition freeze-dry orally disintegrating tablet drying, in freeze drying box, seal;
D) will cut drug-containing dish behind the medicament taking-up freeze drying box that freeze, and carry out finished product packing.
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