CN102784123A - Diclofenac sodium composition freeze-dried orally disintegrating tablets and preparation method thereof - Google Patents
Diclofenac sodium composition freeze-dried orally disintegrating tablets and preparation method thereof Download PDFInfo
- Publication number
- CN102784123A CN102784123A CN2012103012891A CN201210301289A CN102784123A CN 102784123 A CN102784123 A CN 102784123A CN 2012103012891 A CN2012103012891 A CN 2012103012891A CN 201210301289 A CN201210301289 A CN 201210301289A CN 102784123 A CN102784123 A CN 102784123A
- Authority
- CN
- China
- Prior art keywords
- diclofenac sodium
- oral cavity
- drying
- freeze
- composition freeze
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Abstract
The invention provides diclofenac sodium composition freeze-dried orally disintegrating tablets and a preparation method of the orally disintegrating tablets, relates to the field of a medicine and a medicine preparation method technology and mainly solves the problems in the prior art that the oral diclofenac sodium preparation is poor in curative effect and not suitable for children and the patients who are difficult to swallow. The diclofenac sodium composition freeze-dried orally disintegrating tablets are prepared from the following components by weight: 14-33% of diclofenac sodium, 67-85% of mannitol, 2-4% of gelatin, 0.1-0.15% of trichlorosucrose and 42-67% of tertiary butanol-water. The diclofenac sodium composition freeze-dried orally disintegrating tablets prepared by the above components are easy in preparation process, and simple in components, and mainly meet the administration requirements of children and the patients who are difficult to swallow; moreover, the diclofenac sodium composition freeze-dried orally disintegrating tablets have the advantagesof being fast to disintegrate, convenient to take, and good in taste; and the tablets take effect quickly and are fully absorbed, and the first pass effect of the liver is avoided.
Description
Technical field:
The present invention relates to the method for preparing technical field of medicine and medicine, relate in particular to a kind of diclofenac sodium composition freeze-drying oral cavity disintegration tablet and preparation method thereof.
Background technology:
The diclofenac sodium chemical name is: 2-[(2, the 6-Dichlorobenzene base) amino]-sodium phenylacetate.Molecular formula is C14H10Cl2NNaO2, molecular weight 318.13.Its chemical constitution is:
Diclofenac sodium is a third generation NSAID, is a kind of non-steroidal anti-inflammatory analgesics that is derived from the phenylacetic acid class, and its mechanism of action is active through suppressing Cycloxygenase, thereby the blocking-up arachidonic acid transforms prostaglandin.Simultaneously, it also can promote arachidonic acid to combine with triglyceride (triacylglycerol), reduces the arachidonic acid concentration of endocellular liberation, and suppresses the synthetic of leukotriene indirectly.Play rheumatism, antiinflammatory, pain relieving and refrigeration function.Diclofenac sodium is that effect is stronger a kind of in the non-steroidal antibiotic medicine, and it is better than aspirin and indomethacin etc. to the synthetic inhibitory action of prostaglandin.Compare with other non-steroidal anti-inflammatory drugs and to have stronger antiinflammatory action and higher safety.It has become one of most widely used non-steroidal anti-inflammatory drug in the whole world at present.
Diclofenac sodium biological half-life short (t1/2=1.5hr), enteric coatel tablets need be taken three times every day, and blood concentration fluctuation is big; Oral diclofenac sodium can produce advocates zest, takes for a long time to be prone to cause intestinal mucosa ulcer.
The diclofenac preparation of sodium has dosage forms such as suppository, slow releasing tablet, capsule, gel on the market at present.The patient that regular dosage form such as tablet and capsule etc. are not suitable for child, gerontal patient and dysphagia takes, and makes the patient produce negation to medication, has reduced the compliance of patient's clinical application.
So still lack at present and press for a kind of like this gentamycin sulfate preparation, its preparation technology is simple, component is simple.The oral absorption rate is high, and taking convenience, delicious is specially adapted to child, old age, is unable to leave the bed, the severely-disabled patient, and swallows inconvenient patient's medication.
Summary of the invention:
The object of the invention is to overcome the defective of prior art; When being provided, a kind of taking need not water; Need not to chew, fast diclofenac sodium composition freeze-drying oral cavity disintegration tablet of disintegration rate and preparation method thereof in the oral cavity has improved the dissolution and the bioavailability of diclofenac sodium.This method preparation condition is gentle, is easy to control, is fit to industrialized great production.
For realizing the object of the invention, technical scheme realizes through following mode:
A kind of diclofenac composition of sodium, the prescription of said composition is made up of principal agent and accessory drugs, and wherein principal agent is a diclofenac sodium; Accessory drugs comprises skeleton agent, forming agent, correctives; Mannitol is selected in described skeleton agent for use, and described forming agent is selected gelatin for use, and described correctives is selected sucralose for use.
A kind of diclofenac composition of sodium is characterized in that, said composition comprises following component and component quantity ratio:
Another object of the present invention provides a kind of diclofenac sodium composition freeze-drying oral cavity disintegration tablet that contains above-mentioned diclofenac composition of sodium.This freeze-dry orally disintegrating tablet component is simple, need not water when taking, and need not to chew; Disintegration time was no more than for 2 seconds in human oral cavity, and is rapid-action, the intestinal less residue; Absorb fully, side effect is low, and mouthfeel is good; Be particularly suitable for the infant patient and take, it is characterized in that, be prepared from following component and component quantity ratio:
The preferred ingredient quantity ratio of each component of preparation diclofenac sodium composition freeze-drying oral cavity disintegration tablet is:
A further object of the present invention provides a kind of method for preparing of diclofenac sodium composition freeze-drying oral cavity disintegration tablet; This method for preparing as solvent, can be accelerated the rate of sublimation of medicine with the tertiary butanol and water cosolvent, shortens lyophilization cycle; Increase dissolubility, stability, promote the crystallization of medicine.
For realizing a further object of the present invention, a kind of method for preparing of diclofenac sodium composition freeze-drying oral cavity disintegration tablet adopts following technical scheme:
A) diclofenac sodium with recipe quantity is dissolved in the tert-butyl alcohol of recipe quantity, and stirring and dissolving continues to stir at normal temperatures, preparation solution a;
B) mannitol, the sucralose with recipe quantity is dissolved in the purified water of prescription with pure water total amount 70%-80%, preparation solution b;
C) again the gelatin of recipe quantity and xanthan gum are dissolved in the purified water of prescription water consumption 20%-30%, are heated to dissolving fully, preparation solution c;
D) merge two kinds of solution that above-mentioned steps a, step b obtain and become solution d, and stir, mixed then solution is cooled to below 5 ℃;
E) mix a, two kinds of solution of d, and stir, regulate pH value to 6.0-6.5 with sodium bicarbonate;
F) according to diclofenac sodium composition freeze-drying oral cavity disintegration tablet specification, confirm loading amount after, the medicinal liquid that merges 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 is dry, and (baking temperature is at 0 ℃-5 ℃; Vacuum-more than the 0.09MPa), control moisture be no more than 1.0%;
G) treat diclofenac sodium composition freeze-drying oral cavity disintegration tablet drying after, in household freezer, seal;
H) cut drug-containing dish after the medicament that freezes is taken out freeze drying box, and carry out finished product packing.
Described diclofenac sodium composition freeze-drying oral cavity disintegration tablet specification is 25mg/ sheet, 50mg/ sheet.
Formulated relevant monitoring method to the disintegration rate of diclofenac sodium composition freeze-drying oral cavity disintegration tablet:
Disintegration
According to inspection technique disintegration (two appendix ⅹ of Chinese Pharmacopoeia version in 2010 A); The stainless steel shaft of hanging basket through the upper end hung on the metal rack; Immerse in the 1000ml beaker; And screen cloth fills temperature and is 37 ℃ ± 1 ℃ water apart from beaker bottom 25mm in the beaker when regulating the hanging basket position it being descended, when regulating height of water level hanging basket being risen screen cloth in the underwater 15mm place.
Except as otherwise herein provided, get 6 groups of test samples (every group of dosage is 50mg), put respectively in the glass tubing of above-mentioned 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, the disintegration time and the medicine of different diclofenac sodium tablets reach peak concentration
The disintegration rate that can find out diclofenac sodium composition freeze-drying oral cavity disintegration tablet of the present invention from above experimental result is faster than diclofenac sodium ordinary tablet.
Diclofenac sodium composition freeze-drying oral cavity disintegration tablet in the oral cavity, run into after the saliva can be in two seconds rapidly disintegrate, no grittiness, good mouthfeel, swallow easily, to the oral mucosa nonirritant.
The selected adjuvant of diclofenac sodium composition freeze-drying oral cavity disintegration tablet all is adjuvants of suitable this tablet of preparation; Because the water solublity of diclofenac sodium is very poor, we adopt the tertiary butanol and water cosolvent as solvent in technology, are insoluble in the diclofenac sodium of water with tert-butyl alcohol dissolving; With other adjuvants of purified water dissolving; Both mix with suitable ratio then, are dissolved the clear and bright cosolvent of water solublity and liposoluble substance jointly, use this technology to have multiple advantage.
The first, tert-butyl alcohol freezing point is high, just can freeze at normal temperatures, with also passable after water mixes, just can solidify in the subzero several years; And tert-butyl alcohol vapour pressure is high, helps distillation, so use the tertiary butanol and water cosolvent can shorten freeze-drying time as solvent, the obtained freeze-drying product still keeps porous simultaneously.
The second, the tert-butyl alcohol and water can be with any mixed, and the medicine that will be insoluble in water like this is dissolved in the tert-butyl alcohol, can strengthen stability of drug.
The 3rd, the crystalline state that adds affiliation change water of the tert-butyl alcohol, and then the drug crystallization state that is dissolved in the water is changed, and improving freezing point, rate of sublimation improves greatly.
The 4th, tert-butyl alcohol toxicity is low, and less residue after the lyophilizing, and this just guarantees the safety of medication.
Because diclofenac sodium composition freeze-drying oral cavity disintegration tablet of the present invention is main in order to satisfy child's medication demand, in prescription, has added the correctives sucralose.In traditional production application, aspartame flavour mouthfeel is pretty good, but is prone to decompose instability; Cyclamate, glucide safety receive dispute to a certain degree, and are prone to produce the back bitterness.And the sucralose sweet feel is very near sucrose, and is very stable, safe to heat, acid, alkali.Simultaneously, sucralose is not utilized by the dental caries pathogenic bacteria, can reduce pathogenic bacteria in the oral cavity, and the acid amount of generation and streptococcus cell effectively play the dental caries effect in the adhesion of dental surface, and useful especially teenager teeth is healthy; The sucralose good stability can long term storage, and in freezing dry process, can not be damaged, and is fit to industrial applications.
Advantage of the present invention:
The first, the tablet disintegrate is rapid, and drug effect is fast.Diclofenac sodium composition freeze-drying oral cavity disintegration tablet of the present invention is disintegrate rapidly in 2 seconds in mouth, is beneficial to the rapid stripping of medicine, shortens dissolution time, accelerates to absorb, and liver first-pass effect is little, makes its performance curative effect fast.
The second, drug absorption is abundant.Diclofenac sodium composition freeze-drying oral cavity disintegration tablet of the present invention is disintegrate fully in the oral cavity, makes the absorption of medicine more abundant, helps improving bioavailability of medicament like this.
Three, taking convenience, mouthfeel is good.Diclofenac sodium composition freeze-drying oral cavity disintegration tablet of the present invention needn't be used water delivery service, and saliva can make its complete disintegrate, and no foreign body sensation in mouthful is owing to wherein add the compliance that the sweet child of helping of suitable correctives cool taste flavor takes medicine.Compare with liquid preparation and dosage advantage accurately arranged.
Four, avoid the first pass effect of liver: because diclofenac sodium composition freeze-drying oral cavity disintegration tablet of the present invention rapidly disintegrate in mouth except that major part gets into the gastrointestinal tract with swallowing act, also has the considerable part trans-oral to absorb, thereby rapid-action, first pass effect is little.
The specific embodiment:
For technological means, creation characteristic that the present invention is realized, reach purpose and effect and be easy to understand and understand, below in conjunction with specific embodiment, further set forth the present invention.
Embodiment 1
With the 25mg/ sheet is that example prepares diclofenac sodium composition freeze-drying oral cavity disintegration tablet,
Prescription: 1000 amounts
The diclofenac sodium of recipe quantity is dissolved in the tert-butyl alcohol (among the solution a) of recipe quantity, and stirring and dissolving continues to stir at normal temperatures, and mannitol, the sucralose of recipe quantity is dissolved in the purified water (solution b) of prescription with purified water total amount 70%-80%; Gelatin with recipe quantity is dissolved in the purified water (solution c) of prescription water consumption 20%-30% again, is heated to dissolving fully; Merge above-mentioned b, two kinds of solution of c are solution d, and stir, mixed then solution is cooled to below 5 ℃.Mix a, two kinds of solution of d, and stir, regulate pH to 6.5-7.5 with sodium bicarbonate; According to diclofenac sodium composition freeze-drying oral cavity disintegration tablet specification, confirm loading amount after, with the medicinal liquid after merging by in the loading amount packing drug-containing dish; And put into freeze drying box, medicinal liquid is carried out freezing, treat diclofenac sodium composition freeze-drying oral cavity disintegration tablet drying after; In freeze drying box, seal, take out back cutting, packing.
Embodiment 2
With the 25mg/ sheet is that example prepares diclofenac sodium composition freeze-drying oral cavity disintegration tablet,
Prescription: 1000 amounts
The diclofenac sodium of recipe quantity is dissolved in the tert-butyl alcohol (among the solution a) of recipe quantity, and stirring and dissolving continues to stir at normal temperatures, and mannitol, the sucralose of recipe quantity is dissolved in the purified water (solution b) of prescription with purified water total amount 70%-80%; Gelatin with recipe quantity is dissolved in the purified water (solution c) of prescription water consumption 20%-30% again, is heated to dissolving fully; Merge above-mentioned b, two kinds of solution of c are solution d, and stir, mixed then solution is cooled to below 5 ℃.Mix a, two kinds of solution of d, and stir, regulate pH to 6.5-7.5 with sodium bicarbonate; According to diclofenac sodium composition freeze-drying oral cavity disintegration tablet specification, confirm loading amount after, with the medicinal liquid after merging by in the loading amount packing drug-containing dish; And put into freeze drying box, medicinal liquid is carried out freezing, treat diclofenac sodium composition freeze-drying oral cavity disintegration tablet drying after; In freeze drying box, seal, take out back cutting, packing.
Embodiment 3
Prescription: 1000 amounts
The diclofenac sodium of recipe quantity is dissolved in the tert-butyl alcohol (among the solution a) of recipe quantity, and stirring and dissolving continues to stir at normal temperatures, and mannitol, the sucralose of recipe quantity is dissolved in the purified water (solution b) of prescription with purified water total amount 70%-80%; Gelatin with recipe quantity is dissolved in the purified water (solution c) of prescription water consumption 20%-30% again, is heated to dissolving fully; Merge above-mentioned b, two kinds of solution of c are solution d, and stir, mixed then solution is cooled to below 5 ℃.Mix a, two kinds of solution of d, and stir, regulate pH to 6.5-7.5 with sodium bicarbonate; According to diclofenac sodium composition freeze-drying oral cavity disintegration tablet specification, confirm loading amount after, with the medicinal liquid after merging by in the loading amount packing drug-containing dish; And put into freeze drying box, medicinal liquid is carried out freezing, treat diclofenac sodium composition freeze-drying oral cavity disintegration tablet drying after; In freeze drying box, seal, take out back cutting, packing.
More than show and described ultimate principle of the present invention, 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 the foregoing description and the description is merely preference of the present invention, is not used for limiting the present invention, under the prerequisite that does not break away from spirit and scope of the invention; The present invention also has various changes and modifications, and these variations and improvement all fall in the scope of the invention that requires protection.The present invention requires protection domain to be defined by appending claims and equivalent thereof.
Claims (6)
1. a diclofenac composition of sodium is characterized in that, said composition comprises following component and component quantity ratio:
2. diclofenac composition of sodium according to claim 1 is characterized in that, the preferred ingredient quantity ratio of said each component of diclofenac composition of sodium is:
3. a diclofenac sodium composition freeze-drying oral cavity disintegration tablet that contains the said compositions of claim 1 is characterized in that, is prepared from following component and component quantity ratio:
4. diclofenac sodium composition freeze-drying oral cavity disintegration tablet according to claim 3 is characterized in that, the preferred ingredient quantity ratio of each component of preparation diclofenac sodium composition freeze-drying oral cavity disintegration tablet is:
5. the method for preparing of the said diclofenac sodium composition freeze-drying of claim 3 oral cavity disintegration tablet is characterized in that the concrete steps of this method for preparing are:
A) diclofenac sodium with recipe quantity is dissolved in the tert-butyl alcohol of recipe quantity, and stirring and dissolving continues to stir at normal temperatures, preparation solution a;
B) mannitol, the sucralose with recipe quantity is dissolved in the purified water of prescription with pure water total amount 70%-80%, preparation solution b;
C) again the gelatin of recipe quantity and xanthan gum are dissolved in the purified water of prescription water consumption 20%-30%, are heated to dissolving fully, preparation solution c;
D) merge two kinds of solution that above-mentioned steps a, step b obtain and become solution d, and stir, mixed then solution is cooled to below 5 ℃;
E) mix a, two kinds of solution of d, and stir, regulate pH value to 6.0-6.5 with sodium bicarbonate;
F) according to diclofenac sodium composition freeze-drying oral cavity disintegration tablet specification, confirm loading amount after, the medicinal liquid that merges is moved in the drug-containing dish by loading amount, and puts into freeze drying box, to medicinal liquid carry out freezing, evacuation is dry, the control moisture is no more than 1.0%;
G) treat diclofenac sodium composition freeze-drying oral cavity disintegration tablet drying after, in household freezer, seal;
H) cut drug-containing dish after the medicament that freezes is taken out freeze drying box, and carry out finished product packing.
6. the method for preparing of diclofenac sodium composition freeze-drying oral cavity disintegration tablet according to claim 5 is characterized in that: said diclofenac sodium composition freeze-drying oral cavity disintegration tablet specification is 25mg/ sheet, 50mg/ sheet.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012103012891A CN102784123A (en) | 2012-08-23 | 2012-08-23 | Diclofenac sodium composition freeze-dried orally disintegrating tablets and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012103012891A CN102784123A (en) | 2012-08-23 | 2012-08-23 | Diclofenac sodium composition freeze-dried orally disintegrating tablets and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102784123A true CN102784123A (en) | 2012-11-21 |
Family
ID=47149845
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012103012891A Pending CN102784123A (en) | 2012-08-23 | 2012-08-23 | Diclofenac sodium composition freeze-dried orally disintegrating tablets and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102784123A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1419909A (en) * | 2002-12-19 | 2003-05-28 | 王登之 | Oral cavity disintegrating tablet of diclofenac for treating inflammation and pain, and preparing method thereof |
| CN1689649A (en) * | 2004-04-30 | 2005-11-02 | 量子高科（北京）研究院有限公司 | Oral cavity quick dissolving preparation and production method thereof |
| CN102579376A (en) * | 2011-01-14 | 2012-07-18 | 量子高科（北京）研究院有限公司 | Non-steroidal anti-inflammatory drug orally disintegrating tablet and producing method thereof |
| CN102579378A (en) * | 2012-02-07 | 2012-07-18 | 海南卫康制药(潜山)有限公司 | Child cefdinir composition freeze-dried oral disintegrating tablet and preparation method thereof |
-
2012
- 2012-08-23 CN CN2012103012891A patent/CN102784123A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1419909A (en) * | 2002-12-19 | 2003-05-28 | 王登之 | Oral cavity disintegrating tablet of diclofenac for treating inflammation and pain, and preparing method thereof |
| CN1689649A (en) * | 2004-04-30 | 2005-11-02 | 量子高科（北京）研究院有限公司 | Oral cavity quick dissolving preparation and production method thereof |
| CN102579376A (en) * | 2011-01-14 | 2012-07-18 | 量子高科（北京）研究院有限公司 | Non-steroidal anti-inflammatory drug orally disintegrating tablet and producing method thereof |
| CN102579378A (en) * | 2012-02-07 | 2012-07-18 | 海南卫康制药(潜山)有限公司 | Child cefdinir composition freeze-dried oral disintegrating tablet and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102579378B (en) | Child cefdinir composition freeze-dried oral disintegrating tablet and preparation method thereof | |
| CN102631336B (en) | Freeze-drying orally disintegrating tablet with vitamin K1 composition for infants and preparation method for freeze-drying orally disintegrating tablet | |
| CN102525978B (en) | Children amoxicillin-potassium clavulanate composition | |
| CN102600119B (en) | Pediatric acetaminophen composition | |
| CN102525979B (en) | Infant ibuprofen composition | |
| CN102772383A (en) | Azithromycin composition freeze-dried orally disintegrating tablet and preparation method thereof | |
| CN105193747A (en) | Freeze-dried oral preparation containing agomelatine and preparation method thereof | |
| CN102784119A (en) | Roxithromycin composition freeze-dried orally disintegrating tablets and preparation method thereof | |
| CN104780907A (en) | Medicinal lozenge based on ibuprofen sodium dihydrate | |
| CN102525980B (en) | Children cetirizine hydrochloride composition | |
| CN102784123A (en) | Diclofenac sodium composition freeze-dried orally disintegrating tablets and preparation method thereof | |
| CN102614212B (en) | Freeze-dried orally disintegrating tablets of pediatric ribavirin composition, and preparation method thereof | |
| CN102940610A (en) | Vitamin B6 composition freeze-drying orally disintegrating tablets and preparation method thereof | |
| CN102648899B (en) | Child cefalexin composition | |
| CN104490925A (en) | Vitamin D calcium composition chewable tablets and preparation method thereof | |
| CN102600153B (en) | Pediatric compound anisodamine hydrobromide and chlorpheniramine maleate freeze-dried orally disintegrating tablets and manufacturing method thereof | |
| CN103860517A (en) | Ornithine aspartate effervescent tablets and preparing process thereof | |
| CN102784124A (en) | Cefuroxime axetil composition freeze-dried orally disintegrating tablets and preparation method thereof | |
| CN105250227A (en) | Citric acid caffeine freeze-dried powder and preparation method thereof | |
| CN102784121A (en) | Levofloxacin composition freeze-dried orally disintegrating tablets and preparation method thereof | |
| CN103239478A (en) | Calcium carbonate milk composition freeze-dried orally disintegrating tablets, and preparation method thereof | |
| CN102784122A (en) | Isoniazid composition freeze-dried orally disintegrating tablet and preparation method thereof | |
| CN102784118A (en) | Fosfomycin calcium composition freeze-dried orally disintegrating tablets and preparation method thereof | |
| CN102784117A (en) | Gentamicin sulfate composition freeze-dried orally disintegrating tablet and preparation method thereof | |
| CN102784125A (en) | Cefetamet pivoxil composition freeze-dried orally disintegrating tablet and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20121121 |