CN102895207B - Diclofenac sodium sustained-release tablet and preparation method thereof - Google Patents
Diclofenac sodium sustained-release tablet and preparation method thereof Download PDFInfo
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- CN102895207B CN102895207B CN 201210462921 CN201210462921A CN102895207B CN 102895207 B CN102895207 B CN 102895207B CN 201210462921 CN201210462921 CN 201210462921 CN 201210462921 A CN201210462921 A CN 201210462921A CN 102895207 B CN102895207 B CN 102895207B
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Abstract
The invention discloses a diclofenac sodium sustained-release tablet and a preparation method thereof. The diclofenac sodium sustained-release tablet comprises the following raw materials of 50 parts of diclofenac sodium, 36.5-40 parts of Chinese white wax, 8.25-15 parts of microcrystalline cellulose, 15-20 parts of polyvinylpyrrolidone, 11-14 parts of calcium hydrophosphate, 0.8-1 part of magnesium stearate and 1.2-2 parts of talcum powder. The diclofenac sodium sustained-release tablet takes the Chinese white wax as framework, thus being a purely natural product and free from toxic and sideeffects for the human body; the diclofenac sodium sustained-release tablet does not need special technology and adhesive agent, thus being simple in technology and lower in cost; and the diclofenac sodium sustained-release tablet has the characteristics of being hard in sudden release, maintaining the needed blood concentration within a longer time, and being low in collapse release possibility, safe in taking, low in toxic and side effects and high in bioavailability.
Description
Technical field
The invention belongs to the medicament slow release preparation technical field, in particular, is slow releasing tablet of a kind of NSAID (non-steroidal anti-inflammatory drug) diclofenac sodium and preparation method thereof.
Background technology
Inflammation is that body is a kind of immunoreation of sensitinogen to infection or misidentification metabolite, distends the blood vessels, and increases vascular permeability, strengthens the effect of inflammatory mediator Cycloxygenase (COX-2).Arachidonic acid is the precursor of prostaglandin, and the phospholipid that constitutes cell membrane is arachidonic precursor, conversion of arachidonic acid is Cycloxygenase to the prostaglandin conversion, think that at present the epoxidase in the human body has two big classes, epoxidase 1 and epoxidase 2, epoxidase 1 mainly is present in the normal cell, and epoxidase 2 then mainly exists in the inflammatory environment.NSAID (non-steroidal anti-inflammatory drug) can suppress the activeness of Cycloxygenase-2, reduce the synthetic of prostaglandin, alleviate inflammatory reaction, in addition, NSAID (non-steroidal anti-inflammatory drug) can also suppress the activity of phosphodiesterase, can improve the concentration of cAMP in the cell by suppressing phosphodiesterase, reduce lysosomal release thereby stablize lysosome membrane, thus the inflammation-inhibiting reaction.This mechanism of action is with the anti-inflammatory drug glucocorticoid with steroid fundamental difference to be arranged.NSAID (non-steroidal anti-inflammatory drug) is reversible to the inhibitory action of Cycloxygenase; inhibitory reaction is a balancing response; drug effect and blood drug level are closely related; but it is exactly famous aspirin-aspirin that an exception is arranged; the acetyl group of aspirin is ground, coupling collar oxygenase active center serine irreversibly, irreversibly suppresses the epoxidase activity.
The diclofenac sodium chemical name is: 2-(2,6-Dichlorobenzene base) aminophenyl acetic acid sodium.Be a kind of NSAID (non-steroidal anti-inflammatory drug), treatment acute and chronic rheumatic, acute and chronic arthritis, acute and chronic ankylosing spondylitis, osteoarthritis; Scapulohumeral periarthritis, bursitis, tendinitis and tenosynovitis; Lumbago and backache, sprain, strain and other soft tissue injurys etc.Diclofenac sodium acts on and suppresses the Cycloxygenase activity, thereby the blocking-up arachidonic acid is to the conversion of prostaglandin.Simultaneously, it also can promote arachidonic acid to be combined with triglyceride, reduces the arachidonic acid concentration of endocellular liberation, and suppresses the synthetic of leukotriene indirectly; Be that effect is stronger a kind of in the non-steroidal anti-inflammatory medicine, it is better than aspirin and indometacin etc. to the synthetic inhibitory action of prostaglandin.
Diclofenac sodium oral formulations major part is slow releasing tablet at present.The big utility wax class of slow releasing tablet framework material, sodium alginate etc., and how hydroxypropyl emthylcellulose (HPMC), crylic acid resin are as binding agent or filmogen.The skeleton of the Dicolfanac Sodium Sustained Release Tablets of selling on the market mostly is hydroxypropyl emthylcellulose (HPMC) greatly, crylic acid resin, because crylic acid resin is insoluble in water, the preferably adjuvant coupling bigger with HPMC viscosity when being the matrix type slow release with it, consolidate the bonding between each granule, bond effect directly influences the slow release effect of medicine, the complexity of technology when the cost when this has just increased pharmacy and making, adopting the skeleton of the Dicolfanac Sodium Sustained Release Tablets of the present invention's production is that Cera Chinensis is the product of pure natural, to the material of human body without any toxic and side effects, need not use special process and binding agent, technology is simple, and cost is lower.
Summary of the invention
The objective of the invention is to, use a kind of Cera Chinensis of unique natural as sustained-release matrix, this slow releasing tablet blood drug level is steady, effectively reaches antiphlogistic effects.For realizing this purpose, the invention discloses following technology contents:
A kind of NSAID (non-steroidal anti-inflammatory drug) Dicolfanac Sodium Sustained Release Tablets is characterized in that it is made up of following materials based on weight:
50 parts of diclofenac sodiums
Cera Chinensis 36.5-40 part
Microcrystalline Cellulose 8.25-15 part
Polyvinylpyrrolidone 15-20 part
Calcium hydrogen phosphate 11-14 part
Magnesium stearate 0.8-1 part
Pulvis Talci 1.2-2 part.
The preferred NSAID (non-steroidal anti-inflammatory drug) Dicolfanac Sodium Sustained Release Tablets of the present invention is characterized in that it is made up of following materials based on weight:
50 parts of diclofenac sodiums
36.5 parts of Cera Chinensises
8.25 parts of microcrystalline Cellulose
15 parts of polyvinylpyrrolidones
11 parts of calcium hydrogen phosphate
0.8 part of magnesium stearate
1.2 parts of Pulvis Talci.
The present invention further discloses the preparation method of Dicolfanac Sodium Sustained Release Tablets, undertaken by following step:
Supplementary material is sieved respectively; carry out weighing by recipe quantity; with the raw material diclofenac sodium after the weighing and microcrystalline cellulose excipients, polyvinylpyrrolidone, calcium hydrogen phosphate; add and mix abundant mixing in the method granulator; add the skeleton Cera Chinensis of releasing sheet and carry out the high speed granulation, with the wet grain drying that makes, the adding mix lubricant is even; according to the assay tabletting, make Dicolfanac Sodium Sustained Release Tablets.
The slow releasing tablet that contains the diclofenac sodium active component of the present invention is by active component diclofenac sodium and slow-release material, adds other conventional adjuvant composition.The used slow-release material of the present invention is the Cera Chinensis of pure natural, conventional adjuvant is as diluent, binding agent, lubricant etc., concrete composition such as microcrystalline Cellulose, polyvinylpyrrolidone, calcium hydrogen phosphate, magnesium stearate, Pulvis Talci etc., mix with diclofenac sodium, Cera Chinensis by a certain percentage, make slow releasing tablet according to the preparation conventional method.
The main pharmacodynamics research of the Dicolfanac Sodium Sustained Release Tablets (embodiment 1-3) of the present invention's preparation comprises refrigeration function and two tests of pesticide effectiveness of analgesic activity.
Concrete experiment is as follows:
Refrigeration function: three groups of rabbit (n=6), all subcutaneous injection 20% active dry yeast is to cause heating.Then, first group of oral blank (1/, 0); Other two groups respectively the oral enteric sheets (2/only, 50mg) and slow releasing tablet.Record administration (heating moulding) before with administration after the variation of rectal temperature in 10 hours.It is higher more than 1 ℃ than normal body temperature always that blank gives in back 10 hours body temperature; Remarkable cooling effect was arranged after the administration of enteric coatel tablets group in 2-4 hour; Remarkable cooling effect was arranged in 2-9 hour after the administration of slow releasing tablet group, acting duration prolongs more than one times than enteric coatel tablets group.
Analgesic activity: Dicolfanac Sodium Sustained Release Tablets (embodiment 1-3) is ground into behind the fine powder and crude drug all uses 0.5% mucialga of arabic gummy to be made into suspension respectively to 5 and 4 dosage group mouse stomaches (1,2.5,5,10 and 20mg/kg, n=10), give blank solution (0.5% mucialga of arabic gummy) for one group.90 minutes every animal I.P.0.6% acetic acid normal saline 0.2ml record in 15 minutes thereafter and turn round the body number of times after the administration.Calculate ED according to the body percent inhibition of turning round with respect to matched group with the Bliss method
%The ED% of Dicolfanac Sodium Sustained Release Tablets (embodiment 1-3) and crude drug is respectively 1.57 and 2.06mg/kg, and the two no significant difference proves that slow releasing tablet does not reduce analgesia intensity because of component.
Slow releasing tablet of the present invention is compared the distinguishing feature that has with existing slow releasing tablet:
(1) skeleton is all-natural product, and toxic and side effects is little.
(2) do not need to add other binding agent, production cost is low.
(3) technology is simple, and production operation is easy.
Repeatability, the concordance of release rule of the present invention are better, and release is difficult for taking place prominent releasing, and can keep required blood drug level in a long time, it is little to collapse the probability of releasing, and takes safety, and toxic and side effects is little, the bioavailability height, the few characteristics of every day taking dose and number of times.The present invention can adopt first conventional tablet equipment to produce in addition, and production cost is low, and technology is simpler.
Sustained-release tablet recipe screening process of the present invention is as follows:
1. write out a prescription
| Title | Consumption (g) |
| Diclofenac sodium | 50 |
| Cera Chinensis | 36.5 |
| Microcrystalline Cellulose | 8.25 |
| Polyvinylpyrrolidone | 15 |
| |
11 |
| Magnesium stearate | 0.8 |
| Pulvis Talci | 1.2 |
Make 1000.
2. technology:
Supplementary material is sieved respectively, take by weighing former, adjuvant respectively by recipe quantity, fully mixing adds Cera Chinensis and granulates, and dry back adds evenly back tabletting of mix lubricant.
3. prescription screening:
Make 1000
Carry out prescription screening, the result is as follows:
The release in vitro of prescription (1) is when discharging 4 hours, and drug release has reached 90%, does not meet the prescription designing requirement, and is not selected.The release in vitro degree of prescription (2) is discharging 8 hours, and drug release only reaches about 70%, and release profiles is undesirable, does not reach designing requirement.Prescription (3) release in vitro degree approaches the prescription designing requirement, reached 90% in 7 hours in release, but release profiles is undesirable, is not used.Prescription (4) did not also reach 90% in 9 hours at drug release, discharged slowly, did not meet designing requirement.Prescription (5) drug release occurred after 9 hours in 90% o'clock, did not meet designing requirement.90% of prescription (6) drug release also occurred after 9 hours, did not also meet designing requirement.Prescription (7) medicine release in vitro half-life t0.5 is 2 hours, and t0.9 is 8 hours, and medicine release in vitro curve taps into zero level, adheres to specification, and therefore is chosen as standard prescription.The release in vitro of prescription (8) is slightly fast, not selected.
We are according to uniform Design screening prescription (7), and adopt the cross-over experiment method that prescription (7) is carried out the repeatability experiment, and good through 5 * 5 experimental verifications prescription (7) repeatability, the release in vitro degree is zero level, adheres to specification process stabilizing.Tablet appearance meets the requirements, and weight differential meets Chinese Pharmacopoeia (version was two ones in 2010) regulation.Cera Chinensis and ethyl cellulose are the blocker in the slow releasing preparation in the prescription, and ethanol is binding agent, and microcrystalline Cellulose and carboxyl base Starch Sodium are filler and disintegrating agent; Calcium hydrogen phosphate is filler, and is relevant with outward appearance and the mobility of particle of tablet.Magnesium stearate and Pulvis Talci are lubricant.Damp and hot acceleration experiment three months, strong illumination 10 days, tablet appearance, content, dissolution, related substance inspection have no significant change, and have determined that therefore prescription (7) is this product prescription.
The used adjuvant of this product is adjuvant commonly used, and the source is easy, low price, and tablet is simple for process, is fit to suitability for industrialized production, and tablet quality is more stable, and the technology repeatability is good, so this product clinical practice.
4. the mensuration of dissolution curve:
Get three batch samples, 920423(embodiment 1), 920424(embodiment 2), 920425(embodiment 3) measure dissolution respectively, data and dissolution are seen embodiment 1-3.
The adnexa explanation:
Fig. 1 is embodiment 1 Dicolfanac Sodium Sustained Release Tablets stripping curve figure;
Fig. 2 is embodiment 2 Dicolfanac Sodium Sustained Release Tablets stripping curve figure;
Fig. 3 is embodiment 3 Dicolfanac Sodium Sustained Release Tablets stripping curve figure;
Fig. 4 is the Dicolfanac Sodium Sustained Release Tablets stripping curve figure of embodiment comparative experiments.
The specific embodiment
Below in conjunction with embodiment, the present invention is further described, and following embodiment is illustrative, is not determinate, can not limit protection scope of the present invention with following embodiment.
50 parts of diclofenac sodiums
36.5 parts of Cera Chinensises
8.25 parts of microcrystalline Cellulose
15 parts of polyvinylpyrrolidones
11 parts of calcium hydrogen phosphate
0.8 part of magnesium stearate
1.2 parts of Pulvis Talci.
Preparation method: supplementary material is sieved respectively; carry out weighing by recipe quantity; with the raw material diclofenac sodium after the weighing and microcrystalline cellulose excipients, polyvinylpyrrolidone, calcium hydrogen phosphate; add and mix abundant mixing in the method granulator; add the skeleton Cera Chinensis of releasing sheet and carry out the high speed granulation, with the wet grain drying that makes, the adding mix lubricant is even; according to the assay tabletting, make 1000 of Dicolfanac Sodium Sustained Release Tablets.
The preparation technology of embodiment 2-3 is with embodiment 1.
50 parts of diclofenac sodiums
38 parts of Cera Chinensises
8.25 parts of microcrystalline Cellulose
15 parts of polyvinylpyrrolidones
11 parts of calcium hydrogen phosphate
0.8 part of magnesium stearate
1.2 parts of Pulvis Talci.
50 parts of diclofenac sodiums
40 parts of Cera Chinensises
10 parts of microcrystalline Cellulose
15 parts of polyvinylpyrrolidones
11 parts of calcium hydrogen phosphate
0.8 part of magnesium stearate
1.2 parts of Pulvis Talci.
Dissolution data:
Embodiment 4: contrast test
The slow releasing tablet of prior art:
Prescription is formed:
50 parts of diclofenac sodiums
18 parts of hydroxypropyl methylcellulose
22 parts of acrylic resins
15 parts of calcium hydrogen phosphate
1 part of magnesium stearate
1 part of Pulvis Talci
Slow releasing tablet of the present invention:
Prescription is formed:
50 parts of diclofenac sodiums
36.5 parts of Cera Chinensises
8.25 parts of microcrystalline Cellulose
15 parts of polyvinylpyrrolidones
11 parts of calcium hydrogen phosphate
0.8 part of magnesium stearate
1.2 parts of Pulvis Talci.
The result:
| Relatively | Repeatability | Concordance | Prominent releasing | Blood drug level |
| The slow releasing tablet of prior art | Relatively poor | Relatively poor | Relatively poor | Relatively poor |
| Slow releasing tablet of the present invention | Good | Good | Prominent releasing do not discharge more steady | Better |
Existing technology and the present invention all meet release regulation, but existing technology 0-2 hour, 2-6 hour and 6-12 hour burst size be respectively 0%-25%, 25%-55% and the 55%-82% of labelled amount; And the present invention 0-2 hour, 2-6 hour, the burst size of 6-12 hour is respectively labelled amount 0%-35%, 35%-70% and 70%-98%, can find out that in conjunction with figure rate of release of the present invention is faster than existing technology by following table 1, but the two all can reach the purpose of release, as seen from Table 2, the td value of current technology is than big nearly one times of the present invention, and its onset time wants slow relatively.
Table 1: the present invention and existing technology cumulative release percentage rate (n=6)
Table 2:2 kind release in vitro parameter (n=6)
| Sample | t 50(h) | t d(h) | m |
| Existing technology | 5.14±0.23 | 7.79±0.38 | 0.88±0.01 |
| The present invention | 3.04±0.15 | 4.23±0.23 | 1.18±0.19 |
Claims (3)
1. NSAID (non-steroidal anti-inflammatory drug) Dicolfanac Sodium Sustained Release Tablets is characterized in that it is made up of following materials based on weight:
50 parts of diclofenac sodiums
Cera Chinensis 36.5-40 part
Microcrystalline Cellulose 8.25-15 part
Polyvinylpyrrolidone 15-20 part
Calcium hydrogen phosphate 11-14 part
Magnesium stearate 0.8-1 part
Pulvis Talci 1.2-2 part.
2. the described NSAID (non-steroidal anti-inflammatory drug) Dicolfanac Sodium Sustained Release Tablets of claim 1 is characterized in that it is made up of following materials based on weight:
50 parts of diclofenac sodiums
36.5 parts of Cera Chinensises
8.25 parts of microcrystalline Cellulose
15 parts of polyvinylpyrrolidones
11 parts of calcium hydrogen phosphate
0.8 part of magnesium stearate
1.2 parts of Pulvis Talci.
3. the preparation method of claim 1 or 2 described Dicolfanac Sodium Sustained Release Tablets is characterized in that being undertaken by following step:
Supplementary material is sieved respectively; carry out weighing by recipe quantity; with the raw material diclofenac sodium after the weighing and microcrystalline cellulose excipients, polyvinylpyrrolidone, calcium hydrogen phosphate; add and mix abundant mixing in the method granulator; add the skeleton Cera Chinensis of releasing sheet and carry out the high speed granulation, with the wet grain drying that makes, the adding mix lubricant is even; according to the assay tabletting, make Dicolfanac Sodium Sustained Release Tablets.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1771973A (en) * | 2005-10-25 | 2006-05-17 | 张哲峰 | Composite medicine containing nonsteroidal anti-inflammatory analgetic and its prepn |
| CN102048680A (en) * | 2009-11-11 | 2011-05-11 | 河北奥星集团药业有限公司 | Enteric sustained-release preparation containing zaltoprofen and preparation method thereof |
| CN102274200A (en) * | 2011-08-10 | 2011-12-14 | 深圳致君制药有限公司 | Diclofenac sodium sustained release tablets and preparation process thereof |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1771973A (en) * | 2005-10-25 | 2006-05-17 | 张哲峰 | Composite medicine containing nonsteroidal anti-inflammatory analgetic and its prepn |
| CN102048680A (en) * | 2009-11-11 | 2011-05-11 | 河北奥星集团药业有限公司 | Enteric sustained-release preparation containing zaltoprofen and preparation method thereof |
| CN102274200A (en) * | 2011-08-10 | 2011-12-14 | 深圳致君制药有限公司 | Diclofenac sodium sustained release tablets and preparation process thereof |
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Address after: Cheng Lin Zhuang Industrial Zone Tianjin city Dongli District 300163 Patentee after: Xinxin Pharmaceutical Factory of Jinyao Darentang Group Co.,Ltd. Address before: Cheng Lin Zhuang Industrial Zone Tianjin city Dongli District 300163 Patentee before: Zhongxin Pharma Tianjin Xinxin Pharmaceutical Manufactory |