CN102266292B - Matrix diclofenac potassium sustained-release pellet capsules and production process thereof - Google Patents
Matrix diclofenac potassium sustained-release pellet capsules and production process thereof Download PDFInfo
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Abstract
The invention relates to matrix diclofenac potassium sustained-release pellet capsules and a production process thereof. The matrix diclofenac potassium sustained-release pellet capsules are prepared by filling matrix diclofenac potassium sustained-release pellets into gastric-soluble capsule shells. The matrix diclofenac potassium sustained-release pellets are prepared in one step by extrusion and rolling. The formula of the matrix diclofenac potassium sustained-release pellets comprises basic remedy diclofenac potassium 10-50%, matrix agent 1-20%, diluent 20-80%, antioxidant 0.1-5%, antisticking agent 0.1-5%, absorption promoting agent 1-10%, and any available wetting agent as balance, wherein the matrix agent is hydrophilic gel matrix agent, or hydrophilic gel matrix agent and erodible matrix agent, or hydrophilic gel matrix agent and insoluble matrix agent. The matrix diclofenac potassium sustained-release pellet capsules provided by the invention have the advantages of high bioavailability, long in vivo holdup time, regular drug release, good in vivo (Beagle dogs) absorption and reproducibility, good sustained-release effect, simple production process, short production period, and no flying of dust during production, and are suitable for industrial production.
Description
Technical field
The invention belongs to medical technical field, relate to a kind of sustained release pharmaceutical formulation, specifically, relate to a kind of matrix type diclofenac potassium sustained-release pellet capsule and production technology thereof.
Background technology
Diclofenac potassium is the potent anthranilic acid of third generation non-steroidal anti-inflammatory analgesics, and its mechanism of action is active for suppressing Cycloxygenase, thereby the blocking-up arachidonic acid transforms prostaglandin.Simultaneously, it also can promote arachidonic acid and triglyceride (triacylglycerol) combination, reduces the arachidonic acid concentration of endocellular liberation, and indirectly suppresses the synthetic of leukotriene.The peroral dosage form of this medicine of domestic and international market is mainly diclofenac potassium tablet at present, usage and dosage is 100～150mg every day (in diclofenac potassium), divide and take for 2～3 times, the person of being in a bad way can reach 200mg/ days (4 slices/day), every day repeatedly frequently medication brought very large inconvenience to the patient, and blood drug level is not steady, peak valley phenomenon occurs, and the medication of high dose has produced very large toxic and side effects.
The diclofenac potassium sustained-release pellet capsule content is spherical slow-release micro-pill, be day clothes slow releasing agent once, this sustained-release micro-pill capsules is the multielement slow-release system simultaneously, compare with slow releasing tablet (unit medicine-releasing system), the sustained-release micro-pill capsules product has following characteristics: (1) can be distributed in rapidly whole gastrointestinal tract, and absorption is stable and local irritation is little; (2) because the set of site-specific drug delivery mini-pill has consisted of whole dosage form and drug release behavior, so the out of control of individual elements can not cause coming down in torrents of whole dosage, so safety is higher; (3) affected by gastric emptying little for polynary release dosage form, and individual variation is less, stable curative effect.Therefore the oral non_steroidal anti_inflammatory drug field of one safe, effective, low toxicity, taking convenience has been opened up again in the successful development of diclofenac potassium sustained-release pellet capsule.
Extrude spheronization and still be widely regarded as so far comparatively novel, superior micropill technology of preparing, it is compared with traditional coating pan pill, centrifugal granulating pill has the operating time of reduction and cost, flexible operation, but the characteristics such as automation mechanized operation.
Inspection information, pertinent literature seldom, the preparation method Chinese patent of the Piclofenac potassium sustained release capsule patent of at present existing Hainan Baina Pharmaceutical Development Co., Ltd. application and a kind of diclofenac potassium sustained-release pellet capsule of our company's application is disclosed, its application number is respectively 200810134825.7 and 200910100649.X, and publication number is respectively CN 101322695A and CN 101612140A.But the present invention and above-mentioned patent have a great difference, the diclofenac potassium sustained-release pellet of above-mentioned two patent disclosures is film controlling type, the former wraps sustained-release coating layer again for elder generation's lamination on celphere at preparation method, latter's preparation method is extruded spheronization and prepares medicine carrying element ball and wrap sealing coat and sustained-release coating layer again for utilizing first, and the two all controls drug release by the clothing film.The present invention adopts and to extrude spheronization one step preparation matrix type diclofenac potassium sustained-release pellet, and is with short production cycle, cost is low, have higher efficient; Be easy to produce amplification, favorable reproducibility; Avoid dust from flying, more meet the GMP requirement.
Summary of the invention
Task of the present invention provides the matrix type diclofenac potassium sustained-release pellet capsule that absorbs favorable reproducibility in hold time in a kind of bioavailability height, the body length, release rule favorable reproducibility, the body, matrix type diclofenac potassium sustained-release pellet capsule of the present invention has greatly reduced administration number of times and accumulated dose, has reduced toxic and side effects; The present invention also provides the method that one step of spheronization prepares the matrix type diclofenac potassium sustained-release pellet of extruding that adopts, the matrix type diclofenac potassium sustained-release pellet capsule is made by diclofenac potassium and is filled to behind the matrix type slow-release micro-pill in the gastric-dissolved capsule shell and gets, technique of the present invention is simple, with short production cycle, without dust from flying, be easy to produce and amplify, and have good slow release effect.
To achieve these goals, the technical solution used in the present invention comprises:
The invention provides a kind of matrix type diclofenac potassium sustained-release pellet, made by diclofenac potassium, skeleton agent, diluent, antioxidant, antiplastering aid, absorption enhancer and the optional wetting agent that exists, it is characterized in that the percentage ratio that each component accounts for total ball weight is: diclofenac potassium 10% ~ 50%, skeleton agent 1% ~ 20%, diluent 20% ~ 80%, antioxidant 0.1% ~ 5%, antiplastering aid 0.1% ~ 5%, absorption enhancer 1% ~ 10%, surplus are wetting agent;
Wherein said skeleton agent is by the hydrogel matrix agent, or hydrogel matrix agent and/or erodible skeleton agent, or hydrogel matrix agent and/or insoluble skeleton agent composition; Also can be insoluble skeleton agent and erodible skeleton agent;
Wherein said hydrogel matrix agent is carbomer; Described erodible skeleton agent is selected from one or more in Brazil wax, castor oil hydrogenated, stearyl alcohol, stearic acid, Polyethylene Glycol monostearate, Glyceryl Behenate, glyceryl monostearate and the Polyethylene Glycol; Described insoluble skeleton agent is selected from one or more in ethyl cellulose, polyethylene, octadecanol, polypropylene, polysiloxanes, polymethyl methacrylate and the crospolyvinylpyrrolidone.
Framework material in the said ratio not only can delay the release of medicine, also can reduce the density of slow-release micro-pill, prolongs the holdup time of slow-release micro-pill in gastrointestinal tract, thereby improves the bioavailability of medicine.
The percentage ratio that preferred version, hydrogel matrix agent of the present invention account for total ball weight is 1% ~ 15%.
Preferred version, hydrogel matrix agent of the present invention is CARBOPOL 974P preferably, and the percentage ratio that accounts for total ball weight is 2% ~ 15%.
Preferred version, diluent of the present invention is selected from one or more in microcrystalline Cellulose, lactose, calcium hydrogen phosphate, calcium sulfate, corn starch, mannitol and the dextrin, preferably microcrystalline cellulose;
Described antioxidant is selected from one or more in sodium sulfite, sodium sulfite, sodium pyrosulfite, the vitamin E, preferred sodium sulfite;
Described antiplastering aid is selected from one or more in calcium chloride, sodium chloride, potassium chloride, sodium sulfate and the potassium sulfate, preferably calcium chloride;
Described absorption enhancer is selected from one or more in tween, the sodium lauryl sulphate;
Described wetting agent is selected from one or more among ethanol, water, PVP and the HPMC.
Matrix type diclofenac potassium sustained-release pellet of the present invention, wherein the micropill size is preferably 0.5 ~ 2.5mm.
Another task of the present invention provides a kind of matrix type diclofenac potassium sustained-release pellet capsule, it is characterized in that by matrix type diclofenac potassium sustained-release pellet described above load to the gastric-dissolved capsule shell and capsule.Matrix type diclofenac potassium sustained-release pellet capsule of the present invention, its specification can be determined as required.Contain diclofenac potassium 50 ~ 200mg in the preferred every capsules of the present invention, more preferably 75mg.
The present invention also provides a kind of method for preparing described matrix type diclofenac potassium sustained-release pellet capsule, it is characterized in that comprising the steps:
(1) diclofenac potassium, skeleton agent and the mixing diluents with recipe quantity evenly makes solid powder mixture; Antioxidant, antiplastering aid, the absorption enhancer of recipe quantity are dissolved in respectively the certain density solution of preparation in the wetting agent; The mentioned solution gradation is added in the above-mentioned solid powder mixture, be uniformly mixed to form soft material;
(2) soft material is added in the extruder, setpoint frequency is that 10 ~ 100Hz is extruded into bar, and frequency is that 20 ~ 150Hz is round as a ball in spheronizator, and round as a ball 5 ~ 60min gets the matrix type diclofenac potassium sustained-release pellet after the drying;
(3) the matrix type diclofenac potassium sustained-release pellet that step (2) is made is packed in the gastric-dissolved capsule shell, gets the matrix type diclofenac potassium sustained-release pellet capsule.
The method that the present invention is described above, wherein slow-release micro-pill adopts and extrudes the spheronizator preparation.
Active pharmaceutical ingredient of the present invention is diclofenac potassium, according to this diclofenac potassium active pharmaceutical ingredient, study by lot of experiments, found that matrix type diclofenac potassium sustained-release pellet of the present invention forms and technique, and then make the matrix type diclofenac potassium sustained-release pellet capsule, has good preparation stability, good release profiles.Adopt framework material in the proportioning of the present invention, reduced the density of slow-release micro-pill, prolonged the holdup time of slow-release micro-pill in gastrointestinal tract, thereby improved the bioavailability of medicine, can overcome the blood drug level peak valley phenomenon of the rear appearance of taking medicine simultaneously.
The mode of taking of matrix type diclofenac potassium sustained-release pellet capsule of the present invention for once-a-day, one time one, reduced administration number of times; Pharmacokinetics experiment shows in Beagle dog body, can keep for a long time drug effect concentration, keeps balance, lasting effective blood drug concentration in equal dosage and interval, thereby increases curative effect, has reached long-acting purpose; Or reduce dosage when keeping equal drug effect, thereby reduce the side effect that drug administration brings to the patient.
The present invention adopts and extrudes spheronization one step preparation matrix type diclofenac potassium sustained-release pellet, and output is high, and technological operation is simple, favorable reproducibility, and without dust from flying, in time, be easy to together produce amplify.
Description of drawings
Fig. 1 is that Beagle dog single oral dose 150mg(is in diclofenac potassium) diclofenac potassium sustained-release pellet capsule of the present invention and 150mg(be in diclofenac sodium) blood drug level-time graph of commercially available Dicolfanac Sodium Sustained Release Tablets (diclofenac).
Specific embodiments
The following examples are used for further specifying and describe the present invention, but and do not mean that the present invention only limits to this.Value is the arbitrary concrete numerical value of scope of the present invention among the embodiment, is and can implements.The preparation method of embodiment 3-7 with embodiment 1 or 2, is omitted.
Embodiment 1 produces 1000 of diclofenac potassium sustained-release pellet capsules of matrix type (in diclofenac potassium 75mg/ grain), and used crude drug, adjuvant and weight proportion thereof are:
Diclofenac potassium 75g
CARBOPOL 974P 12g
Microcrystalline Cellulose 192g
Sodium sulfite 3g
Calcium chloride 3g
Tween 80 15g
Its preparation method is as follows:
(1) principal agent diclofenac potassium 75g, hydrogel matrix agent CARBOPOL 974P 12g and diluents microcrystalline cellulose 192g mix homogeneously are got solid powder mixture; Antioxidant sodium sulfite 3g, antiplastering aid calcium chloride 3g and absorption enhancer tween 80 15g are dissolved in respectively preparation quality volume ratio in the wetting agent water are respectively 6%, 6% and 15% solution; Mentioned solution is added respectively in the above-mentioned solid powder mixture, and stirring makes soft material;
(2) above-mentioned soft material is added in the extruder, setpoint frequency is that 30Hz is extruded into bar, and frequency is that 50Hz is round as a ball in spheronizator, round as a ball 30min, dry (40 ℃, after 12h) the matrix type diclofenac potassium sustained-release pellet;
(3) the matrix type diclofenac potassium sustained-release pellet that step (2) is made is packed in the gastric-dissolved capsule shell, gets 1000 matrix type diclofenac potassium sustained-release pellet capsules, and every contains diclofenac potassium 75mg.Capsule shells of the present invention is the gastric-dissolved capsule shell.
Measure the release of above-mentioned matrix type diclofenac potassium sustained-release pellet capsule with the slurry method, revolution is 100rpm, and take the phosphate buffer of pH6.2 as dissolution medium, water temperature is 37 ℃.After measured, 0.5h stripping 36%, 2h stripping 60%, 8h stripping are more than 80%.
Embodiment 2 produces 1000 of diclofenac potassium sustained-release pellet capsules of matrix type (in diclofenac potassium 75mg/ grain), and used crude drug, adjuvant and weight proportion thereof are:
Diclofenac potassium 75g
CARBOPOL 974P 9g
Microcrystalline Cellulose 180g
Sodium sulfite 3g
Calcium chloride 6g
Tween 80 15g
Its preparation method is as follows:
(1) with principal agent diclofenac potassium 75g, hydrogel matrix agent CARBOPOL 974P 21g and diluents microcrystalline cellulose 180g mix homogeneously; With antioxidant sodium sulfite 3g, antiplastering aid calcium chloride 6g and absorption enhancer tween 80 15g respectively preparation quality volume ratio soluble in water be respectively 6%, 12% and 15% solution; Mentioned solution is added respectively in the above-mentioned solid powder mixture, and stirring makes soft material;
(2) soft material is added in the extruder, setpoint frequency is that 30Hz is extruded into bar, and frequency is that 50Hz is round as a ball in spheronizator, and round as a ball 30min gets the matrix type diclofenac potassium sustained-release pellet after the drying;
(3) the matrix type diclofenac potassium sustained-release pellet that step (2) is made is packed in the gastric-dissolved capsule shell, gets 1000 matrix type diclofenac potassium sustained-release pellet capsules, and every contains diclofenac potassium 75mg.
Measure the release of above-mentioned matrix type diclofenac potassium sustained-release pellet capsule with the slurry method, revolution is 100rpm, and take the phosphate buffer of pH6.2 as dissolution medium, water temperature is 37 ℃.After measured, 0.5h stripping 25%, 2h stripping 47%, 8h stripping are more than 70%.
Embodiment 3 produces 1000 of diclofenac potassium sustained-release pellet capsules of matrix type (in diclofenac potassium 75mg/ grain), and used crude drug, adjuvant and weight proportion thereof are:
Principal agent diclofenac potassium 75g
Hydrogel matrix agent CARBOPOL 974P 9g
Insoluble skeleton agent ethyl cellulose 45g
Diluents microcrystalline cellulose 147g
Antioxidant sodium sulfite 3g
Antiplastering aid calcium chloride 6g
Absorption enhancer Tween 80 15g
Measure the release of above-mentioned matrix type diclofenac potassium sustained-release pellet capsule with the slurry method, revolution is 100rpm, and take the phosphate buffer of pH6.2 as dissolution medium, water temperature is 37 ℃.After measured, 0.5h stripping 32%, 2h stripping 53%, 8h stripping are more than 70%.
Embodiment 4 produces 1000 of diclofenac potassium sustained-release pellet capsules of matrix type (in diclofenac potassium 75mg/ grain), and used crude drug, adjuvant and weight proportion thereof are:
Principal agent diclofenac potassium 75g
Hydrogel matrix agent CARBOPOL 974P 9g
Erodible skeleton agent Glyceryl Behenate 45g
Diluents microcrystalline cellulose 147g
Antioxidant sodium sulfite 3g
Antiplastering aid calcium chloride 6g
Absorption enhancer Tween 80 15g
Measure the release of above-mentioned matrix type diclofenac potassium sustained-release pellet capsule with the slurry method, revolution is 100rpm, and take the phosphate buffer of pH6.2 as dissolution medium, water temperature is 37 ℃.After measured, 0.5h stripping 28%, 2h stripping 51%, 8h stripping are more than 70%.
Principal agent diclofenac potassium 75g
Erodible skeleton agent Glyceryl Behenate 60g
Diluents microcrystalline cellulose 141g
Antioxidant sodium sulfite 3g
Antiplastering aid calcium chloride 6g
Absorption enhancer Tween 80 15g
Measure the release of above-mentioned matrix type diclofenac potassium sustained-release pellet capsule with the slurry method, revolution is 100rpm, and take the phosphate buffer of pH6.2 as dissolution medium, water temperature is 37 ℃.After measured, 0.5h stripping 35%, 2h stripping 59%, 8h stripping are more than 70%.
Embodiment 6 produces 1000 of diclofenac potassium sustained-release pellet capsules of matrix type (in diclofenac potassium 75mg/ grain), and used crude drug, adjuvant and weight proportion thereof are:
Principal agent diclofenac potassium 75g
Insoluble skeleton agent ethyl cellulose 60g
Diluents microcrystalline cellulose 141g
Antioxidant sodium sulfite 3g
Antiplastering aid calcium chloride 6g
Absorption enhancer Tween 80 15g
Measure the release of above-mentioned matrix type diclofenac potassium sustained-release pellet capsule with the slurry method, revolution is 100rpm, and take the phosphate buffer of pH6.2 as dissolution medium, water temperature is 37 ℃.After measured, 0.5h stripping 36%, 2h stripping 62%, 8h stripping are more than 70%.
Embodiment 7 produces 1000 of diclofenac potassium sustained-release pellet capsules of matrix type (in diclofenac potassium 75mg/ grain), and used crude drug, adjuvant and weight proportion thereof are:
Principal agent diclofenac potassium 75g
Insoluble skeleton agent ethyl cellulose 30g
Erodible skeleton agent Glyceryl Behenate 30g
Diluents microcrystalline cellulose 141g
Antioxidant sodium sulfite 3g
Antiplastering aid calcium chloride 6g
Absorption enhancer Tween 80 15g
Measure the release of above-mentioned matrix type diclofenac potassium sustained-release pellet capsule with the slurry method, revolution is 100rpm, and take the phosphate buffer of pH6.2 as dissolution medium, water temperature is 37 ℃.After measured, 0.5h stripping 38%, 2h stripping 60%, 8h stripping are more than 70%.
Embodiment 8 animals (people) pharmacokinetics is measured
Pharmacokinetics test in the Beagle dog body.6 of healthy adult Beagle dogs are divided into first and second liang of groups at random, three every group.
Period 1 first group gives that the present invention makes diclofenac potassium sustained-release pellet capsule (T) by oneself, the second group gives commercially available Dicolfanac Sodium Sustained Release Tablets (diclofenac, R), second round the first group give commercially available Dicolfanac Sodium Sustained Release Tablets (diclofenac, R), the second group gives the present invention and make diclofenac potassium sustained-release pellet capsule (T) by oneself.Two all one weeks of period interval.
Route of administration is single oral dose, and dosage is: the present invention makes diclofenac potassium sustained-release pellet capsule (T) by oneself and is 150mg (in diclofenac potassium), commercially available Dicolfanac Sodium Sustained Release Tablets (diclofenac is that 150mg(is in diclofenac sodium R)).
Beagle dog overnight fasting before the administration, administration gives 50ml water simultaneously.Unified feed standard meal behind the 4h.Administration same day, before taking medicine (0 h) and take medicine after 0.25,0.5,1,1.5,2,3,4,6,8,10,12,14,16,24 h get respectively forearm vein blood 3ml, put in the heparinization test tube, and centrifugal (4000 rpm) 10min draws upper plasma immediately, and-20 ℃ of preservations are to be measured.
Corresponding blood drug level-time graph is seen accompanying drawing 1, the blood drug level measured data see Table 1 with table 2, bioavailability metrics sees Table 3.
Each time blood drug level of Beagle dog (μ g/ml) behind the table 1 single oral dose self-control matrix type diclofenac potassium sustained-release pellet capsule (150mg)
| Time (h) | 1 | 2 | 3 | 4 | 5 | 6 | | SD | |
| 0 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | |
| 0.25 | 6.855 | 4.689 | 4.610 | 1.170 | 33.231 | 0.871 | 8.571 | 12.295 | |
| 0.5 | 27.726 | 2.707 | 6.257 | 6.401 | 47.149 | 1.630 | 15.312 | 18.304 | |
| 1 | 47.133 | 2.334 | 12.001 | 13.552 | 57.834 | 3.312 | 22.694 | 23.749 | |
| 1.5 | 52.500 | 2.898 | 21.392 | 24.915 | 48.441 | 3.101 | 25.541 | 21.378 | |
| 2 | 51.380 | 18.737 | 19.710 | 14.892 | 35.547 | 9.124 | 24.898 | 15.675 | |
| 3 | 16.863 | 14.437 | 9.873 | 15.313 | 33.176 | 22.424 | 18.681 | 8.177 | |
| 4 | 19.315 | 18.553 | 7.066 | 9.004 | 26.165 | 24.975 | 17.513 | 7.955 | |
| 6 | 15.354 | 4.194 | 8.842 | 3.213 | 7.163 | 11.710 | 8.413 | 4.596 | |
| 8 | 15.600 | 3.511 | 1.087 | 5.698 | 4.183 | 26.177 | 9.376 | 9.640 | |
| 10 | 3.623 | 5.233 | 1.002 | 5.596 | 1.734 | 5.091 | 3.713 | 1.951 | |
| 12 | 4.901 | 4.983 | 2.197 | 1.804 | 4.288 | 2.939 | 3.519 | 1.391 | |
| 14 | 3.265 | 5.133 | 6.157 | 7.322 | 2.074 | 8.453 | 5.401 | 2.420 | |
| 16 | 2.080 | 5.401 | 2.673 | 12.463 | 2.297 | 4.285 | 4.867 | 3.937 | |
| 24 | 6.460 | 8.910 | 15.884 | 1.116 | 0.878 | 1.443 | 5.782 | 5.949 |
Each time blood drug level of Beagle dog (μ g/ml) behind the table 2 single oral dose diclofenac (150mg)
| Time (h) | 1 | 2 | 3 | 4 | 5 | 6 | | SD | |
| 0 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | |
| 0.25 | 9.171 | 1.313 | 1.724 | 1.855 | 28.088 | 2.031 | 7.364 | 10.583 | |
| 0.5 | 14.311 | 2.869 | 9.808 | 3.413 | 22.724 | 4.482 | 9.601 | 7.801 | |
| 1 | 35.895 | 2.083 | 14.094 | 11.183 | 18.316 | 6.740 | 14.719 | 11.812 | |
| 1.5 | 19.990 | 1.228 | 24.333 | 13.708 | 10.557 | 19.909 | 14.954 | 8.333 | |
| 2 | 18.555 | 8.280 | 43.283 | 10.333 | 12.867 | 33.869 | 21.198 | 14.210 | |
| 3 | 18.081 | 18.588 | 21.137 | 9.900 | 7.810 | 54.377 | 21.649 | 16.870 | |
| 4 | 10.527 | 12.104 | 17.721 | 9.115 | 8.403 | 21.377 | 13.208 | 5.203 | |
| 6 | 9.218 | 6.557 | 7.962 | 10.565 | 12.848 | 16.743 | 10.649 | 3.688 | |
| 8 | 8.322 | 4.634 | 5.137 | 6.228 | 12.371 | 13.327 | 8.337 | 3.730 | |
| 10 | 4.496 | 4.808 | 4.490 | 2.438 | 6.810 | 9.556 | 5.433 | 2.450 | |
| 12 | 4.207 | 3.511 | 4.343 | 2.184 | 3.773 | 11.529 | 4.925 | 3.326 | |
| 14 | 3.270 | 1.645 | 8.727 | 3.400 | 6.349 | 6.999 | 5.065 | 2.701 | |
| 16 | 2.253 | 3.051 | 8.144 | 2.566 | 6.460 | 5.378 | 4.642 | 2.394 | |
| 24 | 1.339 | 1.368 | 1.728 | 5.878 | 2.378 | 3.369 | 2.677 | 1.745 |
The main pharmacokinetic parameters (150mg, n=6) of two kinds of preparations of table 3 statistical moment estimation diclofenac
| No. | C max (μg/ml) | t max (h) | AUC (0→24) (h·μg/ml) |
| The present invention's self-control | 33.6±17.0 | 2.6±2.7 | 203.9±39.9 |
| Diclofenac | 32.3±15.3 | 1.8±1.1 | 180.4±62.8 |
Measured data shows that in animal (people) experiment, the Piclofenac potassium sustained release capsule blood drug level-time graph of the present invention's preparation is similar to commercially available Dicolfanac Sodium Sustained Release Tablets (diclofenac), i.e. the two bioequivalence.
According to preferred embodiment the present invention is described.Should be understood that the description of front and embodiment are just to explanation the present invention.Under prerequisite without departing from the spirit and scope of the present invention, those skilled in the art can design multiple alternative of the present invention and improvement project, all should be understood to be within protection scope of the present invention.
Claims (9)
1. matrix type diclofenac potassium sustained-release pellet, made by diclofenac potassium, skeleton agent, diluent, antioxidant, antiplastering aid, absorption enhancer and the optional wetting agent that exists, it is characterized in that: described slow-release micro-pill size is 0.5 ~ 2.5mm, counts by weight percentage principal agent diclofenac potassium 10% ~ 50%, skeleton agent 1% ~ 20%, diluent 20% ~ 80%, antioxidant 0.1% ~ 5%, antiplastering aid 0.1% ~ 5%, absorption enhancer 1% ~ 10%, surplus are wetting agent; Wherein said skeleton agent is by the hydrogel matrix agent, or hydrogel matrix agent and erodible skeleton agent, or hydrogel matrix agent and insoluble skeleton agent composition; Wherein said hydrogel matrix agent is selected from carbomer; Described erodible skeleton agent is selected from more than one in Brazil wax, castor oil hydrogenated, stearyl alcohol, stearic acid, Polyethylene Glycol monostearate, Glyceryl Behenate, glyceryl monostearate and the Polyethylene Glycol; Described insoluble skeleton agent is selected from more than one in ethyl cellulose, polyethylene, octadecanol, polypropylene, polysiloxanes, polymethyl methacrylate and the crospolyvinylpyrrolidone.
2. matrix type diclofenac potassium sustained-release pellet according to claim 1 is characterized in that described diluent is selected from more than one in microcrystalline Cellulose, lactose, calcium hydrogen phosphate, calcium sulfate, corn starch, mannitol and the dextrin; Described antioxidant is selected from more than one in sodium sulfite, sodium sulfite, sodium pyrosulfite, the vitamin E; Described antiplastering aid is selected from more than one in calcium chloride, sodium chloride, potassium chloride, sodium sulfate and the potassium sulfate; Described absorption enhancer is selected from more than one in tween, the sodium lauryl sulphate; Described wetting agent is selected from ethanol, water.
3. matrix type diclofenac potassium sustained-release pellet according to claim 1 is characterized in that the hydrogel matrix agent is CARBOPOL 974P, and the percentage ratio that accounts for total ball weight is 2% ~ 15%.
4. arbitrary described matrix type diclofenac potassium sustained-release pellet is characterized in that described diluent is microcrystalline Cellulose according to claim 1-2.
5. arbitrary described matrix type diclofenac potassium sustained-release pellet is characterized in that described antioxidant is sodium sulfite according to claim 1-2.
6. arbitrary described matrix type diclofenac potassium sustained-release pellet is characterized in that described antiplastering aid is calcium chloride according to claim 1-2.
7. matrix type diclofenac potassium sustained-release pellet capsule, it is characterized in that by the arbitrary described matrix type diclofenac potassium sustained-release pellet of claim 1-6 be fills up in the gastric-dissolved capsule shell and capsule, contain diclofenac potassium 50 ~ 200mg in every capsules.
8. matrix type diclofenac potassium sustained-release pellet capsule according to claim 7 contains diclofenac potassium 75mg in every capsules.
9. method for preparing claim 7 or 8 described matrix type diclofenac potassium sustained-release pellet capsules, it is characterized in that adopting and extrude the spheronization preparation, comprise the steps: that specifically (1) evenly make solid powder mixture with diclofenac potassium, skeleton agent and the mixing diluents of recipe quantity; Antioxidant, antiplastering aid, the absorption enhancer of recipe quantity are dissolved in respectively the certain density solution of preparation in the wetting agent; The mentioned solution gradation is added in the above-mentioned solid powder mixture, be uniformly mixed to form soft material; (2) soft material is added in the extruder, setpoint frequency is that 10 ~ 100Hz is extruded into bar, and then frequency is that 20 ~ 150Hz is round as a ball in spheronizator, and round as a ball time 5 ~ 60min gets the matrix type diclofenac potassium sustained-release pellet after the drying; (3) the matrix type diclofenac potassium sustained-release pellet that step (2) is made pack in the gastric-dissolved capsule shell and the matrix type diclofenac potassium sustained-release pellet capsule.
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| CN 201110197866 CN102266292B (en) | 2011-07-14 | 2011-07-14 | Matrix diclofenac potassium sustained-release pellet capsules and production process thereof |
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| CN 201110197866 CN102266292B (en) | 2011-07-14 | 2011-07-14 | Matrix diclofenac potassium sustained-release pellet capsules and production process thereof |
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| CN102266292B true CN102266292B (en) | 2013-03-13 |
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| CN102525943B (en) * | 2012-01-05 | 2014-07-16 | 金陵药业股份有限公司 | Micro-pill and preparation method thereof |
| CN106010221A (en) * | 2016-05-20 | 2016-10-12 | 安徽天彩电缆集团有限公司 | Anticorrosive antisticking ointment composition for cables and preparation method thereof |
| CN108578376A (en) * | 2018-07-27 | 2018-09-28 | 广州柏赛罗药业有限公司 | The sustained release pellet composition of performance improvement |
| CN115317464B (en) * | 2022-09-01 | 2023-08-08 | 苏州弘森药业股份有限公司 | Potassium diclofenac microcapsule and preparation method thereof |
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| CN101322695A (en) * | 2008-08-01 | 2008-12-17 | 海南百那医药发展有限公司 | Piclofenac potassium sustained release capsule and preparing technique thereof |
| CN101612140A (en) * | 2009-07-13 | 2009-12-30 | 浙江金华康恩贝生物制药有限公司 | A kind of preparation method of diclofenac potassium sustained-release pellet capsule |
| CN101804030A (en) * | 2009-02-12 | 2010-08-18 | 杭州赛利药物研究所有限公司 | Sodium dichlorophenolate micro-pill pharmaceutical preparation and preparation method thereof |
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| CN101322695A (en) * | 2008-08-01 | 2008-12-17 | 海南百那医药发展有限公司 | Piclofenac potassium sustained release capsule and preparing technique thereof |
| CN101804030A (en) * | 2009-02-12 | 2010-08-18 | 杭州赛利药物研究所有限公司 | Sodium dichlorophenolate micro-pill pharmaceutical preparation and preparation method thereof |
| CN101612140A (en) * | 2009-07-13 | 2009-12-30 | 浙江金华康恩贝生物制药有限公司 | A kind of preparation method of diclofenac potassium sustained-release pellet capsule |
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