CN103800326B - Pantoprazole sodium medicinal composition, pellet containing composition and preparation method of pellet - Google Patents
Pantoprazole sodium medicinal composition, pellet containing composition and preparation method of pellet Download PDFInfo
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- CN103800326B CN103800326B CN201410039676.1A CN201410039676A CN103800326B CN 103800326 B CN103800326 B CN 103800326B CN 201410039676 A CN201410039676 A CN 201410039676A CN 103800326 B CN103800326 B CN 103800326B
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Abstract
The invention provides a stable pantoprazole sodium medicinal composition. The composition comprises the following components in parts by weight: 10 parts of pantoprazole sodium, 0.05-0.6 part of basic amino acid, 0.5-2.0 parts of antioxidant, 0.05-0.6 part of chelating agent, and 1.2-8.0 parts of pH regulating agent. The invention also provides a preparation containing the medicinal composition, a pellet containing the medicinal composition, a preparation containing the pellet and a preparation method of the pellet. According to the medicinal composition, the stability of pantoprazole sodium can be remarkably improved in the preparing process and the storing process.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, be specifically related to a kind of stable Pantoprazole sodium drug composition, the micropill also having said composition and preparation method thereof.
Background technology
Pantoprazole Sodium; chemistry 5-difluoro-methoxy-2-[(3 by name; 4-dimethoxy-2-pyridinyl) methyl] sulfinyl-1H-benzimidazole sodium salt; it is a kind of novel antiulcerative; it directly acts on gastric mucosa parietal cell; thus gastric acid secretion inhibiting, be applicable to treat gastric ulcer, duodenal ulcer etc., be clinically mainly used in occlusive syndrome, thrombophlebitis, capillary hemorrhage etc.
Pantoprazole Sodium has the chemical constitution of sulfinyl benzimidazole, is subject to the impact of the many factors such as high temperature, light, heavy metal ion, oxidisability and reproducibility composition and unstable.Especially, when acid condition, can there is destructive change in the chemical constitution of Pantoprazole Sodium, will occur variable color and polymerism in appearance.
Because the chemical constitution of Pantoprazole Sodium is unstable, usually need adopts various measures when preparing preparation, such as adding antioxidant, chelating agent etc., to improve it in the stability prepared and in storage process.
When adopting conventional fabrication process preparation pantoprazole sodium injection, because the temperature of preparation water for injection and medicinal liquid is higher, process for preparation and the non-nitrogen filled protection of medicinal liquid course of conveying, can cause the content decline 8-10% of Pantoprazole Sodium.By controlling preparation temperature lower than 10 DEG C, process for preparation fills nitrogen and first adds the means such as stabilizing agent, medicament contg can be made to decline and control at 1-2%.Preparation finally need make the powder of injection by lyophilization, to improve its storage stability.
For the oral solid formulation of Pantoprazole Sodium, as tablet, need to be prepared by the method for dry powder direct tabletting; Or adopt dehydrated alcohol preparation binder solution, prepare the wet granular of medicine, through cold drying except desolventizing, make tabletting after dry granule.
In addition, improve pH value or add alkaline conditioner and also contribute to a certain extent improving the preparation stability of Pantoprazole Sodium.In the preparation of Pantoprazole sodium injection, often by the pH regulator of medicinal liquid to 9-10, solid orally ingestible preparation in often add sodium bicarbonate to improve its stability.
From existing preparation, in order to ensure the stability of pantoprazole preparation of sodium, the main means adopted are low-temperature growth, add stabilizing agent, avoid contact wetting and regulate the methods such as pH.Although these methods can solve the stability problem of preparation to a certain extent, preparation condition is harsher, and is not suitable for for some preparations having to pass through heat treatment process, adopts dehydrated alcohol also to there is safety issue aborning as solvent.
Therefore, need a kind of drug regimen composition formula making pantoprazole stable sodium, tolerate heat treatment operation in production process to enable Pantoprazole Sodium and holding structure is stablized in prolonged storage.
Micropill is a kind of dosage form applied in oral solid formulation at present widely, is pellet medicine and adjuvant being made diameter 0.5 ~ 2.5mm.After the form of micropill made by medicine, be pressed into tablet or fill capsule further.Compared with traditional tablet, capsule, micropill has that drug quality concordance is high, body absorption difference is little, be not subject to the advantages such as gastrointestinal factors impact, one of development trend of current oral solid formulation, for some coated preparations, as film-coat, enteric coating etc. are more applicable.
The phenomenons such as at present when preparing Pantoprazole Sodium micropill, although add conventional stabilizing agent and adjuvant, Pantoprazole Sodium is still unstable in production process and storage process, and variable color easily appears in micropill, medicament contg declines and related substance exceeds standard.In addition, in production process, for reducing thermal histories, generally can avoid adopting and extrude-the method with ripe preparation process such as round as a ball, and usually adopt drug powder directly in the mode of celphere surface medicine-feeding, the more difficult control of this preparation technology, obtained ball wicking surface is more coarse, is unfavorable for follow-up coating processing.
Therefore, preparation has the Pantoprazole Sodium micropill of higher stability, all significant to the exploitation of Pantoprazole Sodium oral formulations, production and guarantee drug safety.
Summary of the invention
An object of the present invention is to provide a kind of stable Pantoprazole sodium drug composition, and the chemical constitution of said composition Pantoprazole Sodium in preparation and prolonged storage is more stable.
Two of object of the present invention is to provide a kind of preparation containing above-mentioned Pantoprazole sodium drug composition.
Three of object of the present invention is to provide a kind of stable Pantoprazole Sodium micropill.
Four of object of the present invention is to provide the preparation containing described Pantoprazole Sodium micropill.
Five of object of the present invention is to provide the preparation method of described Pantoprazole Sodium micropill.
Above-mentioned purpose of the present invention is achieved by the following technical solution:
A stable Pantoprazole sodium drug composition, with parts by weight, comprises following component:
Pantoprazole Sodium 10 parts, basic amino acid 0.05-0.6 part, antioxidant 0.5-2.0 part, chelating agen 0.05-0.6 part and pH adjusting agent 1.2-8.0 part.
Preferably, described Pantoprazole sodium drug composition comprises following component:
Pantoprazole Sodium 10 parts, basic amino acid 0.1-0.3 part, antioxidant 0.8-1.6 part, chelating agen 0.1-0.2 part and pH adjusting agent 1.9-6.0 part.
More preferably, described Pantoprazole sodium drug composition comprises following component:
Pantoprazole Sodium 10 parts, basic amino acid 0.1-0.2 part, antioxidant 0.8-0.9 part, chelating agen 0.1 part and pH adjusting agent 1.9-3.4 part.
Described basic amino acid is selected from one or more in lysine, histidine or arginine, is more preferably lysine or histidine.
Inventor is surprised to find under study for action, the medicine of some easy oxidation discolorations is after mixing with aminoacid, its stability can strengthen, oxidation stain phenomenon reduces, this situation is reflected more clearly on this medicine of Pantoprazole Sodium, namely after adding aminoacid, the stability of Pantoprazole Sodium can obviously strengthen, under there is the synergism of the components such as antioxidant, chelating agen, pH adjusting agent at the same time, can effectively avoid Pantoprazole Sodium that the change of chemical constitution occurs in production process and storage process.
Because alkaline environment is more favourable for the stability of Pantoprazole Sodium micropill, the present invention preferably adopts basic amino acid.
Described antioxidant can be used under alkali condition antioxidant in drug of choice field, and such as sodium sulfite or sodium thiosulfate, be more preferably sodium sulfite.
The effect of described chelating agen is the metal ion for complexation trace, improve medicine stability, the pharmaceutically conventional chelating agen with this effect all can use, such as can be selected from disodium edetate, hydroxyethylethylene diamine tri-acetic acid or aminotriacetic acid, be preferably disodium edetate or aminotriacetic acid, be more preferably disodium edetate.
The effect of described pH adjusting agent makes compositions be alkaline environment, strengthens the stability of Pantoprazole Sodium.Preferably, described pH adjusting agent selected from sodium hydroxide, sodium carbonate or sodium bicarbonate, be more preferably sodium carbonate or sodium bicarbonate, be more preferably sodium carbonate.
According to the needs preparing different dosage form, above-mentioned Pantoprazole Sodium Pharmaceutical composition can also comprise other pharmaceutic adjuvants, such as one or more of adding in appropriate filler, disintegrating agent, binding agent, antiplastering aid, lubricant etc. alternative, to make up-to-standard various dosage forms.These materials, due in chemical inertness, can not have an impact to the stability of Pantoprazole Sodium composition in said composition.
Described pharmaceutical composition can be used for making multiple oral dosage form, and therefore, the present invention also provides a kind of preparation, and described preparation contains above-mentioned Pantoprazole sodium drug composition, and described preparation can be tablet, pill, capsule, granule or powder etc.
Because micropill has, drug quality concordance is high, body absorption difference is little, be not subject to the advantages such as gastrointestinal factors impact, and therefore, the present invention also provides a kind of stable Pantoprazole Sodium micropill, containing above-mentioned Pantoprazole sodium drug composition in described micropill.
In one embodiment of the invention, described micropill contains above-mentioned Pantoprazole sodium drug composition, also further containing filler 18-60 part and disintegrating agent 0-7 part.
The effect of described filler is only to provide enough volumes that preparation is shaped, and the pharmaceutic adjuvant with this effect all can be used as described filler.Preferably, described filler is selected from prepares the conventional filler of micropill, as microcrystalline Cellulose, mannitol, starch or sucrose, is more preferably microcrystalline Cellulose and mannitol.
Described disintegrating agent can select conventional medicinal disintegrating agent, such as carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, crospolyvinylpyrrolidone etc., be more preferably carboxymethyl starch sodium, crospolyvinylpyrrolidone, be more preferably crospolyvinylpyrrolidone.
It should be noted that, whether ball core coating all can be described as micropill, is namely called micropill after ball core coating, and the ball core of non-coating itself also can be described as micropill.
In order to prevent the medicine in micropill by the impact of ambient light, moisture and oxygen, described micropill can be surrounded by coating.Preferably, described micropill is surrounded by hypromellose film-coat, coating weight gain 8-24wt%, is 100% calculating with the weight of ball core.
Described micropill can also be become capsule by fill further or be pressed into tablet.Therefore, the present invention also provides a kind of preparation, and described preparation comprises above-mentioned Pantoprazole Sodium micropill, and described preparation is tablet or capsule.
Composition itself due to described micropill makes Pantoprazole Sodium comparison of ingredients wherein stablize, and the preparation method therefore can applying this area routine prepares micropill, such as extrusion-spheronization, celphere medicine-feeding method, centrifugal granulation, fluidized bed granulation etc.
Because extrusion-spheronization has in preparation technology, output is large, speed of production fast, high repeatability and other advantages, and therefore the present invention also provides a kind of preparation method of Pantoprazole Sodium micropill, and described method is extrusion-spheronization.
Preferably, the preparation method of described Pantoprazole Sodium micropill comprises the steps:
Get each component of recipe quantity, mix homogeneously, add suitable quantity of water and prepare soft material, with extrusion spheronization legal system for ball core, if desired to described ball core bag hypromellose film-coat, to obtain final product.
If necessary, described micropill also can be surrounded by enteric coating outside hypromellose film-coat.
The coating solution composition of hypromellose film-coat can be conventional, and those skilled in the art can need flexible according to actual preparation.Such as in one embodiment, the composition of described coating solution can be: hypromellose 3 ~ 6wt%, sodium carbonate 0.2 ~ 1.0wt%, titanium dioxide 0.5 ~ 1.5wt%, Pulvis Talci 0.2 ~ 1.0wt%, and surplus is distilled water.
More preferably, the coating solution of described hypromellose film-coat consists of: hypromellose 4.0wt%, sodium carbonate 0.4wt%, titanium dioxide 0.7wt%, Pulvis Talci 0.4wt%, and surplus is distilled water.
Concrete coating method can adopt the conventional method of this area, such as fluidized bed coating.Therefore, in a preferred embodiment, fluidized-bed coating machine is adopted to carry out coating to ball core, technical parameter in coating process can flexible according to actual needs, and such as, bed temperature is 35 ~ 45 DEG C, temperature of charge 30 ~ 40 DEG C, whiff pressure controls at 0.1 ~ 0.2MPa, and air blast frequency is 25 ~ 35Hz, regulates constant current revolution speed by slow to fast.
More preferably, bed temperature is 40 DEG C, temperature of charge 35 DEG C, and whiff pressure controls at 0.1 ~ 0.12MPa, and air blast frequency is 30Hz, regulates constant current revolution speed by slow to fast.
Compared with prior art, tool of the present invention has the following advantages:
1) with the addition of basic amino acid especially in pharmaceutical composition of the present invention, and by the synergism with antioxidant, chelating agen and pH adjusting agent, the stability of the Pantoprazole Sodium composition in compositions is improved greatly.Wherein, basic amino acid effectively can improve the structural stability of Pantoprazole Sodium, and reduces metachromatism generation; Antioxidant is for reducing the generation of oxidation of drug reaction, and chelating agen, by the metal ion of trace in chelating preparation, prevents metal ion to the catalytic action of oxidation reaction; PH adjusting agent then ensures that the pH environment of compositions is alkaline state, this is because Pantoprazole Sodium is unstable and relatively stable in alkaline environment in acid, said components synergism, significantly can improve the situation that the variable color of Pantoprazole Sodium formulation aesthetics, medicament contg decline and related substance increase.
2) Pantoprazole Sodium combination of Chinese medicine thing stability of the present invention strengthens greatly, conventional method thus can be adopted to carry out preparation, without the need to specific condition or process.The technique that such as Pantoprazole Sodium micropill can adopt fluid bed drying etc. to have heating process is removed desolventizing and carries out coating to micropill, such preparation process does not all make significant difference to the outward appearance of medicine, content and related substance, and gained pellet preparations has good storage stability, pass through accelerated stability test, there is not significant change in the outward appearance of medicine, medicament contg and related substance be equal conformance with standard also.
Accompanying drawing explanation
Fig. 1 is the drug release patterns of enteric coated mini-pill of pantoprazole sodium.
Detailed description of the invention
Below by way of specific embodiment, technical solution of the present invention and effect thereof are described further.Should be appreciated that the embodiment of the present invention only for illustration of content of the present invention, be not limited to protection scope of the present invention.Apply simple modifications that design of the present invention carries out the present invention all in the scope of protection of present invention.
The preparation of embodiment 1 Pantoprazole Sodium micropill
Take raw material by the recipe quantity in table 1, mix homogeneously, add suitable quantity of water and prepare soft material, add in extrusion spheronization machine and prepare ball core, extrude rotating speed 50rpm, round as a ball rotating speed 30rpm also continues 4 ~ 5min, is placed in 40 DEG C and dries 2h, cross 20 ~ 24 mesh sieves, must contain pill core; Gained, containing pill core hypromellose film coating, controls coating weight gain by the consumption of coating material, obtains Pantoprazole Sodium micropill.
Table 1 Pantoprazole Sodium micropill prescription
Table 1 Pantoprazole Sodium micropill prescription (Continued)
From the outward appearance of the Pantoprazole Sodium micropill that different formulations obtains, the micropill that the R13 formula not adding chelating agen disodium edetate, antioxidant sodium sulfite and basic amino acid obtains is blush, illustrates in preparation process unstable.The micropill outward appearance that other formula obtain is qualified.
Medicament contg in embodiment 2 Pantoprazole Sodium micropill and determination of related substances
Adopt high performance liquid chromatography to detect the change of pantoprazole sodium content and its related substances in Pantoprazole Sodium micropill preparation front and back and put procedure, concrete grammar is as follows:
Assay: be filler with octadecylsilane chemically bonded silica; With 0.01mol/L dipotassium hydrogen phosphate solution (by phosphoric acid adjust ph to 7.0)-acetonitrile (65 ︰ 35) for mobile phase; Determined wavelength is 289nm.Number of theoretical plate calculates by pantoprazole peak and is not less than 2500.
The preparation of need testing solution: get Pantoprazole Sodium micropill appropriate, grinds, accurately weighed, adds 0.00lmol/L sodium hydroxide solution-acetonitrile (1 ︰ 1)) solubilize and quantitatively dilution make the solution about containing Pantoprazole Sodium 40 μ g in every 1ml, to obtain final product.
The preparation of reference substance solution: get Pantoprazole Sodium reference substance appropriate, is made into the solution that concentration is 40 μ g/ml with the solubilize of 0.00lmol/L sodium hydroxide solution-acetonitrile (1 ︰ 1), obtains final product.
Measure: measure, by external standard method with calculated by peak area pantoprazole sodium content according to high performance liquid chromatography (2010 editions Chinese Pharmacopoeias, second annex V D).
Related substance detects: be filler with octadecylsilane chemically bonded silica, and mobile phase A is 0.01mol/L dipotassium hydrogen phosphate solution (use phosphoric acid adjust ph to 7.0), and Mobile phase B is acetonitrile, arranges mobile phase carry out gradient elution by table 2; Determined wavelength 289nm, column temperature 40 DEG C.Number of theoretical plate calculates by pantoprazole peak and is not less than 2500.
Table 2 eluent gradient is arranged
| Time (minute) | Mobile phase A (volume %) | Mobile phase B (volume %) |
| 0 | 90 | 10 |
| 30 | 60 | 40 |
| 45 | 15 | 85 |
The preparation of need testing solution: get Pantoprazole Sodium micropill appropriate, grinds, adds 0.001mol/L sodium hydroxide solution-acetonitrile (1 ﹕ 1)) solubilize and solution about containing Pantoprazole Sodium 0.4mg in every lml is made in dilution, as need testing solution.
The preparation of contrast solution: precision measures this need testing solution 1ml, is placed in 100ml measuring bottle, with above-mentioned 0.001mol/L sodium hydroxide solution-acetonitrile (1:1)) solution dilution to scale, shake up, to obtain final product.
Measure: measure according to high performance liquid chromatography (2010 editions Chinese Pharmacopoeias, second annex V D).Calculate each impurity peak area and contrast solution main peak area in the chromatogram of need testing solution, in need testing solution chromatogram, can ignore in any peak being less than contrast solution main peak area 0.05 times, is calculated as follows its related substances.
Content and the related substance of embodiment 3 preparation front and back and placement micropill Chinese medicine after 10 days change
Get pantoprazole sodium raw materials, prepare the Pantoprazole Sodium micropill of latter 0 day by each formula of embodiment 1, and the Pantoprazole Sodium micropill after preparation after placing 10 days at 60 DEG C, observe the outward appearance of medicine respectively, measure the content of medicament contg and related substance, measurement result is in table 3.
Wherein, the assay method of medicament contg and its related substances is with the method in embodiment 2.
Medicament contg in pantoprazole sodium raw materials and its related substances are practical measurement value.
Prepare the medicament contg placed in the Pantoprazole Sodium micropill after 10 days at latter 0 day and 60 DEG C and refer to the medicament contg of practical measurement and the ratio indicating content.
The change of outward appearance, content and related substance before and after the preparation of table 3 Pantoprazole Sodium micropill, after 10 days
From above result, Pantoprazole Sodium is met damp and hot very easily generation and is degraded and variable color, and micropill (R13) the pantoprazole sodium content in preparation process not containing chelating agen, antioxidant and basic amino acid in formula declines obviously, and its related substances increases.
After adding antioxidant and chelating agen (R1 and R3), in micropill preparation process the content of Pantoprazole Sodium and its related substances change not obvious, but place under 60 DEG C of conditions after 10 days, related substance increases, and color changes.
Add further in prescription (R6, R10 and R12) after basic amino acid, medicine stability be improved significantly, place after 10 days under 60 DEG C of conditions, there is not significant change in color, medicament contg is basicly stable, and related substance slightly increases.
The accelerated stability of embodiment 4 Pantoprazole Sodium micropill is investigated
Get the Pantoprazole Sodium micropill of R6 and R10 prescription, fill, in hard capsule, is placed in 40 DEG C, relative humidity (RH) is under 75% condition, investigates the stability of medicine under acceleration environment.Stability result is in table 4.
The accelerated stability of table 4 Pantoprazole Sodium micropill investigates result
From above result, Pantoprazole Sodium micropill prepared by the present invention after accelerated stability test, appearance stablity, medicament contg and its related substances index all meet the regulation of pharmacopeia, there is good stability, under predicting its room temperature placement condition, 2 years can be reached.
The preparation of embodiment 5 enteric coated mini-pill of pantoprazole sodium
Due to Pantoprazole Sodium, structure is very easily destroyed in acid condition, for ensureing that it is efficiently absorbed after oral in vivo, is generally made into enteric coated preparation when preparing oral formulations, to make medicine not discharge in gastric juice, is absorbed in intestinal release.Therefore, the present invention is further to obtained Pantoprazole Sodium micropill enteric-coating layer, and investigate the feasibility that it prepares enteric coated micropill, specific embodiment is as follows:
The preparation of micropill: the raw material of R6 formula in Example 1, adopts the preparation of the method for embodiment 1 to be surrounded by the Pantoprazole Sodium micropill of hypromellose film-coat.
The preparation of enteric coating liquid:
Get 10g plasticizer to add in 333g water and stir 10min, add 333g ethyl acrylate-methacrylic acid (1:1) copolymer coating material
l30D55, adds Pulvis Talci 25g, is uniformly mixed.
Enteric coating coating: get the above-mentioned Pantoprazole Sodium micropill being surrounded by hypromellose film-coat and be placed in fluidized bed coating equipment, bed temperature controls at 30 DEG C, and temperature of charge 25 ~ 27 DEG C, sprays into coating solution, whiff pressure controls at 0.1 ~ 0.2MPa, and air blast frequency is 30Hz.By input reduction of feed volume control coating weight gain, increase weight to 30% time terminate coating, 40 DEG C solidification 2h, sieve, obtain enteric coated mini-pill of pantoprazole sodium.
Gained enteric coated mini-pill of pantoprazole sodium outward appearance is in the sphere of white, rounding, and place after 10 days and accelerated stability is investigated in the experiment of 6 months for 0 day, 60 DEG C after preparation, its outward appearance, medicament contg and its related substances are as shown in table 5.The assay method of its drug content and its related substances is with embodiment 2.
The influence factor of table 5 enteric coated mini-pill of pantoprazole sodium and accelerated stability investigate result
| Time | Outward appearance | Medicament contg (%) | Related substance (wt%) |
| 0 | White | 98.5 | 0.21 |
| Place 10 days for 60 DEG C | White | 98.3 | 0.39 |
| 40 DEG C, 75%RH, 6 months | White | 98.2 | 0.45 |
From above result, enteric coated mini-pill of pantoprazole sodium of the present invention after preparation 0 day, 60 DEG C place after 10 days and after accelerated stability investigates 6 months, appearance stablity, medicament contg and its related substances index all meet the regulation of pharmacopeia, have good stability.
Dissolution Rate Testing is implemented by the following method:
Mensuration precision takes Pantoprazole Sodium (PAZ-Na) reference substance 25mg and is placed in 100ml volumetric flask, with PH6.8 phosphate buffer for medium is to scale, prepares storing solution.Get respectively storing solution 0.5,1,1.5,2ml is dissolved in 25ml volumetric flask, be diluted to scale, preparation concentration is the reference substance solution of 5,10,15,20 μ g/ml.The reference substance solution 5ml getting 15 μ g/ml is dissolved in 10ml volumetric flask, prepares the reference substance solution of 7.5 μ g/ml.Measure the light absorption value of reference substance solution respectively at 289nm place, draw the standard curve of absorbance and drug level.
Recipe quantity blank auxiliary be dissolved in the PH6.8 phosphate buffer of 900ml, with 0.45 μm of membrane filtration, in 200 ~ 600nm wavelength, place carries out UV scanning, and result display adjuvant is at the noiseless absworption peak in 289nm place.
Determined by ultraviolet spectrophotometry vitro cumulative release, the linear relationship of PAZ-Na concentration and absorbance is y=0.0345x+0.0024 (R2=0.9985, x: μ g/ml), and the range of linearity is 5 ~ 20 μ g/ml.
Carry out according to 2010 editions Chinese Pharmacopoeias, two annex Ⅹ C first methods, get enteric coated mini-pill of pantoprazole sodium appropriate, be placed in and turn basket, rotating speed 100rpm, temperature is (37 ± 0.5) DEG C, and the first hydrochloric acid solution being 0.1N with 900ml concentration, for release medium, changes the PBS of PH6.8 into after 2h; Respectively 5,10,20,30,45,60min time sampling (supplementing the fresh medium of equality of temperature same volume) simultaneously.Under λ=288nm wavelength, adopt determined by ultraviolet spectrophotometry light absorption value, substitution standard curve Solving Equations is got it right and is answered drug dissolution and total release percentage.The drug release patterns of enteric coated mini-pill of pantoprazole sodium is shown in Fig. 1.
As seen from Figure 1, adopt the Pantoprazole Sodium micropill of aqueous enteric coating solution coating, in 0.1N hydrochloric acid solution, 2 hours burst sizes are less than 10%, discharge in the PBS of pH6.8 after 2 hours, through 45min, drug-eluting amount is greater than 80%, meets the general provision of enteric coated preparation.
Claims (21)
1. a stable Pantoprazole sodium drug composition, with parts by weight, comprises following component:
Pantoprazole Sodium 10 parts, basic amino acid 0.05-0.6 part, antioxidant 0.5-2.0 part, chelating agen 0.05-0.6 part and pH adjusting agent 1.2-8.0 part.
2. pharmaceutical composition according to claim 1, is characterized in that, with parts by weight, comprises following component:
Pantoprazole Sodium 10 parts, basic amino acid 0.1-0.3 part, antioxidant 0.8-1.6 part, chelating agen 0.1-0.2 part and pH adjusting agent 1.9-6.0 part.
3. pharmaceutical composition according to claim 1 and 2, is characterized in that, described basic amino acid is selected from lysine, histidine or arginine.
4. pharmaceutical composition according to claim 3, is characterized in that, described basic amino acid is lysine or histidine.
5. pharmaceutical composition according to claim 3, is characterized in that, described antioxidant is selected from sodium sulfite or sodium thiosulfate.
6. pharmaceutical composition according to claim 5, is characterized in that, described antioxidant is sodium sulfite.
7. pharmaceutical composition according to claim 5, is characterized in that, described chelating agen is selected from disodium edetate, hydroxyethylethylene diamine tri-acetic acid or aminotriacetic acid.
8. pharmaceutical composition according to claim 7, is characterized in that, described chelating agen is disodium edetate or aminotriacetic acid.
9. pharmaceutical composition according to claim 8, is characterized in that, described chelating agen is disodium edetate.
10. pharmaceutical composition according to claim 7, is characterized in that, described pH adjusting agent is selected from sodium hydroxide, sodium carbonate or sodium bicarbonate.
11. pharmaceutical compositions according to claim 10, is characterized in that, described pH adjusting agent is sodium carbonate or sodium bicarbonate.
12. pharmaceutical compositions according to claim 11, is characterized in that, described pH adjusting agent is sodium carbonate.
13. pharmaceutical compositions according to claim 10, it is characterized in that, described pharmaceutical composition also comprises pharmaceutic adjuvant, described pharmaceutic adjuvant is selected from one or more in filler, disintegrating agent, binding agent, antiplastering aid, lubricant.
14. 1 kinds of preparations, described preparation is containing the pharmaceutical composition described in good grounds any one of claim 1-13, and described preparation is selected from tablet, pill, capsule, granule or powder.
15. 1 kinds of stable Pantoprazole Sodium micropills, described micropill comprises the pharmaceutical composition described in any one of claim 1-12.
16. micropills according to claim 15, is characterized in that, described micropill also comprises filler 18-60 part, disintegrating agent 0-7 part, and described filler is selected from microcrystalline Cellulose, mannitol, starch, sucrose; Described disintegrating agent is selected from carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, crospolyvinylpyrrolidone.
17. micropills according to claim 16, is characterized in that, described filler is microcrystalline Cellulose or mannitol; Described disintegrating agent is selected from carboxymethyl starch sodium, crospolyvinylpyrrolidone.
18. micropills according to claim 17, is characterized in that, described disintegrating agent is crospolyvinylpyrrolidone.
19. micropills according to any one of claim 15-18, it is characterized in that, described micropill is surrounded by film-coat, coating weight gain 8-24wt%, is 100% calculating with the weight of ball core.
20. 1 kinds of preparations, described preparation is containing the micropill described in good grounds any one of claim 15-19, and described preparation is tablet or capsule.
21. 1 kinds of methods preparing Pantoprazole Sodium micropill described in any one of claim 15-19, comprising: each component of getting recipe quantity, mix homogeneously, add suitable quantity of water and prepare soft material, with extrusion spheronization legal system for ball core, if desired to described ball core bag hypromellose film-coat, to obtain final product.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101002939A (en) * | 2007-01-12 | 2007-07-25 | 广东华南药业有限公司 | Medicine composition for treating diseases relating to gastric acid |
| CN101596165A (en) * | 2008-06-04 | 2009-12-09 | 永信药品工业(昆山)有限公司 | Enteric coated mini-pill of pantoprazole sodium |
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2014
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101002939A (en) * | 2007-01-12 | 2007-07-25 | 广东华南药业有限公司 | Medicine composition for treating diseases relating to gastric acid |
| CN101596165A (en) * | 2008-06-04 | 2009-12-09 | 永信药品工业(昆山)有限公司 | Enteric coated mini-pill of pantoprazole sodium |
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