CN101023917A - Technology for preparing medicine and relative oral preparations - Google Patents
Technology for preparing medicine and relative oral preparations Download PDFInfo
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Abstract
The present invention discloses a preparation process of oral preparation for preparing medicine and its related product. It is characterized by that the active component and matrix are heated to form a molten mixed solution state, then cooled and solidified, and further made into the required dosage form. Said invention is applicable to preparation of medicine and health-care food.
Description
[technical field] a kind of to be used to prepare the preparation technology of the oral formulations of medicine and Related product thereof.
[background technology]
The oral formulations that is used for the preparation of medicine and health food of present clinical use has multiple, and commonly used have tablet, capsule, soft capsule, granule, powder, pill, drop pill, oral liquid, syrup, soft extract, a confection etc.Wherein tablet has conventional tablet, slow releasing tablet, controlled release tablet, buccal tablet (to inhale cloud sheet), Zhu and chew sheet, effervescent tablet etc.; Capsule has conventional capsule, slow releasing capsule, controlled release capsule, enteric coated capsule etc.; Pill has honeyed pill, water-honeyed pill, the watered pill, concentrated pill, drop pill etc.After drop pill is meant solid or liquid medicine and suitable substrate heating and melting mixing, medicine dissolution, emulsifying or be suspended in the substrate, splash in the condensed fluid not miscible, that do not act on mutually, because capillary effect makes drop be shrunk to sphere, the preparation of making through cooled and solidified mainly supplies oral application.Because medicine is with superfine microparticulate, and in solution, become colloid to disperse, and become rapid dissolved amorphous mixture, can improve the dissolubility of oral drugs effectively, increase stability of drug, improve bioavailability of medicament simultaneously, be specially adapted to the preparation of some slightly solubilities, water-insoluble and oiliness pharmaceutical preparation.Because Chinese medicine extract is a kind of multi-component mixture, each component has its characteristic separately again so makes dropping pill formulation is a kind of comparatively ideal selection, the dissolving that not only helps lyotrope matter absorbs, the dissolving that also helps indissoluble or water-insoluble materials absorbs, and can increase stability of drug simultaneously.Start from the Rue oil. drop pill of China in 1971 listing, dropping pill formulation really becomes a kind of use that Chinese medicine also is used for chemical synthetic drug preparation pharmaceutical dosage form widely that effectively both had been used for up till now.
Yet, drop pill requires the molten mass of medicine and substrate must have good flowability in the process of the system of dripping, and the flowability of this molten mass not only be decided by used medicine and used substrate kind and characteristic, the more important thing is used medicine and the selected substrate weight ratio when mixing.The weight of general used medicine is that the weight of 1 o'clock substrate blended with it just can obtain good flowability and forming degree more than 1.5, this ratio of some drugs is reached 1: 7-8, therefore its drug loading is subject to significant restrictions, and then can not make dropping pill formulation with the drop pill technology for the medicine that those oral doses are bigger.Simultaneously, drop pill is with behind medicine and the substrate heating and melting mixing, splash in the condensed fluid not miscible, that do not act on mutually, because capillary effect makes drop be shrunk to sphere, the preparation of making through cooled and solidified is difficult to drip and makes big ball, and general ball is heavy many below 100mg, the existing market dropping pill formulation all below 60mg, makes drug loading limited more obvious.Domestic have how tame research institution having carried out effort for many years aspect the preparation large dripping pillar technical study, only has indivedual units to have brought up to 150mg in the ball at present.Therefore the oral dose of many Chinese medicines of usefulness and part chemical synthetic drug, as the factor of considering that simultaneously the drop pill drug loading is limited, even adopt the large dripping pillar of 150mg once also will take more than 20, is difficult for being accepted by the patient in the gram level clinically.Therefore invent a kind of both close with existing dropping pill formulation useful preparation characteristic, the new oral formulations technology that can overcome the defective workmanship of dropping pill formulation again will have important clinical meaning and market prospect.
[summary of the invention]
The purpose of this invention is to provide a kind of preparation technology who is used to prepare the oral formulations of medicine and Related product thereof, in particular for the designed new preparation technology of predicament who is faced on the preparation technology who solves dropping pill formulation.
To achieve these goals, the present invention will be as the medicine of active component and health food and suitable substrate through being heated as the miscible or miscible state of semi-molten of fusion, by cooling it is solidified then, adopt conventional processing technique to make different preparations such as tablet, capsule, granule, powder, pill, controlled release agent again.
Described substrate includes Polyethylene Glycol
(2000,4000,6000,8000,10000,20000), one or more the composition in polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, stearic acid, sodium stearate, glycerin gelatine, glyceryl monostearate, Lac, polyoxyethylene monostearate, polyethers.Substrate is following but be not limitation of the invention for more than one mixture of ingredients exemplify: polyoxyethylene stearate 40 esters: Polyethylene Glycol=1: 1-10; Betacyclodextrin: Polyethylene Glycol=1: 1-10; Poloxamer: Polyethylene Glycol=1: 1-10; Carboxymethyl starch sodium: Polyethylene Glycol=1: 1-10.
According to the preparation requirement, described substrate also can include other suitable additives, comprising:
1, diluent (filler): for example Icing Sugar, gelatin, glycerol, arabic gum, starch, dextrin, lactose, glucose, mannitol, calcium sulfate, calcium hydrogen phosphate, tricalcium phosphate, gelatinized corn starch, syrup, maltose, gelatine size, cellulose, Kaolin, sodium chloride, modified starch (Sta-RX1500), microcrystalline Cellulose etc., wherein Icing Sugar has sucrose, maltose, dextrinose, dextrinose oligosaccharide, panose, cottonseed sugar, stachyose, oligofructose, fructose, inulin, protein sugar, stevioside, xylitol, maltose alcohol, sorbitol;
2, binding agent: for example water, ethanol, starch, gelatin, sucrose, glucose, dextran, syrup, lactose, arabic gum, sodium alginate, gelatine size, polyvinylpyrrolidone, Polyethylene Glycol, methylcellulose, carboxymethyl cellulose, ethyl cellulose, hydroxypropyl cellulose, maltose, sucrose dextrin copolymer;
3, disintegrating agent: for example starch (corn and potato starch), cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, carboxymethyl starch sodium, pectin, carboxymethyl cellulose, microcrystalline Cellulose, tween 80, sodium laurylsulfate, stearyl alcohol sodium sulfonate, kaolin.
4, lubricant: for example stearic acid, calcium stearate, magnesium stearate, zinc stearate, hydrogenated vegetable oil, polyoxyethylene monostearate, light mineral oil, liquid paraffin, boric acid, sodium chloride, sodium benzoate, sodium acetate, enuatrol, sodium laurylsulfate (magnesium), single Laurel sucrose acid ester, adipic acid, fumaric acid, three triacetins, Polyethylene Glycol
1500～20000
5, fluidizer: for example starch, purified talc, differential silica gel, pyrolytic silicon dioxide, hydrated sodium aluminosilicate.
6, slow releasing agent: for example hydroxypropyl cellulose, hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose, carbomer, stearic acid, hexadecanol, octadecanol, Polyethylene Glycol, ethyl cellulose, zein etc.
Thermal recovery water-bath, oil bath, electric heating or other mode of heating of adding of the present invention is heated to fusion with mixed material, stirs, heating-up temperature specifically includes but not limited to 1 greater than 40 ℃) get substrate, be heated to the miscible or miscible state of semi-molten of fusion, add active component then, mixing; 2) get substrate and active component, mixing is heated to the miscible or miscible state of semi-molten of fusion; 3) get active component, be heated to uniform temperature, add substrate then, continue to be heated to the miscible or miscible state of semi-molten of fusion; 4) get substrate, be heated to the miscible or miscible state of semi-molten of fusion, add active component then, mixing continues to be heated to the miscible or miscible state of semi-molten of fusion.
The preparation that the present invention suited includes but not limited to tablet, capsule, granule, powder, pill, controlled release agent, its preparation method can select 1) when medicine and substrate through being heated into molten condition, being cooled to uniform temperature becomes the soft material shape, selects suitable film-making or granulator straight forming then; 2) when medicine and substrate through being heated into molten condition; by cooling it is solidified; select suitable granulator to granulate then; form on request again; through the tablet machine compression molding, capsule is shaped through gained drug particles fill capsule tablet with the gained drug particles, and granule and powder are through directly packing molding; pill adds machine molding on the desired binding agent with the gained drug particles, and controlled release agent can be realized by changing methods such as substrate composition.
A kind of preparation method provided by the present invention is as follows:
With medicine or health food is primary raw material, according to certain ratio, adds substrate such as surfactant polyethylene, is prepared from through specific technology, apparatus processing again.Specific as follows:
(1) prescription: medicine+substrate;
Medicine: be medicine or health food.
Substrate: include Polyethylene Glycol
(2000,4000,6000,8000,10000,20000), in polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, stearic acid, sodium stearate, glycerin gelatine, glyceryl monostearate, Lac, polyoxyethylene monostearate, polyethers one or more composition and other additives.
Medicine: substrate≤1: 0.1, promptly substrate is no less than 10% in total dose;
(2) preparation technology: concrete implementation step is as follows:
The first step is mixed medicine according to certain ratio with matrix phase; Substrate can be Polyethylene Glycol
(2000,4000,6000,8000,10000,20000), any one or a few and other additives in polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, stearic acid, sodium stearate, glycerin gelatine, glyceryl monostearate, Lac, polyoxyethylene monostearate, polyethers etc. mix mutually.
Second step was adopted water-bath, oil bath, electric heating or other mode of heating, and mixed material is heated to fusion, stirred;
The 3rd step cooled and solidified, granulating or being cooled to proper temperature becomes soft material.
The 4th step selected suitable machine to carry out molding.
The pharmaceutical preparation of the employing solid dispersion technology that [beneficial effect] is involved in the present invention; utilize Polyethylene Glycol; polyoxyethylene stearate 40 esters; betacyclodextrin; poloxamer; carboxymethyl starch sodium; substrate such as stearic acid and medicine material are made solid dispersion by heating; make medicine be molecule; colloid or microcrystalline state are scattered in the substrate; the total surface area of medicine increases; and substrate is hydrophilic; medicine had wetting action; can make medicine molten microgranule or the solution of loosing into rapidly; thereby make the dissolving of medicine and absorb quickening; thereby improved bioavailability and stability, performance is efficient; Stabilization etc.The drop pill technology that is adopted in the market also has above-mentioned beneficial effect, but because the drug loading of dropping pill formulation is little, less than 40% of pharmaceutical preparation gross weight, is difficult to make large dripping pillar simultaneously, and generally each ball weight average is below 60mg.The disposable dosage of at present used clinically most of Chinese medicine preparation is more than 0.5g, and the disposable dosage of many chemical synthetic drugs is also more than 0.25g, as select drop pill, one less importantly takes tens even tens, not only the patient is difficult to accept, and also affects the accuracy of dosage simultaneously, therefore, existing drop pill technology is only applicable to the less medicine of dosage, significant limitation the use of this technology in pharmaceuticals industry.The technology of the present invention had both solved the problem of drug loading, can make drug loading bring up to 90% of pharmaceutical preparation gross weight, the weight that makes each medicine does not simultaneously have difference with the weight of existing pharmaceutical preparation, maximum can be made into 1g or the above preparation of 1g, as tablet or capsule, obviously improve the application of this solid dispersion technology in the drug oral preparation, not only had the important clinical meaning, also had good market prospect simultaneously.
Description of drawings
Fig. 1 is the influence of the present invention to the water-insoluble drug stripping property.
Fig. 2 is the influence of the present invention to the poorly water soluble drugs stripping property.
Fig. 3 is the influence of the present invention to slightly soluble drug dissolution in the water.
Fig. 4 A is the experimental result of the present invention to the drug loading of propafenone hydrochloride.
Fig. 4 B is the drug loading experimental result of the present invention to the amoxicillin
Fig. 5 is the experimental result of the capsule formulation stripping property of prepared of the present invention.
Fig. 6 is the influence of the amoxicillin buccal tablet of prepared of the present invention to stripping property.
Fig. 7 is the influence of technology of the present invention to the stability of clavulanate potassium
[specific implementation method]
By following concrete embodiment, can further understand the present invention, but following example not a limitation of the invention.
Embodiment 1-the present invention is to the influence of water-insoluble drug stripping property
Medicine: irbesartan is water-insoluble drug.
Dosage form: tablet
Method:
1, matched group preparation technology: get irbesartan 15 grams, pregelatinized starch 5 grams, micropowder silica gel 6 grams, polyethylene glycol 6000 26 grams, mixing respectively, the 10%PVPk30 wet granulation, 37 ℃ of oven dry, cross 20 mesh sieves, add microcrystalline Cellulose 9 grams, carboxymethyl starch sodium 8.5 grams, magnesium stearate 0.5 gram, fully mix, the heavy 0.35g irbesartan of compacting sheet on tablet machine, every contains 75 milligrams of irbesartans.
2, experimental group preparation technology of the present invention: get irbesartan 15 grams, pregelatinized starch 5 grams, micropowder silica gel 6 grams, polyethylene glycol 6000 26 grams, mixing respectively, adopt electrically heated mode with the supplementary material mixture heated that makes to molten condition, cooled and solidified, granulate, cross 20 mesh sieves, add microcrystalline Cellulose 9 grams, carboxymethyl starch sodium 8.5 grams, magnesium stearate 0.5 gram, fully mix, the heavy 0.35g irbesartan of compacting sheet on tablet machine, every contains 75 milligrams of irbesartans.
The experiment of 0.1M dilute hydrochloric acid dissolution is carried out in sampling respectively.
Result: see Fig. 1, illustrate that technology of the present invention can increase the dissolution of irbesartan in the 0.1M dilute hydrochloric acid.
Embodiment 2-the present invention is to the influence of insoluble drug stripping property
Medicine: propafenone hydrochloride is poorly water soluble drugs.
Dosage form: tablet
Method:
1, matched group preparation technology: get propafenone hydrochloride 15 grams, Macrogol 4000 3 grams, polyethylene glycol 6000 12 grams, mixing respectively, dry granulation, cross 20 mesh sieves, the heavy 0.3g propafenone hydrochloride of compacting sheet on tablet machine, 150 milligrams of every hydrochloric Propafenones.
2, experimental group preparation technology of the present invention: get propafenone hydrochloride 15 grams, Macrogol 4000 3 grams, polyethylene glycol 6000 12 grams, mixing respectively, adopt electrically heated mode with the supplementary material mixture heated that makes to molten condition, cooled and solidified, granulate, cross 20 mesh sieves, the heavy 0.3g propafenone hydrochloride of compacting sheet on tablet machine, 150 milligrams of every hydrochloric Propafenones.
The dissolution experiment is carried out in sampling respectively.
Result: see Fig. 2, illustrate that technology of the present invention can increase the dissolution of poorly water soluble drugs propafenone hydrochloride.
Embodiment 3-the present invention is to the influence of slightly soluble drug dissolution in the water
Medicine: amoxicillin, slightly soluble medicine in the water.
Dosage form: tablet
Method:
1, matched group preparation technology: get amoxicillin 15 grams, Macrogol 4000 3 grams, polyethylene glycol 6000 12 grams, mixing respectively, dry granulation is crossed 20 mesh sieves, the heavy 0.3g of compacting amoxicillin sheet on tablet machine, and every contains 150 milligrams of amoxicillin.
2, experimental group preparation technology of the present invention: get amoxicillin 15 grams, Macrogol 4000 3 grams, polyethylene glycol 6000 12 grams, mixing respectively, adopt electrically heated mode with the supplementary material mixture heated that makes to molten condition, cooled and solidified, granulate, cross 20 mesh sieves, the heavy 0.3g of compacting amoxicillin sheet on tablet machine, every contains 150 milligrams of amoxicillin.
The dissolution experiment is carried out in sampling respectively.
Result: see Fig. 3, illustrate that technology of the present invention can increase the dissolution of slightly soluble medicine amoxicillin in the water.
Embodiment 4-the present invention is to the influence of drug loading
Medicine: slightly soluble medicine amoxicillin, poorly water soluble drugs propafenone hydrochloride in the water
Dosage form: tablet
Method: the proportioning of 6 kinds of different principal agents of experimental selection and adjuvant, promptly 1: 10,1: 2,1: 1.5,1: 1,1: 0.67,1: 0.43,1: 0.25, mainly get 10 grams, polyethylene glycol 6000 as adjuvant is respectively 100,20,15,10,6.7,4.3,2.5 grams, prepare 0.3 grammes per square metre tablet, every content of dispersion is respectively 27,100,120,150,180,210,240 milligrams.
1, amoxicillin matched group preparation technology: various dose, the mixing of getting amoxicillin 10 grams, polyethylene glycol 6000 100 to 2.5 grams respectively, dry granulation, cross 20 mesh sieves, the heavy 0.3g of compacting amoxicillin sheet on tablet machine, the every amoxicillin that contains is respectively 27,100,120,150,180,210,240 milligrams.
2, amoxicillin experimental group preparation technology of the present invention: various dose, the mixing of getting amoxicillin 10 grams, polyethylene glycol 6000 100 to 2.5 grams respectively, adopt electrically heated mode with the supplementary material mixture heated that makes to molten condition, cooled and solidified, granulate, cross 20 mesh sieves, the heavy 0.3g of compacting amoxicillin sheet on tablet machine, the every amoxicillin that contains is respectively 27,100,120,150,180,210,240 milligrams.
3, propafenone hydrochloride matched group preparation technology: various dose, the mixing of getting propafenone hydrochloride 10 grams, polyethylene glycol 6000 100 to 2.5 grams respectively, dry granulation, cross 20 mesh sieves, the heavy 0.3g propafenone hydrochloride of compacting sheet on tablet machine, every hydrochloric Propafenone is respectively 27,100,120,150,180,210,240 milligrams.
4, propafenone hydrochloride experimental group preparation technology of the present invention: various dose, the mixing of getting propafenone hydrochloride 10 grams, polyethylene glycol 6000 100 to 2.5 grams respectively, adopt electrically heated mode with the supplementary material mixture heated that makes to molten condition, cooled and solidified, granulate, cross 20 mesh sieves, the heavy 0.3g propafenone hydrochloride of compacting sheet on tablet machine, every hydrochloric Propafenone is respectively 27,100,120,150,180,210,240 milligrams.
The dissolution experiment is carried out in sampling respectively.Solvent is a water, according to 1 milliliter of consumption that calculates each stripping experiment water of every milligram of medicine water in the tablet to be measured.
The result: Fig. 4 A is the drug loading experimental result of propafenone hydrochloride, from scheming as seen, drug loading is lower than at 70% o'clock, technology of the present invention can increase the dissolution of propafenone hydrochloride, but when reaching 70%, technology of the present invention is compared with matched group, does not then have significant difference, illustrates that technology of the present invention can be increased to 70% with the drug loading of propafenone hydrochloride preparation.
Fig. 4 B is the drug loading experimental result of amoxicillin, from scheming as seen, drug loading is lower than at 70% o'clock, technology of the present invention can increase the dissolution of amoxicillin, but when reaching 70%, technology of the present invention is compared with matched group, does not then have significant difference, illustrates that technology of the present invention can be increased to 70% with the drug loading of Wymox.
Embodiment 5-different heating method is to the influence of drug dissolution
Medicine: propafenone hydrochloride is poorly water soluble drugs.
Dosage form: tablet
Method:
Experiment is divided into heating in water bath group, oil bath heating group, electric baker heating group and electrothermal plate heating group.Propafenone hydrochloride 10 gram, Macrogol 4000 2 grams, polyethylene glycol 6000 8 four parts of grams, mixing and adopt supplementary material mixture heated that heating in water bath, oil bath heating, electric baker heating and electrothermal plate heating will make respectively to molten condition, cooled and solidified, granulate, cross 20 mesh sieves, the heavy 0.3g propafenone hydrochloride of compacting sheet on tablet machine, 150 milligrams of every hydrochloric Propafenones.The dissolution experiment is carried out in sampling respectively.
The result: heating in water bath group, oil bath heating group, electric baker heating group and 30 minutes dissolution rates of electrothermal plate heating group gained preparation are respectively 85%, 85%, 87% and 89%, no significant difference.
The preparation of embodiment 6-technology capsule formulation of the present invention reaches the influence to drug dissolution
Medicine: amoxicillin, slightly soluble medicine in the water.
Dosage form: tablet
Method:
1, matched group preparation technology: get amoxicillin 15 grams, Macrogol 4000 3 grams, polyethylene glycol 6000 12 grams, mixing respectively, dry granulation is crossed 20 mesh sieves, and the fill capsule is made heavy 0.3g Amoxicillin Capsules, and every contains 150 milligrams of amoxicillin.
2, experimental group preparation technology of the present invention: get amoxicillin 15 grams, Macrogol 4000 3 grams, polyethylene glycol 6000 12 grams, mixing respectively, adopt electrically heated mode with the supplementary material mixture heated that makes to molten condition, cooled and solidified, granulate, cross 20 mesh sieves, the fill capsule is made heavy 0.3g Amoxicillin Capsules, and every contains 150 milligrams of amoxicillin.
The dissolution experiment is carried out in sampling respectively.
Result: see Fig. 5, illustrate that technology of the present invention can increase the dissolution of Amoxicillin Capsules.
The preparation of embodiment 7-technology buccal tablet of the present invention dosage form reaches the influence to drug dissolution
Medicine: amoxicillin, slightly soluble medicine in the water.
Dosage form: tablet
Method:
1, matched group preparation technology: get 100 milligrams of amoxicillin 25 grams, polyethylene glycol 6000 35 grams, hydroxypropyl methylcellulose 8 grams, aspartame respectively, mixing, dry granulation is crossed 20 mesh sieves, the heavy 0.681g of compacting amoxicillin buccal tablet on tablet machine, every contains 250 milligrams of amoxicillin.
2, experimental group preparation technology of the present invention: get 100 milligrams of amoxicillin 25 grams, polyethylene glycol 6000 35 grams, hydroxypropyl methylcellulose 8 grams, aspartame respectively, mixing, adopt electrically heated mode with the supplementary material mixture heated that makes to molten condition, cooled and solidified, granulate, cross 20 mesh sieves, the heavy 0.681g of compacting amoxicillin sheet on tablet machine, every contains 250 milligrams of amoxicillin.
The dissolution experiment is carried out in sampling respectively.
Result: see Fig. 6, illustrate that technology of the present invention can increase the dissolution of amoxicillin buccal tablet.
The preparation of embodiment 8-technology concentrated pill of the present invention dosage form
Medicine: Fructus Schisandrae Chinensis concentrated pill.
Dosage form: pill
Method: matched group preparation technology: with the broken kernel of Fructus Schisandrae Chinensis is primary raw material, be impregnated with ethanol, filter, behind the filtrate standing separation oil reservoir, decompression recycling ethanol, concentrate is a Chinese Magnoliavine Fruit alcohol extract, get Chinese Magnoliavine Fruit alcohol extract 30 grams, polyethylene glycol 6000 30 grams, mixing respectively, adopt electrically heated mode with the supplementary material mixture heated that makes to molten condition, cooled and solidified is granulated, cross 20 mesh sieves, adopting general method for making is binding agent with the glutinous paste, makes heavy 0.3 gram Fructus Schisandrae Chinensis concentrated pill, and every ball contains 150 milligrams of Chinese Magnoliavine Fruit alcohol extracts.
Embodiment 9-the present invention is to the influence of medicine stability
Medicine: the mixture of amoxicillin and clavulanate potassium (2: 1).
Dosage form: powder
Method: clavulanate potassium is a kind of unstable in the environment of oxygen is arranged, and is easy to the medicine of oxidized decomposition.Clavulanate potassium after this test will be granulated reacts in the airtight oxygen environment that adopts hydrogen peroxide and a little zinc deblocking reaction to form with the form bulk storage of powder, measure the content of undecomposed clavulanate potassium then with high-pressure liquid phase, calculate the percentage composition of undecomposed clavulanate potassium, to compare the influence of technology of the present invention to clavulanate potassium stability with matched group.
1, matched group preparation technology: mixture 15 grams, Macrogol 4000 3 grams, polyethylene glycol 6000 12 grams, the mixing of getting amoxicillin and clavulanate potassium (2: 1) respectively, dry granulation, cross 20 mesh sieves, make powder, take by weighing 9 parts, 50 milligrams every part, be tiled in diameter and be on 1 centimetre the pan paper, place the airtight oxygen environment that contains hydrogen peroxide and the formation of a little zinc deblocking reaction to react, detect the content of the undecomposed clavulanate potassium of different time.
2, experimental group preparation technology of the present invention: mixture 15 grams, Macrogol 4000 3 grams, polyethylene glycol 6000 12 grams, the mixing of getting amoxicillin and clavulanate potassium (2: 1) respectively, adopt electrically heated mode with the supplementary material mixture heated that makes to molten condition, cooled and solidified, granulate, cross 20 mesh sieves, make powder, take by weighing 9 parts, 50 milligrams every part, be tiled in diameter and be on 1 centimetre the pan paper, place the airtight oxygen environment that contains hydrogen peroxide and the formation of a little zinc deblocking reaction to react, detect the content of the undecomposed clavulanate potassium of different time.
Result: see Fig. 7, illustrate that technology of the present invention can increase the stability of clavulanate potassium.
Claims (8)
1. preparation technology who is used to prepare the oral formulations of medicine and Related product thereof, it is characterized in that described preparation technology is through being heated as the miscible or miscible state of semi-molten of fusion by active component and substrate, then through cooled and solidified, and then make required dosage form and form.
2. preparation technology according to claim 1 is characterized in that: described active component comprises medicine and health food.
3. preparation technology according to claim 1 is characterized in that: described substrate includes one or more the composition in Polyethylene Glycol (2000,4000,6000,8000,10000,20000), polyoxyethylene stearate 40 esters, betacyclodextrin, poloxamer, carboxymethyl starch sodium, stearic acid, sodium stearate, glycerin gelatine, glyceryl monostearate, Lac, polyoxyethylene monostearate, the polyethers.
4, preparation technology according to claim 1 is applicable to but is not limited to the preparation of tablet, capsule, granule, powder, pill, controlled release agent.
5. adopting preparation technology of the present invention to prepare the described various preparations of claim 4 is through being heated as the miscible or miscible state of semi-molten of fusion with the described active component of claim 2 and the described substrate of claim 3, by cooling it is solidified then, adopt conventional processing technique to make again.
6, heating means according to claim 5 include but not limited to 1) get substrate, be heated to the miscible or miscible state of semi-molten of fusion, add active component then, mixing; 2) get substrate and active component, mixing is heated to the miscible or miscible state of semi-molten of fusion; 3) get active component, be heated to uniform temperature, add substrate then, continue to be heated to the miscible or miscible state of semi-molten of fusion; 4) get substrate, be heated to the miscible or miscible state of semi-molten of fusion, add active component then, mixing continues to be heated to the miscible or miscible state of semi-molten of fusion.
7. according to the described heating of claim 5, it is characterized in that: the miscible temperature of heating and melting is greater than 40 ℃.
8. pill according to claim 4 does not comprise drop pill.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102697819A (en) * | 2012-06-09 | 2012-10-03 | 东莞市照燕生物科技有限公司 | Nutritional health-care product for promoting male hormone |
| CN103989646A (en) * | 2014-05-29 | 2014-08-20 | 扬子江药业集团北京海燕药业有限公司 | Irbesartan medicinal composition, as well preparation method and application thereof |
| CN104983685A (en) * | 2015-06-25 | 2015-10-21 | 四川恒通动物制药有限公司 | Amoxicillin soluble powder and preparation method |
| CN105168145A (en) * | 2015-10-29 | 2015-12-23 | 林州中农生物肽科技有限公司 | Compound amoxycillin soluble powder and preparation method thereof |
| CN107520100A (en) * | 2016-09-13 | 2017-12-29 | 国药集团冯了性（佛山）药业有限公司 | Air-cooled disk honeyed bolus dips in wax machine and its application |
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- 2006-07-10 CN CNA2006100986340A patent/CN101023917A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102697819A (en) * | 2012-06-09 | 2012-10-03 | 东莞市照燕生物科技有限公司 | Nutritional health-care product for promoting male hormone |
| CN103989646A (en) * | 2014-05-29 | 2014-08-20 | 扬子江药业集团北京海燕药业有限公司 | Irbesartan medicinal composition, as well preparation method and application thereof |
| CN104983685A (en) * | 2015-06-25 | 2015-10-21 | 四川恒通动物制药有限公司 | Amoxicillin soluble powder and preparation method |
| CN105168145A (en) * | 2015-10-29 | 2015-12-23 | 林州中农生物肽科技有限公司 | Compound amoxycillin soluble powder and preparation method thereof |
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