CN104546767A - Fosfomycin calcium composition freeze-dried tablet and preparation method thereof - Google Patents
Fosfomycin calcium composition freeze-dried tablet and preparation method thereof Download PDFInfo
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- CN104546767A CN104546767A CN201410829509.7A CN201410829509A CN104546767A CN 104546767 A CN104546767 A CN 104546767A CN 201410829509 A CN201410829509 A CN 201410829509A CN 104546767 A CN104546767 A CN 104546767A
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Abstract
The invention provides a fosfomycin calcium composition freeze-dried tablet and a preparation method thereof, and relates to the technical field of medicines and medicine production. The fosfomycin calcium composition freeze-dried tablet comprises fosfomycin calcium, starch and cane sugar, wherein the starch and the cane sugar are used as auxiliary materials, and heating process processing is performed on common corn starch, so that the bonding and disintegrating functions of the starch in the tablet can be improved, and the formability of the tablet is improved; the fosfomycin calcium composition freeze-dried tablet only needs the starch and the cane sugar which are used as the auxiliary materials. The fosfomycin calcium composition freeze-dried tablet adopts a freeze-drying process that temperature is reduced and increased for two times, and the process that the temperature is reduced and increased for two times enables the formability of the tablet to be better, and increases the dissolution rate of the tablet, so that the bioavailability of the tablet is improved. The tablet disclosed by the invention overcomes the defects of a common fosfomycin calcium tablet, and has the characteristics that the types and the dosage of the auxiliary materials in the fosfomycin calcium tablet are reduced, the tablet has a high dissolution rate and high bioavailability, and the curative effect and the safety of clinical medication are guaranteed.
Description
Technical field
The present invention relates to medicine and medical production technical field, be specifically related to a kind of fosfomycin calcium composition freeze-drying sheet and preparation method thereof.
Background technology
Fosfomycin calcium antibiotics, for the simplex lower urinary tract infection caused by sensitive organism and intestinal infection.To enteritis, bacillary dysentery, urinary tract infection, skin and soft tissue infection, respiratory tract infection, dacryocystisis, hordeolum, vaginitis, cervicitis has remarkable effect.
Structural formula:
Molecular weight: 194.14
In common fosfomycin calcium tablet containing supplementary product kind and quantity more, generally to use filler, lubricant, disintegrating agent, adhesive, correctives etc., according to Chinese Pharmacopoeia (2010 editions) second fosfomycin calcium tablet quality standard, the dissolution of fosfomycin calcium tablet reached more than 75% for qualified 30 minutes time, and increasing research shows that impurity in the incompatibility of the toxic and side effects of adjuvant itself, adjuvant and principal agent, adjuvant etc. all can have an impact to the safety of medicine.
Therefore, provide one can overcome above-mentioned shortcoming, select suitable adjuvant and technique, reduce supplementary product kind and consumption in fosfomycin calcium tablet, improve dissolution and the bioavailability of fosfomycin calcium tablet, ensure that the safety of clinical application all has positive effect.
Traditional lyophilizing tablet can improve dissolution and bioavailability, but still need use the adjuvant such as mannitol, gelatin.And mannitol has certain biological activity, gelatin resource-constrained and perishable.
Starch is the basic adjuvant of oral solid formulation, it is polymerized by glucose molecule, and be commonly used for adhesive, diluent and disintegrating agent in tablets, it is cheap and easy to get, to human-body safety, but being used alone starch has no report as adjuvant freeze-dry process production fosfomycin calcium lyophilizing sheet.
Summary of the invention
Technical problem to be solved by this invention is the defect overcoming prior art, and propose a kind of fosfomycin calcium composition freeze-drying sheet and preparation method thereof further, said preparation adjuvant is few, good stability, and bioavailability is high.
Technical problem to be solved by this invention realizes by the following technical solutions:
A kind of fosfomycin calcium composition freeze-drying sheet, adjuvant is done with starch and sucrose, produce with freeze-dry process, this tablet overcomes the shortcoming of above-mentioned common fosfomycin calcium tablet, decrease supplementary product kind and consumption in fosfomycin calcium tablet, this sheet dissolution is large, and bioavailability is high, ensure that curative effect and the safety of clinical application.
A kind of fosfomycin calcium composition freeze-drying sheet, is prepared from by following raw material:
A preparation method for fosfomycin calcium composition freeze-drying sheet, comprises step as follows:
A, take the starch of component amount, add a certain amount of purified water and stir, by pH adjusting agent, the pH value of solution is controlled between 8.5-9.6, be then heated to 72 DEG C, be incubated 20 minutes, make the corn starch solution of 5 ~ 15% (W/V);
B, measure purified water 45ml, boil, add 85g sucrose, stir, after dissolving, continue to be heated to 100 DEG C, filter with purified cotton, the appropriate hot distilled water of filter is cleaned, and washing liquid and filtrate merge, and let cool, add appropriate distilled water, make full dose become 100m L, stir evenly, obtain B solution;
The solution that C, the solution and the step B that steps A are obtained obtain mixes, and fully stirs 30 minutes, is down to room temperature and obtains Semen Maydis-sucrose solution;
D, take fosfomycin calcium 100 grams, add in 1L Semen Maydis-sucrose solution, stir 25 ~ 35 minutes;
Medicinal liquid is sub-packed in drug-containing dish after measuring fosfomycin calcium content by E, medicinal liquid, each drug-containing dish dress 1.0ml;
F, the drug-containing dish that medicinal liquid is housed is put into vacuum freezing drying oven, be cooled to subzero 45 DEG C, keep 2 hours, evacuation, then 0 DEG C is warming up to gradually, keep 2 hours, then be cooled to subzero 45 DEG C, keep 2 hours, be warming up to 0 DEG C gradually again, keep 2 ~ 4 hours, then be warming up to 28 ~ 32 DEG C of dryings 4 ~ 6 hours gradually, whole process vacuum remains on 10 handkerchiefs; Finally the drug-containing dish lid of powder charge is covered tightly, and load aluminium foil bag and carry out sealing and obtain fosfomycin calcium composition freeze-drying sheet.
Described starch selects corn starch, preferably the corn starch solution of 10% (W/V).
Beneficial effect of the present invention is:
The preparation method of a kind of fosfomycin calcium composition freeze-drying sheet of the present invention, heating process process is carried out to common corn starch, starch bonding in tablets, disintegration can be improved, improve the mouldability of tablet, in fosfomycin calcium composition freeze-drying sheet, dosage of sucrose is 8.5% (W/V), it is the hardness reinforcer of this tablet, and plays flavored action.Fosfomycin calcium composition freeze-drying sheet only needs starch and sucrose two kinds of adjuvants.The freeze-dry process of two liters falls in fosfomycin calcium composition freeze-drying sheet employing two, and twice cooling, twice intensification can make sheet mouldability better, which increase the dissolution of tablet, thus improve the bioavailability of tablet.
Accompanying drawing explanation
Fig. 1 is the dissolution correlation curve figure of fosfomycin calcium in experiment.
Detailed description of the invention
The technological means realized to make the present invention, creation characteristic, reaching object and effect is easy to understand, below in conjunction with specific embodiment, set forth the present invention further, but following embodiment being only the preferred embodiments of the present invention, and not all.Based on the embodiment in embodiment, those skilled in the art under the prerequisite not making creative work obtain other embodiment, all belong to the protection domain of this patent.
Embodiment 1
A, take the corn starch of 100g, the purified water adding 900m l stirs, and controls at 8.5-9.6, is then heated to 72 DEG C, keep 120 minutes, make the corn starch solution of 9% (W/V) by pH adjusting agent by the pH value of solution.
B, measure purified water 45ml, boil, add 85g sucrose, stir, after dissolving, continue to be heated to 100 DEG C, filter with purified cotton, the appropriate hot distilled water of filter is cleaned, and washing liquid and filtrate merge, and let cool, add appropriate distilled water, make full dose become 100m L, stir evenly, obtain B solution.
The solution that C, the solution and the step B that steps A are obtained obtain mixes, and fully stirs 30 minutes, after solution be down to room temperature obtain Semen Maydis-sucrose solution.
D, take fosfomycin calcium 100g, add in 1L Semen Maydis-sucrose solution, stir 30 minutes.
Medicinal liquid is sub-packed in drug-containing dish after measuring fosfomycin calcium content by E, medicinal liquid, each drug-containing dish dress 1.0ml.
F, the drug-containing dish that medicinal liquid is housed is put into vacuum freezing drying oven, be cooled to subzero 45 DEG C, keep 2 hours, evacuation, then 0 DEG C is warming up to gradually, keep 2 hours, then be cooled to subzero 45 DEG C, keep 2 hours, be warming up to 0 DEG C gradually again, keep 2 ~ 4 hours, then be warming up to 28 ~ 32 DEG C of dryings 4 ~ 6 hours gradually, whole process vacuum remains on 10 handkerchiefs.Finally the drug-containing dish lid of powder charge is covered tightly, and load aluminium foil bag and carry out sealing and obtain fosfomycin calcium composition freeze-drying sheet.
Embodiment 2
A, take the corn starch of 130g, the purified water adding 900ml stirs, and controls at 8.5-9.6, is then heated to 72 DEG C, keep 120 minutes, make the corn starch solution of 13% (W/V) by pH adjusting agent by the pH value of solution.
B, measure purified water 45ml, boil, add 85g sucrose, stir, after dissolving, continue to be heated to 100 DEG C, filter with purified cotton, the appropriate hot distilled water of filter is cleaned, and washing liquid and filtrate merge, and let cool, add appropriate distilled water, make full dose become 100m L, stir evenly, obtain B solution.
The solution that C, the solution and the step B that steps A are obtained obtain mixes, and fully stirs 30 minutes, after solution be down to room temperature obtain Semen Maydis-sucrose solution.
D, take fosfomycin calcium 100 grams (by 1000 calculations), add 1L Semen Maydis-sucrose solution, stir 30 minutes.
Medicinal liquid is sub-packed in drug-containing dish after measuring fosfomycin calcium content by E, medicinal liquid, each drug-containing dish dress 1.0ml.
F, the drug-containing dish that medicinal liquid is housed is put into vacuum freezing drying oven, be cooled to subzero 45 DEG C, keep 2 hours, evacuation, then 0 DEG C is warming up to gradually, keep 2 hours, then be cooled to subzero 45 DEG C, keep 2 hours, be warming up to 0 DEG C gradually again, keep 2 ~ 4 hours, then be warming up to 28 ~ 32 DEG C of dryings 4 ~ 6 hours gradually, whole process vacuum remains on 10 handkerchiefs.Finally the drug-containing dish lid of powder charge is covered tightly, and load aluminium foil bag and carry out sealing and obtain fosfomycin calcium composition freeze-drying sheet.
Experimental data
The fosfomycin calcium composition freeze-drying sheet that above-described embodiment is obtained carries out following quality research test:
1, hardness, friability contrast test
Get fosfomycin calcium composition freeze-drying sheet prepared by above-described embodiment respectively and fosfomycin calcium ordinary tablet (commercially available) detects friability and hardness by " Chinese Pharmacopoeia " version in 2010 two annex X G inspection techniques, carried out comparative study, the results are shown in following table:
| Sample | Hardness/N | Friability |
| Execute example 1 | 63 | <1％ |
| Execute example 2 | 68 | <1％ |
| Ordinary tablet | 69 | <1％ |
Experimental data shows, fosfomycin calcium composition freeze-drying sheet and ordinary tablet (commercially available) without significant difference, meet " Chinese Pharmacopoeia " version in 2010 to the requirement of tablet on friability and hardness.
2, dissolution contrast test
(No. 1 to No. 3 is embodiment 1 to get fosfomycin calcium tablet (commercially available) and each 6 of fosfomycin calcium lyophilizing sheet, No. 4 to No. 6 is embodiment 2), press Chinese Pharmacopoeia (2010 editions) second dissolution method annex X C second method respectively, with 0.lmol/L hydrochloric acid solution 1000ml for dissolution medium, rotating speed is 75 turns per minute, operate in accordance with the law, respectively at 10min, 20min, 30min, 40min, during 60min, get solution appropriate, the solution made about containing fosfomycin 0.lmg in every lm is quantitatively diluted with dissolution medium, filter, precision measures subsequent filtrate 5ml, put in 25ml measuring bottle, separately get this product 10, accurately weighed, porphyrize, precision takes in right amount (being about equivalent to average sheet weight), and add dissolution medium, jolting makes Fosfomycin calcium dissolve, and quantitatively the solution about containing fosfomycin 0.lmg in every lml is made in dilution, filter, precision measures subsequent filtrate 5ml, puts in another 25m l measuring bottle.Add freshly prepared ammonium persulfate solution respectively (to get Ammonium persulfate. 1g to add water 15ml, shake up, make dissolving) lml, with a small amount of water rinsing bottle wall, water-bath boils 10 minutes, take out, add people 1% urea liquid 2ml, boil 10 minutes again, take out, after being cooled to room temperature, add people 5% molybdic acid hinge solution again and (get ammonium molybdate 10g, add the sulfuric acid solution 100ml of 5mol/L, make dissolving, add water to 200ml, shaking up) 1.5ml and 0.5% sodium sulfite solution (get sodium sulfite 0.5g, the 80ml that adds water makes dissolving, add people's p-methylaminophenol sulfate 0.2g again, sodium metabisulfite 30g, jolting makes dissolving, add water to 100ml, shake up) lml, be diluted with water to scale, room temperature places 20 minutes, as need testing solution and contrast solution, getting need testing solution and contrast solution, take water as blank, according to ultraviolet visible spectrophotometry (annex WA), measures absorbance respectively, calculate the stripping quantity of every sheet at the wavelength place of 650nm.
One, fosfomycin calcium tablet (commercially available)
Two, fosfomycin calcium lyophilizing sheet (No. 1 to No. 3 is embodiment 1, and No. 4 to No. 6 is embodiment 2)
Respectively with catch cropping Dissolution profiles during average dissolution pair, as Fig. 1.
Four, result judges
Judge according to Chinese Pharmacopoeia (2010 editions) second fosfomycin calcium tablet quality standard, the dissolution of fosfomycin calcium tablet (commercially available) reached more than 75% for qualified 30 minutes time, actual measurement is 76.3%, and fosfomycin calcium lyophilizing sheet dissolution 20 minutes time reaches 77.3%.It can thus be appreciated that the time that fosfomycin calcium lyophilizing sheet dissolution reaches 75% decreased for about 33.3% (10 minutes) time than fosfomycin calcium tablet (commercially available).So the fosfomycin calcium lyophilizing sheet blood drug level peaking time is shorter than fosfomycin calcium tablet (commercially available), and bioavailability is higher, better efficacy.
More than show and describe ultimate principle of the present invention, principal character and advantage of the present invention.The technical staff of the industry should understand; the present invention is not restricted to the described embodiments; what describe in above-described embodiment and description is only preference of the present invention; be not used for limiting the present invention; without departing from the spirit and scope of the present invention; the present invention also has various changes and modifications, and these changes and improvements all fall in the claimed scope of the invention.Application claims protection domain is defined by appending claims and equivalent thereof.
Claims (2)
1. a fosfomycin calcium composition freeze-drying sheet, is characterized in that, is prepared from by following raw material:
2. a preparation method for fosfomycin calcium composition freeze-drying sheet according to claim 1, is characterized in that, comprise step as follows:
A, take the starch of component amount, add a certain amount of purified water and stir, by pH adjusting agent, the pH value of solution is controlled between 8.5-9.6, be then heated to 72 DEG C, be incubated 20 minutes, make the corn starch solution of 5 ~ 15% (W/V);
B, measure purified water 45ml, boil, add 85g sucrose, stir, after dissolving, continue to be heated to 100 DEG C, filter with purified cotton, the appropriate hot distilled water of filter is cleaned, and washing liquid and filtrate merge, and let cool, add appropriate distilled water, make full dose become 100mL, stir evenly, obtain B solution;
The solution that C, the solution and the step B that steps A are obtained obtain mixes, and fully stirs 30 minutes, is down to room temperature and obtains Semen Maydis-sucrose solution;
D, take fosfomycin calcium 100 grams, add in 1L Semen Maydis-sucrose solution, stir 25 ~ 35 minutes;
Medicinal liquid is sub-packed in drug-containing dish after measuring fosfomycin calcium content by E, medicinal liquid, each drug-containing dish dress 1.0ml;
F, the drug-containing dish that medicinal liquid is housed is put into vacuum freezing drying oven, be cooled to subzero 45 DEG C, keep 2 hours, evacuation, then 0 DEG C is warming up to gradually, keep 2 hours, then be cooled to subzero 45 DEG C, keep 2 hours, be warming up to 0 DEG C gradually again, keep 2 ~ 4 hours, then be warming up to 28 ~ 32 DEG C of dryings 4 ~ 6 hours gradually, whole process vacuum remains on 10 handkerchiefs; Finally the drug-containing dish lid of powder charge is covered tightly, and load aluminium foil bag and carry out sealing and obtain fosfomycin calcium composition freeze-drying sheet.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106949710A (en) * | 2017-04-17 | 2017-07-14 | 千辉药业（安徽）有限责任公司 | A kind of drying means of fosfomycin calcium |
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| JPS61242556A (en) * | 1985-04-19 | 1986-10-28 | Hatoya Seika:Kk | Preparation of snack using fruits |
| US20020173016A1 (en) * | 2001-03-27 | 2002-11-21 | Helmut Wurst | High-throughput nucleic acid polymerase devices and methods for their use |
| CN102784118A (en) * | 2012-08-23 | 2012-11-21 | 海南卫康制药(潜山)有限公司 | Fosfomycin calcium composition freeze-dried orally disintegrating tablets and preparation method thereof |
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2014
- 2014-12-25 CN CN201410829509.7A patent/CN104546767A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| JPS61242556A (en) * | 1985-04-19 | 1986-10-28 | Hatoya Seika:Kk | Preparation of snack using fruits |
| US20020173016A1 (en) * | 2001-03-27 | 2002-11-21 | Helmut Wurst | High-throughput nucleic acid polymerase devices and methods for their use |
| CN102784118A (en) * | 2012-08-23 | 2012-11-21 | 海南卫康制药(潜山)有限公司 | Fosfomycin calcium composition freeze-dried orally disintegrating tablets and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106949710A (en) * | 2017-04-17 | 2017-07-14 | 千辉药业（安徽）有限责任公司 | A kind of drying means of fosfomycin calcium |
| CN106949710B (en) * | 2017-04-17 | 2019-11-05 | 千辉药业（安徽）有限责任公司 | A kind of drying means of fosfomycin calcium |
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Application publication date: 20150429 |