CN103040833A - Pharmaceutical composition of voriconazole and preparation method - Google Patents
Pharmaceutical composition of voriconazole and preparation method Download PDFInfo
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- CN103040833A CN103040833A CN2012103805200A CN201210380520A CN103040833A CN 103040833 A CN103040833 A CN 103040833A CN 2012103805200 A CN2012103805200 A CN 2012103805200A CN 201210380520 A CN201210380520 A CN 201210380520A CN 103040833 A CN103040833 A CN 103040833A
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- voriconazole
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Abstract
The invention provides a pharmaceutical composition of voriconazole and a preparation method. The composition mainly comprises voriconazole, polyethylene glycol melting agent 6000 and other auxiliaries. The preparation method comprises the steps of uniformly mixing the voriconazole with various auxiliaries, preparing medicament particles by using a hot-melting granulation technology, pressing the particles to be tablets and coating.
Description
Technical field
The present invention proposes and novel prepare the voriconazole granule with hot melt, belong to field of medicaments.
Background technology
Voriconazole is a kind of triazole antifungal agent of wide spectrum, and its indication is as follows: the treatment Aspergillosis.Treatment is dyed (comprising Candida krusei) to the microbial bad attack sexuality of the beads of fluconazol drug resistance.The severe infections that treatment is caused by Scedosporium and Fusarium.Voriconazole chemical name: (2R, 3S)-2-(2,4 difluorobenzene base)-3-(5-fluoro-4-pyrimidine)-1-(1H-1,2,4-triazol-1-yl)-2-butanols.
The conventional film-making of voriconazole is the wet method film-making, in conventional wet is granulated, consider to add amount of binder, particle drying time, the factor such as time of sieving of granulating, the machine quantity of need of production is many, the space is large, and because some factor need to rely on micro-judgment, therefore may cause unstable product quality, batch difference is large etc.
Hot melt is emerging technology recent years, and granulating to compare with conventional wet only needs fluid bed to finish, and fluid bed is the common equipment of modern pharmaceutical.The method is time saving and energy saving, and is convenient to operation, saves cost.
Summary of the invention
Purpose of the present invention provides a kind of voriconazole drug regimen hot melt to prepare the preparation method of granule.
The technical scheme of this invention is as follows: voriconazole is mixed with the other drug adjuvant, granulate by hot melt, the granule tabletting that makes is made tablet.
Tablet is preferred, and thin membrane coated tablet more preferably.
The method is compared with wet granulation, and its operating process is more easy, and granule is faster than the wet granulation stripping simultaneously, also can consider to make capsule, and capital equipment is fluid bed simultaneously.Its principle is with main and adjuvant mixed melting in the adjuvant groove, be delivered to the refrigerating chamber gas nozzle by the constant voltage thermostat, compressed air atomizing by air compressor machine is small droplet, be cured as in the powder cup that is deposited to hothouse by chilled air cools again, tail wind gas solid separation in cyclone separator of atomization refrigeration chamber, product is caught in the powder cup, and tail gas enters atmosphere by air-introduced machine.
This drug regimen is polyethylene glycol 6000, voriconazole and other pharmaceutic adjuvants.
The pharmaceutic adjuvant disintegrating agent is selected from the crosslinked Ju Wei of Suo methyl starch Na ﹑ Tong ﹑ cross-linking sodium carboxymethyl cellulose; Lubricant is selected from the stearic acid Mei ﹑ Pulvis Talci; Binding agent is selected from Ju Wei Tong ﹑ Qiang propyl group Xian Wei Su ﹑ starch; Filler is selected from pre-paying of Ru Tang ﹑ Wei crystalline cellulose Su ﹑ Dian Fen ﹑ mannitol.
The monolithic drug content is the 200mg specification, adds simultaneously the polyethylene glycol 6000 of 12-42mg,
Be preferably:
Voriconazole 200mg
Disintegrating agent 18-32mg
Binding agent 18-32mg
Filler 300-378mg
Polyethylene glycol 6000 12-42mg
Lubricant 3-12mg
Coating powder 12-36mg
More preferably:
Voriconazole 200mg
Cross-linking sodium carboxymethyl cellulose 18-32mg
Polyvidone 18-32mg
Lactose 240-300mg
Pregelatinized Starch 72-90mg
Polyethylene glycol 6000 18-40mg
Opadry 31K58875 white coating powder 24-36mg
Magnesium stearate 6mg
All be that voriconazole is made tablet with preferred two schemes preferably.
The present invention is not limited to 200mg, and other specification is applicable too, also is not limited to tablet, and capsule is also applicable.
Preferred version is voriconazole 200mg, cross-linking sodium carboxymethyl cellulose 18-32mg, polyvidone 18-32mg, lactose 240-300mg, pregelatinized Starch 72-90mg, polyethylene glycol 6000 18-40mg, Opadry 31K58875 white coating powder 24-36mg, magnesium stearate 3-12mg.
Optimal case is voriconazole 200mg, cross-linking sodium carboxymethyl cellulose 20-28mg, polyvidone 18-25mg, lactose 240-300mg, pregelatinized Starch 72-90mg, polyethylene glycol 6000 24-36mg, Opadry 31K58875 white coating powder 24-30mg, magnesium stearate 6mg.
The dissolution rate of the gained granule medicament of this programme obviously increases, and also can increase the bioavailability of medicine simultaneously, has increased the effect of its broad-spectrum antifungal.
The specific embodiment
Implement one
Voriconazole fine powder 200mg evenly mixed with pre-paying of cross-linking sodium carboxymethyl cellulose 18mg ﹑ polyethylene glycol 6000 18mg ﹑ polyvidone 18mg ﹑ lactose 270mg ﹑ starch 80mg be placed in the fluid bed, wind is 40Hz frequently, 58 ℃ of temperature of charge, heating 10min carries out hot melt and granulates, at last granule is mixed with magnesium stearate 3mg, be pressed into tablet, use again the Opadry coating.
Implement two
Voriconazole fine powder 200mg evenly mixed with pre-paying of cross-linking sodium carboxymethyl cellulose 25mg ﹑ polyethylene glycol 6000 30mg ﹑ polyvidone 25mg ﹑ lactose 270mg ﹑ starch 80mg be placed in the fluid bed, wind is 50Hz frequently, 68 ℃ of temperature of charge, heating 10min carries out hot melt and granulates, at last granule is mixed with magnesium stearate 6mg, be pressed into tablet, use again the Opadry coating.
Implement three
Voriconazole fine powder 200mg evenly mixed with pre-paying of cross-linking sodium carboxymethyl cellulose 32mg ﹑ polyethylene glycol 6000 40mg ﹑ polyvidone 32mg ﹑ lactose 270mg ﹑ starch 80mg be placed in the fluid bed, wind is 60Hz frequently, 78 ℃ of temperature of charge, heating 10min carries out hot melt and granulates, at last granule is mixed with magnesium stearate 6mg, be pressed into tablet, use again the Opadry coating.
[0019] Fig. 1 is relatively seen in each case study on implementation and wet granulation stripping.
Wet granulation is slow many with hot melt phase intrisinc rate of dissolution as seen from Figure 1, has also caused the onset of medicine slow, and bioavailability is low.
Description of drawings
Fig. 1 is each case study on implementation and wet granulation stripping comparison diagram.
Fig. 2 is case study on implementation and wet granulation stripping curve figure.
Claims (9)
1. the drug regimen take voriconazole as principal agent is characterized in that it is comprised of voriconazole and polyethylene glycol 6000 and other drug adjuvant.
2. drug regimen according to claim 1 is characterized in that this combination is by hot melt granulation technique granulation gained.
3. drug regimen according to claim 1, the temperature of charge when it is characterized in that granulating is 50-80 ℃.
4. drug regimen according to claim 1 is characterized in that its excipient substance selection disintegrating agent, lubricant, binding agent and filler.
5. according to claim 4, it is characterized in that disintegrating agent is selected from one or more of the crosslinked Ju Wei of Suo methyl starch Na ﹑ Tong ﹑ cross-linking sodium carboxymethyl cellulose; Lubricant is selected from one or both in the stearic acid Mei ﹑ Pulvis Talci; Binding agent is selected from one or more in the Ju Wei Tong ﹑ Qiang propyl group Xian Wei Su ﹑ starch; Filler is selected from one or more in pre-paying of the Ru Tang ﹑ Wei crystalline cellulose Su ﹑ Dian Fen ﹑ mannitol.
6. according to claim 4, it is characterized in that the monolithic composition and ratio is as follows:
Voriconazole 200mg
Disintegrating agent 18-32mg
Binding agent 18-32mg
Filler 300-378mg
Polyethylene glycol 6000 12-42mg
Lubricant 3-12mg
Coating powder 12-36mg.
7. according to claim 6, it is characterized in that respectively forming adjuvant is allocated as follows:
Voriconazole 200mg
Cross-linking sodium carboxymethyl cellulose 18-32mg
Polyvidone 18-32mg
Lactose 240-300mg
Pregelatinized Starch 72-90mg
Polyethylene glycol 6000 18-40mg
Opadry 31K58875 white coating powder 24-36mg
Magnesium stearate 6mg.
8. drug regimen according to claim 1 is characterized in that preparation method is: sugared pre-paying of the ﹑ starch of the poly-dimension of Fu Likang azoles ﹑ Macrogol 600 0 ﹑ ketone ﹑ breast is put in hot melt granulation in the fluid bed.
9. according to right 8 described preparation methoies, it is characterized in that: the voriconazole fine powder is evenly mixed being placed in the fluid bed with cross-linked carboxymethyl fiber Su Na ﹑ Macrogol 600 0 pre-paying of ﹑ Ju Wei Tong ﹑ Ru Tang ﹑ starch by the described proportioning of claim, wind is 40-60Hz frequently, temperature of charge 50-80 ℃, heating 10min carries out hot melt and granulates, at last granule is mixed with magnesium stearate, tabletting is used the Opadry coating again.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012103805200A CN103040833A (en) | 2012-10-10 | 2012-10-10 | Pharmaceutical composition of voriconazole and preparation method |
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| Application Number | Priority Date | Filing Date | Title |
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| CN2012103805200A CN103040833A (en) | 2012-10-10 | 2012-10-10 | Pharmaceutical composition of voriconazole and preparation method |
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| CN103040833A true CN103040833A (en) | 2013-04-17 |
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| CN2012103805200A Pending CN103040833A (en) | 2012-10-10 | 2012-10-10 | Pharmaceutical composition of voriconazole and preparation method |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016037463A (en) * | 2014-08-07 | 2016-03-22 | 共和薬品工業株式会社 | Pharmaceutical composition containing voriconazole |
| CN112353769A (en) * | 2020-11-26 | 2021-02-12 | 珠海亿邦制药有限责任公司 | Method for preparing voriconazole tablets by powder direct compression method |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101951891A (en) * | 2008-01-11 | 2011-01-19 | 希普拉有限公司 | Solid pharmaceutical dosage form |
| CN102058519A (en) * | 2010-11-19 | 2011-05-18 | 苏州特瑞药业有限公司 | Voriconazole slow-release suppository and preparation method thereof |
-
2012
- 2012-10-10 CN CN2012103805200A patent/CN103040833A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101951891A (en) * | 2008-01-11 | 2011-01-19 | 希普拉有限公司 | Solid pharmaceutical dosage form |
| CN102058519A (en) * | 2010-11-19 | 2011-05-18 | 苏州特瑞药业有限公司 | Voriconazole slow-release suppository and preparation method thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016037463A (en) * | 2014-08-07 | 2016-03-22 | 共和薬品工業株式会社 | Pharmaceutical composition containing voriconazole |
| CN112353769A (en) * | 2020-11-26 | 2021-02-12 | 珠海亿邦制药有限责任公司 | Method for preparing voriconazole tablets by powder direct compression method |
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Application publication date: 20130417 |