CN103446066B - Paroxetine liensinine freeze-dried powder and preparation method thereof - Google Patents
Paroxetine liensinine freeze-dried powder and preparation method thereof Download PDFInfo
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- CN103446066B CN103446066B CN201310420340.5A CN201310420340A CN103446066B CN 103446066 B CN103446066 B CN 103446066B CN 201310420340 A CN201310420340 A CN 201310420340A CN 103446066 B CN103446066 B CN 103446066B
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Abstract
The invention relates to a paroxetine liensinine freeze-dried powder, which is prepared from the following raw materials: 22 g of paroxetine, 16 g of tartaric acid, 8 g of citric acid, 48 g of polyethylene glycol 800, and 2000 ml of water for injection. The pH is adjusted to the range from 6.6 to 6.8.
Description
Technical field
The present invention relates to paroxetine freeze-dried powder and preparation method thereof.Background technology
Paroxetine (-) 2paroxetine, be that Glaxo Smith Kline company of the U.S. develops, in the anti-depression drug of approval listing in 1992, usually used as medicinal application is its hydrochlorate.Paroxetine can make 5-hydroxy tryptamine in synaptic space (5-HT) concentration increase, play antidepressant effect, more weak to other Neurotransmitters, less on the unify impact of cardiovascular system of autonomic nerve system, be selectivity nervus centralis 52 hydroxytryptamine (52HT) reuptake inhibitor (SSRI).Be mainly used in Cure of depression clinically, also can treat the diseases such as obsession, panic disorder or social anxiety disorder.At present, it and fluoxetine, Sertraline be called the large anti-depression drug in the world three.Dosage form mainly tablet, the micropill of current paroxetine.CN1568987A discloses a kind of paroxetine drop pill, and CN102525966A discloses a kind of paroxetine tablet.
In order to be more suitable for the needs of patient in dosage form, except oral tablet, also need to develop other dosage forms.But the dissolubility of paroxetine in a lot of solvent is low, the object changing dosage form is made to be difficult to reach.
Summary of the invention
The invention provides a kind of stable paroxetine freeze-dried powder and preparation method thereof, described paroxetine freeze-dried powder adjuvant is less, and good stability, Clinical practice safety is higher.
Technical scheme provided by the invention is: paroxetine freeze-dried powder, is made up of following raw material: 22g paroxetine, 16g tartaric acid, 8g citric acid, 48g polyethylene glycol-800,2000ml water for injection; Adjust pH to 6.6 ~ 6.8.
Its mesotartaric acid and citric acid also serve the effect of antioxidant while playing cosolvent.
Present invention also offers the preparation method of above-mentioned paroxetine freeze-dried powder:
1, get tartaric acid and the citric acid of recipe quantity, add the water for injection of 50% amount, be heated to 50 ~ 55 DEG C, stir and make it dissolve, the paroxetine getting recipe quantity adds in solution, continues stirring 15 minutes after stirring and dissolving.
2, get the polyethylene glycol-800 of recipe quantity, add the water for injection of 40% amount, stir 15 minutes, adjust PH to 3.0 ~ 3.5 with hydrochloric acid (hydrochloric acid of preferred 1mol/L).
3,1,2 solution are merged, adjust PH to 6.6 ~ 6.8 with PH regulator (sodium hydroxide solution of preferred 1mol/L), add to the full amount of water for injection, add the needle-use activated carbon of 0.15%, stir 25 minutes, filter decarburization, intermediate checks, qualified rear use 0.22 μm of membrane filtration is degerming.
4, filtrate is poured in cillin bottle, carry out lyophilization, obtain freeze-dried powder, after the assay was approved, packaging.
Inventor finds amazedly, the tartaric acid of use specified quantitative and the combination of citric acid are as cosolvent, and the Polyethylene Glycol of the use polyethylene glycol-800 of specified quantitative instead of other molecular weight is as frozen-dried supporting agent, the paroxetine lyophilized injectable powder stability prepared is high, and its related substances is few.Further, paroxetine freeze-dried powder adjuvant of the present invention is less, and good stability, Clinical practice safety is higher.
Detailed description of the invention
Below test further illustrates the present invention:
the investigation of cosolvent
The dissolving of paroxetine needs acid cosolvent, and we investigate several cosolvent.Respectively get 1g paroxetine to add and in advance adjust pH value to be in the 200ml water of about 6.6 ~ 6.8 with various cosolvent respectively.Place 10 days at 60 DEG C, investigate the change of paroxetine content, the results are shown in Table 1:
Table 1
Result of the test surface, place after 10 days for 60 DEG C, the paroxetine content that various cosolvent dissolves has obvious decline, but declines obvious less with the sample size that tartaric acid and citric acid composition make cosolvent.
Further research we surprisingly find that the tartaric acid of specified quantitative and the conbined usage of citric acid and polyethylene glycol-800 serve beyond thought remarkable result to the quality stability improving paroxetine.
Embodiment 1:
Paroxetine: 22g
Tartaric acid and citric acid: 16g tartaric acid+8g citric acid
Polyethylene glycol-800: 48g
PH regulator: appropriate
Water for injection: 2000ml
Technique:
1, get tartaric acid and the citric acid of recipe quantity, add 50% water for injection, be heated to 50 ~ 55 DEG C, stir and make it dissolve, the paroxetine getting recipe quantity adds in solution, continues stirring 15 minutes after stirring and dissolving.
2, get the polyethylene glycol-800 of recipe quantity, add 40% water for injection, stir 15 minutes, adjust pH to 3.0 ~ 3.5 with hydrochloric acid.
3,1,2 solution are merged, adjust pH to 6.6 ~ 6.8 by pH adjusting agent (sodium hydroxide solution), add to the full amount of water for injection, add the needle-use activated carbon of 0.15%, stir 25 minutes, filter decarburization, intermediate inspection, qualified rear use 0.22 μm of membrane filtration is degerming, filtrate is poured in cillin bottle, carry out lyophilization, obtain freeze-dried powder, after the assay was approved, pack.
Comparative examples 1:
Paroxetine: 22g
Tartaric acid and citric acid: 16g tartaric acid+8g citric acid
PH regulator: appropriate
Water for injection: 2000ml
Technique:
1, get tartaric acid and the citric acid of recipe quantity, add 80% water for injection, be heated to 50 ~ 55 DEG C, stir and make it dissolve, the paroxetine getting recipe quantity adds in solution, continues stirring 15 minutes after stirring and dissolving.
2, PH to 6.6 ~ 6.8 are adjusted by pH adjusting agent (sodium hydroxide solution), add to the full amount of water for injection, add the needle-use activated carbon of 0.15%, stir 25 minutes, filter decarburization, intermediate checks, qualified rear use 0.22 μm of membrane filtration is degerming, filtrate is poured in cillin bottle, carry out lyophilization, obtain freeze-dried powder, after the assay was approved, packaging.
Comparative examples 2:
Paroxetine: 22g
Polyethylene glycol-800: 48g
PH adjusting agent: appropriate
Water for injection: 2000ml
Technique:
1, get the polyethylene glycol-800 of recipe quantity, add 80% water for injection, stir 15 minutes, adjust pH to 3.0 ~ 3.5 with hydrochloric acid.The paroxetine getting recipe quantity adds in solution, continues stirring 15 minutes after stirring and dissolving.
2, PH to 6.6 ~ 6.8 are adjusted by pH adjusting agent (sodium hydroxide solution), add to the full amount of water for injection, add the needle-use activated carbon of 0.15%, stir 25 minutes, filter decarburization, intermediate checks, qualified rear use 0.22 μm of membrane filtration is degerming, filtrate is poured in cillin bottle, carry out lyophilization, obtain freeze-dried powder, after the assay was approved, packaging.
Comparative examples 3:
Paroxetine: 22g
Tartaric acid and citric acid: 16g tartaric acid+8g citric acid
Polyethylene glycol 6000: 48g
PH regulator: appropriate
Water for injection: 2000ml
Technique:
1, get tartaric acid and the citric acid of recipe quantity, add 50% water for injection, be heated to 50 ~ 55 DEG C, stir and make it dissolve, the paroxetine getting recipe quantity adds in solution, continues stirring 15 minutes after stirring and dissolving.
2, get the polyethylene glycol 6000 of recipe quantity, add 40% water for injection, stir 15 minutes, adjust pH to 3.0 ~ 3.5 with hydrochloric acid.
3,1,2 solution are merged, adjust pH to 6.6 ~ 6.8 by pH adjusting agent (sodium hydroxide solution), add to the full amount of water for injection, add the needle-use activated carbon of 0.15%, stir 25 minutes, filter decarburization, intermediate inspection, qualified rear use 0.22 μm of membrane filtration is degerming, filtrate is poured in cillin bottle, carry out lyophilization, obtain freeze-dried powder, after the assay was approved, pack.
Comparative examples 4:
Paroxetine: 22g
Tartaric acid: 24g
Polyethylene glycol-800: 48g
PH regulator: appropriate
Water for injection: 2000ml
Technique:
1, get the tartaric acid of recipe quantity, add 50% water for injection, be heated to 50 ~ 55 DEG C, stir and make it dissolve, the paroxetine getting recipe quantity adds in solution, continues stirring 15 minutes after stirring and dissolving.
2, get the polyethylene glycol-800 of recipe quantity, add 40% water for injection, stir 15 minutes, adjust pH to 3.0 ~ 3.5 with hydrochloric acid.
3,1,2 solution are merged, adjust pH to 6.6 ~ 6.8 by pH adjusting agent (sodium hydroxide solution), add to the full amount of water for injection, add the needle-use activated carbon of 0.15%, stir 25 minutes, filter decarburization, intermediate inspection, qualified rear use 0.22 μm of membrane filtration is degerming, filtrate is poured in cillin bottle, carry out lyophilization, obtain freeze-dried powder, after the assay was approved, pack.
Comparative examples 5:
Paroxetine: 22g
Lactic acid: 24g
Polyethylene glycol-800: 48g
PH regulator: appropriate
Water for injection: 2000ml
Technique:
1, get the tartaric acid of recipe quantity, add 50% water for injection, be heated to 50 ~ 55 DEG C, stir and make it dissolve, the paroxetine getting recipe quantity adds in solution, continues stirring 15 minutes after stirring and dissolving.
2, get the polyethylene glycol-800 of recipe quantity, add 40% water for injection, stir 15 minutes, adjust pH to 3.0 ~ 3.5 with hydrochloric acid.
3,1,2 solution are merged, adjust pH to 6.6 ~ 6.8 by pH adjusting agent (sodium hydroxide solution), add to the full amount of water for injection, add the needle-use activated carbon of 0.15%, stir 25 minutes, filter decarburization, intermediate inspection, qualified rear use 0.22 μm of membrane filtration is degerming, filtrate is poured in cillin bottle, carry out lyophilization, obtain freeze-dried powder, after the assay was approved, pack.
Comparative examples 6:
Paroxetine: 15g
Tartaric acid and citric acid: 5g tartaric acid+15g citric acid
Polyethylene glycol-800: 30g
PH regulator: appropriate
Water for injection: 2000ml
Technique:
1, get tartaric acid and the citric acid of recipe quantity, add 50% water for injection, be heated to 50 ~ 55 DEG C, stir and make it dissolve, the paroxetine getting recipe quantity adds in solution, continues stirring 15 minutes after stirring and dissolving.
2, get the polyethylene glycol-800 of recipe quantity, add 40% water for injection, stir 15 minutes, adjust pH to 3.0 ~ 3.5 with hydrochloric acid.
3,1,2 solution are merged, adjust pH to 6.6 ~ 6.8 by pH adjusting agent (sodium hydroxide solution), add to the full amount of water for injection, add the needle-use activated carbon of 0.15%, stir 25 minutes, filter decarburization, intermediate inspection, qualified rear use 0.22 μm of membrane filtration is degerming, filtrate is poured in cillin bottle, carry out lyophilization, obtain freeze-dried powder, after the assay was approved, pack.
The product that above-mentioned 7 embodiments are obtained is positioned in 60 DEG C of climatic chambers, and in sampling calibrating in the 5th, 10 day, result compared with 0 day:
Related substance, content are by high effective liquid chromatography for measuring (be shown in table 2).
Table 2
Result shows: embodiment 1 compares with comparative examples 1-6, and pH, related substance, stable content have obvious advantage, and the conbined usage of the tartaric acid of specified quantitative, citric acid and polyethylene glycol-800 has comparatively been used alone obvious advantage.
The paroxetine freeze-dried powder embodiment of the present invention 1 prepared and comparative examples 1-6 carry out long-time stability investigation (25 DEG C ± 2 DEG C, RH 60% ± 10%), the results are shown in Table 5:
Table 5
Result shows: paroxetine freeze-dried powder (embodiment 1) prepared by the present invention is compared with comparative examples 1-7, and quality stability increases significantly.
Claims (2)
1. paroxetine freeze-dried powder, wherein active component is paroxetine, and it is made up of following raw material: 22g paroxetine, 16g tartaric acid, 8g citric acid, 48g polyethylene glycol-800,2000ml water for injection; Adjust pH to 6.6 ~ 6.8.
2. the preparation method of the paroxetine freeze-dried powder as described in claim 1:
(1) get tartaric acid and the citric acid of recipe quantity, add the water for injection of 50% amount, be heated to 50 ~ 55 DEG C of stirrings and make it dissolve, the paroxetine getting recipe quantity adds in solution and continues stirring after stirring and dissolving 15 minutes;
(2) get the polyethylene glycol-800 of recipe quantity, the water for injection adding 40% amount stirs adjusts pH to 3.0 ~ 3.5 with hydrochloric acid in 15 minutes;
(3) merged by 1,2 solution, adjust pH to 6.6 ~ 6.8 with pH regulator, add to the full amount of water for injection, add the needle-use activated carbon of 0.15%, stir 25 minutes filtering decarbonizations, intermediate inspection, qualified rear use 0.22 μm of membrane filtration is degerming;
(4) filtrate is poured in cillin bottle, carry out lyophilization, obtain freeze-dried powder, after the assay was approved, packaging.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201310420340.5A CN103446066B (en) | 2013-09-16 | 2013-09-16 | Paroxetine liensinine freeze-dried powder and preparation method thereof |
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| CN201310420340.5A CN103446066B (en) | 2013-09-16 | 2013-09-16 | Paroxetine liensinine freeze-dried powder and preparation method thereof |
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| CN103446066A CN103446066A (en) | 2013-12-18 |
| CN103446066B true CN103446066B (en) | 2014-12-24 |
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Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| GB0308968D0 (en) * | 2003-04-17 | 2003-05-28 | Glaxo Group Ltd | Medicaments |
| US20090227682A1 (en) * | 2008-03-04 | 2009-09-10 | Pharma Pass Ii Llc | Xetine compositions |
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