CN101522223A - Process for the preparation of solid sterile active pharmaceutical ingredient - Google Patents
Process for the preparation of solid sterile active pharmaceutical ingredient Download PDFInfo
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- CN101522223A CN101522223A CNA2007800276024A CN200780027602A CN101522223A CN 101522223 A CN101522223 A CN 101522223A CN A2007800276024 A CNA2007800276024 A CN A2007800276024A CN 200780027602 A CN200780027602 A CN 200780027602A CN 101522223 A CN101522223 A CN 101522223A
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Abstract
The present invention provides a method of preparing a packed sterile solid active pharmaceutical ingredient, in particular sterile steroids such as a glucocorticosteroid acid.
Description
The cross reference of related application
The application requires the rights and interests of following U.S. Provisional Patent Application: the 60/832nd, No. 349 and the 60/847th, No. 289 of JIUYUE in 2006 submission on the 25th submitting on July 20th, 2006.The content of these applications is attached to herein by reference.
Invention field
The micronized sterile solid active pharmaceutical ingredient that the present invention relates to pack, the preparation method of especially aseptic steroid.
Background of invention
Final filling containers is considered to be used to guarantee the best method (sterilization of ＂ terminal point ＂, for example gamma-radiation and thermal cycle) of the minimum risk of microbial contamination as sterilization dosage form or the final packaging device.Yet, solid active ingredient (APIs) substance classes can not be sterilized endways, because all such sterilization technologies influence the quality (for example gamma-radiation and thermal cycle technology often cause the degraded of API, and the thermal cycle in solid suspension can influence polymorphic type and the particle size distribution of suspendible API) of this product.In addition, the preparation (being used for the sterile suspension of parenteral use, the sterile suspension that is used to breathe purposes, imbedibility powder etc.) that comprises solid API can not pass through filtration sterilization, because most of API granule can be retained on the sterilising filter.In addition, the pleomorphic type and the particle size distribution that need closely be controlled in the final dosage form are arranged, because bioavailability and curative effect are therefore influenced by above parameter consumingly.Therefore, use a series of sterilization steps to comprise the filtration and the aseptic method of micronization of sterile solution, exploitation sterile solid API is the preparation method of steroid especially.
International application published WO 99/25359 discloses glucocorticoid, aseptic glucocorticoid and has comprised the sterilization of powder of the sterile preparation of glucocorticoid.Sterilize to about 100 ℃-Yue 130 ℃ by using baking oven or thermal current heating steroid; Yet, may change the crystalline surface character of steroid with this method.
International application published WO 99/25359 also relates to other method that is used for sterilize solid glucocorticosteroid, yet, it claims that these methods are not suitable for the sterilization of steroid or other sensitivity API, because they are to the sensitivity of temperature with owing to the strictness restriction of pharmacopeia about impurity content.
Therefore, the new method that needs exploitation to be used to prepare sterile solid API is arranged.
Summary of the invention
The method of the sterile solid active pharmaceutical ingredient (API) of preparation packing comprises step in glove box or laminar air flow (LAF) cover: the solution of API a) is provided, b) filters this solution; C) precipitation and recovery API from this solution; D) with this API micronization; And e) pack this API, wherein step d) and e at least) in sterile gloves formula control box or LAF cover, carry out.
The accompanying drawing summary
Fig. 1: illustrate aseptic preparation unit.
Fig. 2: illustrate aseptic preparation unit.
Detailed Description Of The Invention
When being used for this paper, the aseptic ＂ of term ＂ refers to there is not microorganism alive fully. Yet, should In fact absolute definition cannot be applied to whole batch, because do not have little life fully in order to confirm Thing, all raw materials of this batch should be cultivated, and each finished product is destroyed fully. Claim to be aseptic Batch sterility therefore use the term about probability to define, wherein unit (unit) or article Contaminated possibility is acceptably few (10-6). The state that such sterility guarantees only With under suitable current good preparation of specification, by the checking and use enough sterilization cycle and Sterilization process is subsequently set up, rather than only depends on the aseptic inspection on limited amount sample Look into. Therefore, sterile unit or item definitions are such unit: wherein based on specific products The statistics relevant with the sterilization situation with the preparation of particular batch is less than 1,000,000/unit Therefore product is exposed to the risk that bacterium is arranged, and (PNSU=has bacterium single namely to find to have the probability of bacterium unit The probability of position) must be lower than 10-6。
The present invention relates to prepare sterile solid API, the high activity API method of glucocorticoid and aseptic powder compounds thereof for example especially, wherein this sterile solid API can be directly used in preparation.This method is not sterilized under the heating and carry out its processing and micronization in laminar air flow (LAF) cover (this paper is also referred to as glove box) or clean room by promptly having at temperate condition, has considered operator's the protection and the protection of product.Because this reason, the operator needn't dress the harm that personal safety equipment is avoided this method, and the aseptic API that obtains by this method has the microbial contamination of lower product and the risk of air degradation.
The example of steroid of the present invention is a triamcinolone, and the typical steroid impurity of this steroid is its 21-aldehyde impurity,
Triamcinolone acetonide triamcinolone acetonide 21-aldehyde
Promptly the impurity that is limited by pharmacopeia forms by steroid and oxygen reaction, and also known this reaction is influenced by heat.In addition, use glove box to replace the clean room,, simplify preparation, keep aseptic condition simultaneously by avoiding making API be transferred to another container from a container opening as in the clean room, carrying out.And this method can easily and effectively be amplified.
The invention provides the method for the micronized sterile solid API of preparation packing in glove box or LAF cover, the method comprising the steps of: sterilize by filtering API solution; Precipitate A PI; Reclaim API, unloading API, and with API micronization and packing, wherein step of unloading and the step of API micronization and packing carried out at least in LAF cover or glove box.Preferably under aseptic condition, filter after the API solution institute in steps, wherein unload at least API with the API micronization and be packaged in glove box or the LAF cover in carry out.
Preferred this method is carried out in Fig. 1 or device shown in Figure 2.With reference now to Fig. 1, embodiment preferred of the present invention is described in detail in detail.
As described in Fig. 1,, in first reactor 1, prepare the solution of API by in suitable solvent, dissolving API.Optional solution can the heating.Filter solution sterilization by filter 2 then, filter 2 is preferably 0.22 micron sterilization cartridge, to eliminate microorganism and other pollutant.Preferred this Filter column is installed in laminar air flow (LAF) cover or the glove box 3.Perhaps or other, the film filter of other type can be used for filtering that (for example filtering table of different size and micron grade (filter disk) or Filter column for example mix nylon 6,6 polymeric films and can derive from the Ultipor of PallCorporation
N66).Preferred solution is not by more than a membrane filtration (setting forth other film filter).
After membrane filtration, in second reactor 4, collect filtrate, wherein by concentrating or cooling off filtrate or pass through both precipitated products.Then precipitate is transferred to Filter dryer 5, wherein removes the impurity that comprises moisture.Preferably filtration product is remained in the Filter dryer 5 to allow further drying, so that can obtain drying solid.Can finish drying by heating, decompression or both, condition is when passing through the heat drying product, also carries out cooling step subsequently.After filtration/drying, the Filter dryer 5 that will comprise desciccate is transferred in LAF cover or the glove box 6.Perhaps, can be in centrifugal dryer filtration product, with product collection in sterile intermediate container 7.In the gnotobasis of LAF cover or glove box 6, remove Filter dryer lid 5B from filtration drying body 5A, so that can unload sterile solid API, be collected in the sterile intermediate container 7.
Then the sterile solid API in the sterile intermediate container 7 is transferred to feeder 8, feeder 8 control API are to the feed rate of micronizer 9, preferred jet mill, in their each comfortable LAF covers or the glove box 11.In micronizer 9, API is pulverized so that the API product of suitable granularity to be provided.The product A PI that will derive from micronizer 9 on weigher 10 weighs, and takes a sample then and is packaged in the sterile chamber 12.Similar device has been described in Fig. 2, wherein the filter among Fig. 1 (post) 2 is replaced by a series of filter (post), be used for filter sterilised with API, wherein Filter dryer 5 does not shift, but with API from the Filter dryer discharging to glove box the intermediate container 7 in 6 the gnotobasis.Then the API in the intermediate container 7 is transferred to aseptic glove box 11, is used for micronization.
Described as Fig. 1 and Fig. 2, device preferably by heat treatment sterilization before using, even Filter dryer stands the sterilization cycle of steam, and is heated to about 122 ℃ with filter and pipeline under vapor stream.After using, with being applicable to the solvent clean filter of removing residue API residue.Select suitable solvent according to API subject to sterilization.In this respect, be used for will device sterilization solvent be the at first dissolved same solvent of API of the micronized sterile solid API that wherein is used to prepare packing.Preferred suitable solvent is mainly polar solvent, and for example alcohol is preferably C
1-C
4The mixture and the water of alcohol, acetone, dimethyl formamide (DMF), DMSO, diox, dimethyl acetylamide, itself and water.Polar organic solvent refers to that polarity index is higher than about 2.0 solvent.
Preferably by in suitable solvent, dissolving API, the solution of preparation API in first reactor.The suitable choice of Solvent of dissolving API depends on the acceptable quality of precipitate and/or crystalline expectation, for example initial particle size distribution (PSD) and polymorphic.The example of suitable solvent is methanol, acetone, dimethyl formamide (DMF), DMSO, diox and dimethyl acetylamide.This step can be carried out under non-sterile condition.The dissolving of API can comprise heating steps.Preferred API is high activity API, and this API is selected from high activity API and the steroid that is used for composition for inhalation.The example that is used for the high activity API of composition for inhalation is tiotropium (Tiotropium) and ciclesonide.Preferred steroids is glucocorticoid such as triamcinolone acetonide, medroxyprogesterone acetate, dexamethasone alkali, budesonide and methylprednisolone acetate.More preferably API is a triamcinolone acetonide.
When API was triamcinolone acetonide, solvent was preferably the mixture of acetone and water.Preferably, carry out triamcinolone acetonide is dissolved in the mixture of acetone and water by being heated to about 35 ℃-Yue 55 ℃, preferred about 40 ℃-Yue 50 ℃ and more preferably from about 45 ℃-Yue 50 ℃; Wherein when handling steroid, be heated to and be lower than 60 ℃ and be considered to safe.
Solution can pass through one or more membrane filtrations, and wherein last is a sterilising filter at least.Filtration is used to eliminate microorganism and other pollutant, can for example carry out in glove box under aseptic condition.Film can be column type, is made by the material compatible with solvent with fluid.Usually carry out three continuous filtration, wherein for the first time be filtered into pre-filtering, be used for protecting being used to the film of sterilizing subsequently.In such filtration subsequently, post can be and comprises the sterilising filtration post that is used for to the tm screen of solution sterilization, for example Ultipor N66 or 0.22 micron sterilization cartridge.The Filter column of other sterilization or film comprise the film of polytetrafluoroethylene (PTFE), preferred Emflon, or comprise film or the filtration grade nylon such as the nylon 6.6 of Kynoar (PVDF).Second can be filter identical or that be different from first prefilter with the 3rd filter (Filter column).Preferably carry out second and filter for the third time subsequently.Preferred second post is made by polytetrafluoroethylene (PTFE) film, preferred Emflon and preferred the 3rd post uses the film preparation of Kynoar (PVDF) or filtration grade nylon such as nylon 6,6, preferred Novasip.When API is triamcinolone acetonide, filters and preferably when keeping the temperature identical, carry out with dissolving step.Yet, when obtaining to dissolve, filter also can not heat and carry out when not heating.
The precipitation of product wherein takes place in the filtrate collection by telolemma or tertiary membrane in second reactor.Can be by being selected from following step induced precipitation: concentrated filtrate, with the combination of anti-solvent dilution filtrate, cooling and these steps.In the method for the invention, precipitation can comprise the crystallization of solid sterile API.The crystallization of such API can be by being added to filtrate carrying out with anti-solvent.Induced precipitation and/or crystalline anti-solvent are preferably water.Can about 60 ℃-Yue 90 ℃, preferably add down anti-solvents, particularly when API is triamcinolone acetonide at about 75 ℃-Yue 85 ℃.Concentrated filtrate in the method for the present invention can be undertaken by the evaporation of solvent.When filtrate is concentrated into precipitation or promotes the precipitation of API, preferably keep the temperature of dissolving step.Preferably, when concentrated filtrate, obtain suspension, and this suspension is cooled to about 0 ℃-Yue 20 ℃, preferred about 10 ℃-Yue 20 ℃, more preferably from about 15 ℃-Yue 20 ℃.When cooling, can stir this suspension.Cooling is enough to make the sedimentary time of API, preferred about 15 minutes-Yue 4 hours time, more preferably from about 30 minutes-Yue 2 hours, most preferably from about 30 minutes.
Sedimentary recovery preferably comprises by Filter dryer or centrifugal dryer, more preferably Filter dryer filters.Filtering product can maintain and be used for further drying in the Filter dryer to obtain drying solid.Be selected from following step dry can comprising: heating, decompression and both combinations.Preferably, heating proceeds to about 30 ℃-Yue 97 ℃.If product also carries out cooling step subsequently by heat drying.Preferably, be cooled to about 20 ℃ from about 97 ℃.Cooling step can carry out a period of time.When API was triamcinolone acetonide, drying means was included in the pressure heating down of reduction.Preferably, heating proceeds to about 85 ℃-Yue 97 ℃, preferred 90 ℃-Yue 97 ℃, more preferably 93 ℃-Yue 97 ℃.Preferably, cooling proceed to about 15 ℃-Yue 35 ℃, preferably to about 20 ℃-Yue 30 ℃.This cooling step can carry out about 6 hours-Yue 24 hours, preferred about 8 hours-Yue 18 hours, more preferably from about 8 hours-Yue 12 hours.
After drying,, and sterile solid API is packaged in the sterile intermediate container the Filter dryer discharging; Wherein the discharging of Filter dryer and raw material are handled in aseptic LAF cover or glove box and are carried out.Preferably, container is sterilized by gamma-radiation or by autoclaving.
The product that obtains from above method is micronization in the sterilized micronizer during being contained in aseptic LAF cover or glove box then.Preferably, the product of acquisition feeds into the micronizer from the intermediate sterile chamber.Micronization process can be by any technology known to those skilled in the art, and for example jet mill apparatus is carried out.
After API was by micronization, it was weighed in sterile chamber, takes a sample and packs.Preferred container is sterilized by gamma-radiation or by autoclaving.
Described the present invention with reference to particularly preferred embodiment and illustrative example, those skilled in the art can recognize and as describing and setting forth the present invention be made amendment, and do not deviate from disclosed spirit and scope of the invention in the description.The disclosure of the list of references of quoting in present patent application in addition, is attached to herein by reference.Propose embodiment and limit its scope by any way to help to understand the present invention but to be not intended to and to should not be considered as.
Embodiment
Embodiment 1: the preparation of sterile solid triamcinolone acetonide:
The triamcinolone acetonide of 1kg is packed in the dissolution reactor, add the acetone of 19.8L and the water of 2.2L then.Suspension is heated to 45 ℃-50 ℃ until dissolving fully and making solution maintain 45 ℃-50 ℃.Solution by three film filters (sterilization cartridge ultipor N66, Filter column Emflon and Filter column Novasip), is transferred to and is applicable to crystallization and sedimentary second reactor.After filtering, use 0.44 apyrogeneity (apirogen) water filter rinsed then with the acetone of 4L.Under vacuum,, keep internal temperature, until the residual volume of residue 3L at about 50 ℃ with the evaporation of the filtrate in second reactor.The suspension that obtains by this way is cooled to 15 ℃-20 ℃, under this temperature, stirred 30 minutes.Then, filtering suspension liquid in Filter dryer cleans solid with the apirogen water of 6L.Under vacuum, Filter dryer remained on then 95 ± 2 ℃ almost 8 hours, subsequently by glove box unloading solid, be packaged in the sterile chamber and transfer to the micronizer apparatus that places glove box in case of necessity.
By to the representative sample of self-desiccation and micronization triamcinolone acetonide batch carries out sterility test and bacterial endotoxin analysis, and monitoring preparation environment closely confirms the microbial quality of this batch.Below form show to support the data that the sterility of preparation batch guarantees.Each batch is aseptic, has the bacterial endotoxin of low content, and the critical environment of preparation meets the A level.
The result of results on sterile triamcinolone
Embodiment 2: the preparation of sterile solid triamcinolone acetonide:
The apirogen water of 29L is packed in the dissolution reactor,, be transferred to and be applicable in sedimentary second reactor by film filter (sterilization cartridge ultipor nylon 66).Heat water to 80 ± 2 ℃.The triamcinolone acetonide of 0.5kg is packed in the dissolution reactor, add the DMF of 2.6L then.Suspension under agitation is heated to 75 ± 5 ℃,, and solution is maintained identical temperature until dissolving fully.Solution by three film filters, is transferred to and is applicable in crystallization and sedimentary second reactor.With the DMF filter rinsed of 1L, and under agitation suspension is kept at 80 ± 2 ℃ and be no less than 1 hour.Then, filtering suspension liquid in Filter dryer, and clean solid twice with the apirogen preheated water (80 ± 2 ℃) of 10L.Under vacuum, Filter dryer was kept 12-24 hour down at 95 ± 2 ℃ then,, be packaged in the sterile chamber and transfer to the micronizer apparatus that places glove box in case of necessity subsequently by glove box unloading solid.Output is about 480 grams.
By to the representative sample of self-desiccation and micronization triamcinolone acetonide batch carries out sterility test and bacterial endotoxin analysis, and monitoring preparation environment closely confirms the microbial quality of this batch.Below form show to support the data that the sterility of preparation batch guarantees.Each batch is aseptic, and has the bacterial endotoxin of low content, and the critical environment of preparation meets the A level.
The result of results on sterile triamcinolone
Embodiment 3: the preparation of production of sterile solid medroxyprogesterone acetate:
The medroxyprogesterone acetate of 1kg is packed in the dissolution reactor, add 2.5L De diox then.Suspension under agitation is heated to 80 ± 5 ℃,, solution is maintained uniform temp until dissolving fully.Solution by film filter (sterilization cartridge ultipor nylon 66), is transferred to and is applicable in crystallization and sedimentary second reactor.With preheating De diox (0.3L, 80 ± 5 ℃) filter rinsed.The apirogen water of 1.3L is packed in the dissolution reactor, and be heated to 80 ± 5 ℃,, be transferred to and be applicable in sedimentary second reactor then by three film filters.After 10 minutes, the apirogen water of 4L is packed in the dissolution reactor, and be heated to 80 ± 5 ℃, and then, be transferred in second reactor by three film filters.Under agitation suspension is kept at 80 ± 5 ℃ and be no less than 1 hour.Then, filtering suspension liquid in Filter dryer cleans solid twice with the apirogen preheated water (80 ± 5 ℃) of 1.5L.Under vacuum, Filter dryer was kept 12-24 hour down at 90 ± 2 ℃ then, subsequently by glove box unloading solid, and be packaged in the sterile chamber, and transfer to the micronizer apparatus that places glove box in case of necessity.Output is about 960 grams.
Embodiment 4: the preparation of production of sterile solid medroxyprogesterone acetate:
The medroxyprogesterone acetate of 1kg is packed in the dissolution reactor, add the DMA of 3L then.Suspension under agitation is heated to 80 ± 5 ℃,, solution is maintained identical temperature until dissolving fully.Solution by film filter (sterilization cartridge ultipor nylon 66), is transferred to and is applicable in crystallization and sedimentary second reactor.DMA (0.3L, 80 ± 5 ℃) filter rinsed with preheating.The apirogen water of 1.2L is packed in the dissolution reactor, and be heated to 80 ± 5 ℃,, be transferred to and be applicable in sedimentary second reactor then by three film filters.After 10 minutes, the apirogen water of 5L is packed in the dissolution reactor, and be heated to 80 ± 5 ℃, and then, be transferred in second reactor by three film filters.Under agitation suspension is kept at 80 ± 5 ℃ and be no less than 1 hour.Then, filtering suspension liquid in Filter dryer, and clean solid twice with the water (80 ± 5 ℃) of the apyrogeneity preheating of 1.5L.Under vacuum, Filter dryer was kept 12-24 hour down at 90 ± 2 ℃ then, subsequently by glove box unloading solid, and be packaged in the sterile chamber, and transfer to the micronizer apparatus that places glove box in case of necessity.
Output is about 960 grams.
Embodiment 5: the preparation of production of sterile solid medroxyprogesterone acetate:
Be applied in identical reagent, solvent, ratio and the temperature reported among the embodiment 3, comprised the precipitation reactor that is used for sedimentary apirogen water but dioxane solution is filtered to.
The output that obtains is identical with the embodiment 3 of previous report.
Embodiment 6: the preparation of production of sterile solid medroxyprogesterone acetate:
Be applied among the embodiment 4 identical reagent, solvent, ratio and the temperature of report, comprised the precipitation reactor that is used for sedimentary apirogen water but DMA solution is filtered to.
The output that obtains is identical with the embodiment 4 of previous report.
Claims (39)
1. the method for the sterile solid active pharmaceutical ingredient (API) that the preparation micronization is packed in laminar air flow (LAF) cover or glove box, described method comprises step:
A) provide the solution of API,
B) described solution is filtered;
C) precipitation and recovery API from described solution;
D) with described API micronization; With
E) pack described API,
Wherein step d) and e at least) in aseptic LAF cover or glove box, carry out.
2. the process of claim 1 wherein step c), d) and e) in LAF cover or glove box, carry out.
3. each method in the aforementioned claim, wherein the institute except that step a) all carries out under aseptic condition in steps.
4. the method for claim 3, wherein said aseptic condition are in aseptic LAF cover or glove box.
5. each method in the aforementioned claim, wherein said API is high activity API and the steroid of the high activity API that is selected from the high activity API that is used for composition for inhalation, is used for parenteral composition.
6. the method for claim 5, the wherein said high activity API that is used for composition for inhalation is tiotropium or ciclesonide.
7. the method for claim 5, wherein said API is a glucocorticoid.
8. the method for claim 7, wherein said glucocorticoid is selected from triamcinolone acetonide, medroxyprogesterone acetate, dexamethasone alkali, budesonide and methylprednisolone acetate.
9. each method in the aforementioned claim, wherein said API solution prepares by described API is dissolved in the solvent.
10. the method for claim 9, wherein said solvent is a polar solvent.
11. the method for claim 10, wherein said solvent are selected from the mixture and the water of alcohol, acetone, dimethyl formamide (DMF), DMSO, diox, dimethyl acetylamide, they and water.
12. the method for claim 11, wherein said API is a triamcinolone acetonide, and described solvent is the mixture of acetone and water.
13. each method among the claim 9-11 wherein with the mixture heated of described API and described solvent, is dissolved in the described solvent described API.
14. the method for claim 13, wherein with the mixture heated of described API and described solvent to about 35 ℃-Yue 55 ℃.
15. the method for claim 13, wherein said API is a triamcinolone acetonide, and by with the mixture heated of acetone and water to about 45 ℃-Yue 50 ℃, it is dissolved in the described mixture.
16. each method in the aforementioned claim, wherein filtration comprises that by one or more membrane filtrations at least one in the described film is bactericidal film.
17. the method for claim 16, wherein said filtration is carried out in LAF cover or glove box.
18. the method for claim 16 or claim 17, wherein said film are selected from polytetrafluoroethylene (PTFE) film, Kynoar (PVDF) film and nylon 6.6 films.
19. each method among the claim 16-18, wherein said filtration comprise at least twice successive filtration.
20. the method for claim 19, wherein said filtration comprise three successive filtrations.
21. the method for claim 20 wherein is filtered into for the first time the pre-filtering that is used to sterilize, be filtered into by the polytetrafluoroethylene (PTFE) film second time, and be filtered into the nylon membrane by Kynoar (PVDF) or filtration grade for the third time.
22. each method among the claim 16-21, wherein said filtration is being undertaken by described API being dissolved under the uniform temp that obtains API solution in the solvent.
23. each method in the aforementioned claim is wherein induced described API precipitation by being selected from following step: concentrated filtrate, anti-solvent is added to filtrate, cooling filtrate and combination thereof.
24. the method for claim 23, wherein said concentration step carries out under the uniform temp that carries out described filtration step.
25. the method for claim 23 or claim 24 wherein makes described API precipitation comprise concentrated filtrate and should spissated filtrate be cooled to about 0 ℃-Yue 20 ℃.
26. the method for claim 25, wherein cooling was carried out about 15 minutes-Yue 4 hours.
27. the method for claim 23, wherein said anti-solvent is a water.
28. the method for claim 27, wherein said API crystallization from filtrate.
29. the method for claim 28, wherein said API is a triamcinolone acetonide, and adds anti-aqueous solvent down at about 60 ℃-Yue 90 ℃.
30. the method for claim 29 wherein adds anti-aqueous solvent down at about 75 ℃-Yue 85 ℃.
31. each method in the aforementioned claim wherein reclaims sedimentary API and comprises by Filter dryer or centrifugal dryer filtration.
32. the method for claim 31 is wherein filtered by Filter dryer, and also is included in the API of dried recovered in the described Filter dryer.
33. the method for claim 32, be selected from following step wherein dry comprising: the API that reclaims is heated, is reduced in pressure and combination thereof in the described Filter dryer.
34. the method for claim 33 wherein is heated to about 30 ℃-Yue 97 ℃.
35. also comprising, the method for claim 34, described method make exsiccant API be cooled to about 15 ℃-Yue 35 ℃.
36. the method for claim 34, wherein said API is a triamcinolone acetonide, and is heated to about 93 ℃-Yue 97 ℃.
37. each method among the claim 32-35, wherein the API of recycling of packaging is included in aseptic LAF cover or the glove box and carries out following step: be packaged in the sterile chamber with described Filter dryer discharging with described sterile solid API.
38. each method in the aforementioned claim, described method is implemented in Fig. 1 or the illustrated device of Fig. 2.
39. the method for claim 37 is wherein at first with described device sterilization.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US83234906P | 2006-07-20 | 2006-07-20 | |
| US60/832,349 | 2006-07-20 | ||
| US60/847,289 | 2006-09-25 |
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| CN101522223A true CN101522223A (en) | 2009-09-02 |
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| Application Number | Title | Priority Date | Filing Date |
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| CNA2007800276024A Pending CN101522223A (en) | 2006-07-20 | 2007-07-20 | Process for the preparation of solid sterile active pharmaceutical ingredient |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103635175A (en) * | 2011-07-06 | 2014-03-12 | 亚碧株式会社 | Sterile refining apparatus for active pharmaceutical ingredients |
| CN108601704A (en) * | 2016-02-05 | 2018-09-28 | 因诺制药有限公司 | Manufacture is used for the stabilization of oxidation-sensitive preparation, instant infusion bag method |
-
2007
- 2007-07-20 CN CNA2007800276024A patent/CN101522223A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103635175A (en) * | 2011-07-06 | 2014-03-12 | 亚碧株式会社 | Sterile refining apparatus for active pharmaceutical ingredients |
| CN108601704A (en) * | 2016-02-05 | 2018-09-28 | 因诺制药有限公司 | Manufacture is used for the stabilization of oxidation-sensitive preparation, instant infusion bag method |
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Application publication date: 20090902 |