WO2021079183A1 - Isopropyl alcohol solvent free crystalline ranitidine hydrochloride form-2 which is free of nitrosamine (ndma) impurity - Google Patents
Isopropyl alcohol solvent free crystalline ranitidine hydrochloride form-2 which is free of nitrosamine (ndma) impurity Download PDFInfo
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- WO2021079183A1 WO2021079183A1 PCT/IB2019/060982 IB2019060982W WO2021079183A1 WO 2021079183 A1 WO2021079183 A1 WO 2021079183A1 IB 2019060982 W IB2019060982 W IB 2019060982W WO 2021079183 A1 WO2021079183 A1 WO 2021079183A1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/52—Radicals substituted by nitrogen atoms not forming part of a nitro radical
Definitions
- the present invention relates to crystalline Ranitidine hydrochloride Form 2 with a residual isopropanol solvent below 100 ppm.
- the present invention particularly relates to crystalline Ranitidine hydrochloride Form 2 with a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method.
- the present invention further relates to an industrial process for the preparation of crystalline Ranitidine hydrochloride Form 2 with a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method.
- Ranitidine hydrochloride is a competitive, reversible inhibitor of the action of histamine at the histamine H2-receptors, including receptors on the gastric cells.
- Ranitidine hydrochloride chemically described as N[2-[[[5-[(dimethylamino)methyl]-2- furanyl]methyl]thio]ethyl]-N'-methyl-2-nitro-l,l-ethenediamine, HC1. It has the following structure:
- the empirical formula is C B H ⁇ N ⁇ S'HCI and the molecular weight is 350.87.
- the above process does not disclose the isopropanol content present in the Form 2 of Ranitidine hydrochloride.
- the inventors of the present invention repeated the same process in the lab and concluded that the process yielding crystalline Form 2 of Ranitidine hydrochloride contains residual isopropanol solvent in the range of 1500-2600 ppm, wherein the solvent content of Isopropanol was find out to be a one of the cause for the presence and rise of the NDMA levels in the pharma.
- NDMA is a nitrosamine known potential impurity which became a focus for the FDA and EMA. This impurity is classified as a probable human carcinogen and is believed to have been introduced into the finished products as a result of the manufacturing process. Due to the presence of NDMA there were lot of recalls happened for Ranitidine HC1 in US and ER The FDA has been working closely with industry to ensure products entering the market do not contain these impurities in the future, whilst establishing suitable analytical methods to determine levels of these impurities and establish interim limits for nitrosamine impurities.
- the inventors of the present invention surprisingly found that the presence of isopropanol solvent content in the Form 2 of Ranitidine hydrochloride causes the rise in the content of NDMA impurity, which may be due to the conversion of isopropanol to isopropyl nitrite which further converted to NDMA impurity.
- the main object of the invention is to provide crystalline Ranitidine hydrochloride Form 2 which contains a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method.
- the present invention provides crystalline Ranitidine hydrochloride Form 2 which contains a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method, wherein the Form 2 is characterized by an X-ray powder diffraction pattern comprising 2Q values in degrees of 8.2, 20.0, 23.3 and 31.7.
- the present invention provides industrial process for the preparation of crystalline Ranitidine hydrochloride Form 2, which contains a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method, wherein the process comprises: a) Dissolving Ranitidine base in methanol, b) Filter the mass of step of a) to get particle free of Ranitidine base, c) Isopropanol HC1 was added to the filtrate of step b), d) Reaction mass was maintained at 30-50°C, e) Dried the material to obtain crystalline Ranitidine hydrochloride Form 2 which contains a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method.
- the present invention provides industrial process for the preparation of crystalline Ranitidine hydrochloride Form 2, which contains a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method, wherein the process comprises: a) Dissolving Ranitidine hydrochloride which contains isopropanol solvent in the range of 1500-2600 ppm in methanol, b) Reaction mass was heated to 40-50°C, c) Reaction mass was cooled to 25-35°, d) Dried the material to obtain crystalline Ranitidine hydrochloride Form 2 which contains a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method.
- FIG. 1 is the X-ray powder diffraction pattern of crystalline Ranitidine hydrochloride Form 2 which contains a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method.
- m i AII I I DESCRIPTION OF TIM IW I NTION
- the present invention provides crystalline Ranitidine hydrochloride Form 2 which contains a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method.
- the solvent content is preferably below 50 ppm.
- the solvent content is preferably below 10 ppm.
- the present invention provides crystalline Ranitidine hydrochloride Form 2 which is substantially free of NDMA.
- crystalline Ranitidine hydrochloride Form 2 contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method. More preferably less than or equal to 0.1 ppm.
- NDMA is a potent carcinogen in experimental animals by several routes of exposure, including through ingestion of drinking-water.
- N-Nitrosodimethylamine, or NDMA can occur from several industrial processes. The following are the general thinking of how NDMA can be formed in the industrial process of any API.
- the present invention provides industrial process for the preparation of crystalline Ranitidine hydrochloride Form 2, which contains a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method, wherein the process comprises: a) Dissolving Ranitidine base in methanol, b) Filter the mass of step of a) to get particle free of Ranitidine base, c) Isopropanol HC1 was added to the filtrate of step b), d) Reaction mass was maintained at 30-50°C, e) Dried the material to obtain crystalline Ranitidine hydrochloride Form 2 which contains a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method.
- the present invention provides industrial process for the preparation of crystalline Ranitidine hydrochloride Form 2, which contains a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method, wherein the process comprises: a) Dissolving Ranitidine hydrochloride which contains isopropanol solvent content in the range of 1500-2600 ppm in methanol, b) Reaction mass was heated to 40-50°C, c) Reaction mass was cooled to 25-35° C, d) Dried the material to obtain crystalline Ranitidine hydrochloride Form 2 which contains a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method.
- the inventors of the present invention have verified that the product obtained using the process described in US 4,521,431 A contains residual isopropanol solvent approximately in the range of 1500-2600 ppm.
- the drying step even though prolonged, does not allow one to reduce the isopropanol content to below several hundred parts per million.
- the product also found to be containing NDMA more than the permitted level.
- Example-1 Preparation of Ranitidine Hydrochloride Form 2 prepared according to the present invention:
- the resulting precipitate was filtered and washed the cake with 38.0mL of excess IPA, allowed for spin dry for 25-35 minutes.
- the filtered solid was dried under vacuum not less than 600 mm/Hg at 50-55°C for 6.0 hours and the obtained material was sieved through 10 meshes. Yield: 92.0 gm.
- Example-2 Procedure for conversion of crystalline Ranitidine Hydrochloride Form 2 containing isopropanol in the range of 1500-2600 ppm to Ranitidine Hydrochloride Form 2 of the present invention
Abstract
The present invention provides crystalline Ranitidine hydrochloride Form 2 with a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than 0.5 ppm as measured by LC-MS/MS method.
Description
ISOPROPYL ALCOHOL SOLVENT FREE CRYSTALLINE RANITIDINE HYDROCHLORIDE FORM-2 WHICH IS FREE OF NITRO S AMINE (NDMA) IMPURITY Mi l l) OF THU TNVUNTTON
The present invention relates to crystalline Ranitidine hydrochloride Form 2 with a residual isopropanol solvent below 100 ppm.
The present invention particularly relates to crystalline Ranitidine hydrochloride Form 2 with a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method.
The present invention further relates to an industrial process for the preparation of crystalline Ranitidine hydrochloride Form 2 with a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method.
BACKGROUND OF THU INVENTION
Ranitidine hydrochloride is a competitive, reversible inhibitor of the action of histamine at the histamine H2-receptors, including receptors on the gastric cells. Ranitidine hydrochloride chemically described as N[2-[[[5-[(dimethylamino)methyl]-2- furanyl]methyl]thio]ethyl]-N'-methyl-2-nitro-l,l-ethenediamine, HC1. It has the following structure:
The empirical formula is CBH^N^S'HCI and the molecular weight is 350.87.
Crystalline Ranitidine hydrochloride Form 2 and its process is first described in US 4,521,431 A, wherein the process comprises dissolving Ranitidine base in isopropanol solvent followed by the addition of concentrated hydrochloric acid. The solution was heated
and seeded with Form 2 of Ranitidine hydrochloride. The Form 2 of Ranitidine hydrochloride product was dried in a vacuum oven at 50°.
The above process does not disclose the isopropanol content present in the Form 2 of Ranitidine hydrochloride. The inventors of the present invention repeated the same process in the lab and concluded that the process yielding crystalline Form 2 of Ranitidine hydrochloride contains residual isopropanol solvent in the range of 1500-2600 ppm, wherein the solvent content of Isopropanol was find out to be a one of the cause for the presence and rise of the NDMA levels in the pharma.
NDMA is a nitrosamine known potential impurity which became a focus for the FDA and EMA. This impurity is classified as a probable human carcinogen and is believed to have been introduced into the finished products as a result of the manufacturing process. Due to the presence of NDMA there were lot of recalls happened for Ranitidine HC1 in US and ER The FDA has been working closely with industry to ensure products entering the market do not contain these impurities in the future, whilst establishing suitable analytical methods to determine levels of these impurities and establish interim limits for nitrosamine impurities.
The inventors of the present invention surprisingly found that the presence of isopropanol solvent content in the Form 2 of Ranitidine hydrochloride causes the rise in the content of NDMA impurity, which may be due to the conversion of isopropanol to isopropyl nitrite which further converted to NDMA impurity.
OBJECT OF THF IW IM ION
The main object of the invention is to provide crystalline Ranitidine hydrochloride Form 2 which contains a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method.
SUMMARY OF THF TNVFNTTON
Accordingly, the present invention provides crystalline Ranitidine hydrochloride Form 2 which contains a residual isopropanol solvent below 100 ppm and contains NDMA
impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method, wherein the Form 2 is characterized by an X-ray powder diffraction pattern comprising 2Q values in degrees of 8.2, 20.0, 23.3 and 31.7.
In a preferred aspect, the present invention provides industrial process for the preparation of crystalline Ranitidine hydrochloride Form 2, which contains a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method, wherein the process comprises: a) Dissolving Ranitidine base in methanol, b) Filter the mass of step of a) to get particle free of Ranitidine base, c) Isopropanol HC1 was added to the filtrate of step b), d) Reaction mass was maintained at 30-50°C, e) Dried the material to obtain crystalline Ranitidine hydrochloride Form 2 which contains a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method.
In another preferred aspect, the present invention provides industrial process for the preparation of crystalline Ranitidine hydrochloride Form 2, which contains a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method, wherein the process comprises: a) Dissolving Ranitidine hydrochloride which contains isopropanol solvent in the range of 1500-2600 ppm in methanol, b) Reaction mass was heated to 40-50°C, c) Reaction mass was cooled to 25-35°, d) Dried the material to obtain crystalline Ranitidine hydrochloride Form 2 which contains a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method.
BRTFF DFSCRTPTTON OF THF DRAWINGS
FIG. 1 is the X-ray powder diffraction pattern of crystalline Ranitidine hydrochloride Form 2 which contains a residual isopropanol solvent below 100 ppm and contains NDMA impurity
less than or equal to 0.5 ppm as measured by LC-MS/MS method. m i AII I I) DESCRIPTION OF TIM IW I NTION
Accordingly, the present invention provides crystalline Ranitidine hydrochloride Form 2 which contains a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method. In a preferred embodiment the solvent content is preferably below 50 ppm. In another preferred embodiment the solvent content is preferably below 10 ppm.
The present invention provides crystalline Ranitidine hydrochloride Form 2 which is substantially free of NDMA. In particular, crystalline Ranitidine hydrochloride Form 2 contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method. More preferably less than or equal to 0.1 ppm.
NDMA is a potent carcinogen in experimental animals by several routes of exposure, including through ingestion of drinking-water. N-Nitrosodimethylamine, or NDMA, can occur from several industrial processes. The following are the general thinking of how NDMA can be formed in the industrial process of any API.
Scheme-T:
Air contamination / Aerial oxidation
In a preferred embodiment, the present invention provides industrial process for the preparation of crystalline Ranitidine hydrochloride Form 2, which contains a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method, wherein the process comprises: a) Dissolving Ranitidine base in methanol, b) Filter the mass of step of a) to get particle free of Ranitidine base, c) Isopropanol HC1 was added to the filtrate of step b), d) Reaction mass was maintained at 30-50°C, e) Dried the material to obtain crystalline Ranitidine hydrochloride Form 2 which contains a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method.
In another preferred embodiment, the present invention provides industrial process for the preparation of crystalline Ranitidine hydrochloride Form 2, which contains a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method, wherein the process comprises: a) Dissolving Ranitidine hydrochloride which contains isopropanol solvent content in the range of 1500-2600 ppm in methanol, b) Reaction mass was heated to 40-50°C,
c) Reaction mass was cooled to 25-35° C, d) Dried the material to obtain crystalline Ranitidine hydrochloride Form 2 which contains a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method.
Due to the carcinogenicity of NDMA and its presence in the final API, it became a big challenge for the industry to prepare Ranitidine HC1 with a permitted control of NDMA. The inventors of the present invention have tried numerous ways to reduce the content of NDMA by optimizing the process and using different crystalline techniques for the enhancement of purity of Ranitidine hydrochloride and surprisingly it has found that the raise in the content of isopropanol solvent also causes a raise in the content of NDMA in the final API.
The inventors of the present invention have verified that the product obtained using the process described in US 4,521,431 A contains residual isopropanol solvent approximately in the range of 1500-2600 ppm. The drying step, even though prolonged, does not allow one to reduce the isopropanol content to below several hundred parts per million. The product also found to be containing NDMA more than the permitted level.
After the research in the lab, the inventors of the present invention found that the reduction in the content of isopropanol leads to the reduction in the NDMA content of the final API. As a part of investigation studies all the possible areas were investigated with systematic approach such as manufacturing process contamination/ Equipment/ Solvents/ Stores contamination etc.,.
At a point of time it has been identified that the crystalline Ranitidine HC1 Form 2 prepared according to the prior art US ‘431 is time being degrading on long standing and generating the NDMA content as reported in the below table (using LCMS/MS), whereas crystalline Ranitidine HC1 Form 2 prepared according to the present invention is stable on long standing and NDMA content is comparatively very less against the crystalline Ranitidine HC1 Form 2 prepared as per the prior art process.
Table-1:
Table 2:
From the above two strategy analysis report we have suspected that isopropyl alcohol is the precursor for formation of NDMA, wherein we suspect that the isopropyl alcohol when exposed to a free Nitrite ion which may available through any of the contamination (Process water/ Aerial) then there will be a chances of formation of Isopropyl nitrite which is active precursor for NDMA with tertiary amine/ secondary amine present in Ranitidine Hydrochloride. After the above results it has been successfully found that NDMA can be avoided in Ranitidine by changing the solvent from isopropanol to methanol or reducing the volumes of isopropanol in the preparation of Ranitidine hydrochloride.
To evident the presence or formation of isopropyl nitrite it has been explored carry over study for isopropyl nitrite for few Ranitidine Hydrochloride batches and it has proven that the formation of Isopropyl nitrite generation.
While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention. The invention is illustrated below with reference to inventive and comparative examples and should not be construed to limit the scope of the invention.
Examples:
Example-1: Preparation of Ranitidine Hydrochloride Form 2 prepared according to the present invention:
In a 500.0 mL RB flask 100.0 gm of Ranitidine base was dissolved in 122.0 mL of Methanol under gentle stirring for 10-15 minutes for complete dissolution of Ranitidine base, the reaction mass was filter through micron filter to get particle free material and further wash the bed with 22.0 mL of Methanol. Take the filtrate mother liquor into a 500.0 mL another clean & dry RB flask, reaction mass pH was adjusted to 4.5-5.5 with IPA.HC1 (66.6 mL) at 25-35°C. The resulting reaction mass was maintained for 90 minutes at 35-40°C to complete formation of salt material. The reaction mass temperature was cooled to 5-10°C under gentle stirring further maintained for 1.0 hour at 5-10°C. The resulting precipitate was
filtered and washed the cake with 38.0mL of excess IPA, allowed for spin dry for 25-35 minutes. The filtered solid was dried under vacuum not less than 600 mm/Hg at 50-55°C for 6.0 hours and the obtained material was sieved through 10 meshes. Yield: 92.0 gm.
Example-2: Procedure for conversion of crystalline Ranitidine Hydrochloride Form 2 containing isopropanol in the range of 1500-2600 ppm to Ranitidine Hydrochloride Form 2 of the present invention
In a 500.0 mL RB flask 100.0 gm of Ranitidine Hydrochloride is taken in 80.0 mL of Methanol and 8.0 mL of Process water under gentle stirring for 10-15 minutes at 25-35°C. Raise the reaction mass temperature to 40-50°C and stir the reaction mass for 30 minutes for complete dissolution of Ranitidine Hydrochloride. After complete dissolution of material reaction mass was allowed to cool down to 25-35°C and filter through micron filter to get particle free and keep aside. Take 300.0 mL of IPA into 500.0 mL RB flask and cool to 8-10°C and slowly add the above particle mass which is kept aside during 15-20 minutes at 8-10°C and stir the reaction mass for 30 minutes to get complete formation of material. After complete formation of material observed, stir the reaction mass for 1.0 hour at below 17-23°C. Further cool the reaction mass temperature to 8-10°C and stir for 30 minutes at 8-10°C and filter the material and wash the cake with 50.0mL of IPA and spin dry the material for 15-20 minutes. The filtered solid was dry under vacuum not less than 600 mm/ Hg at 50-55°C by consistent weight obtained. Yield: 95.0 gm.
Claims
1. Crystalline Ranitidine hydrochloride Form 2 which contains a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method, wherein the Form 2 is characterized by an X-ray powder diffraction pattern comprising 20 values in degrees of 8.2, 20.0, 23.3 and 31.7.
2. Crystalline Ranitidine hydrochloride Form 2 as claimed in claim 1, wherein the Form 2 contains NDMA impurity less than or equal to 0.5 ppm, preferably less than or equal to 0.1 ppm.
3. Industrial process for the preparation of crystalline Ranitidine hydrochloride Form 2, which contains a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method, wherein the process comprises: a) Dissolving Ranitidine base in methanol, b) Filter the mass of step of a) to get particle free of Ranitidine base, c) Isopropanol HC1 was added to the filtrate of step b), d) Reaction mass was heated to 30-50°C, e) Dried the material to obtain crystalline Ranitidine hydrochloride Form 2 which contains a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method.
4. Industrial process for the preparation of crystalline Ranitidine hydrochloride Form 2, which contains a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method, wherein the process comprises: a) Dissolving Ranitidine hydrochloride which contains isopropanol solvent in the range of 1500-2600 ppm in methanol, b) Reaction mass was heated to 40-50°C, c) Reaction mass was cooled to 25-35°, d) Dried the material to obtain crystalline Ranitidine hydrochloride Form 2 which contains a residual isopropanol solvent below 100 ppm and contains NDMA impurity less than or equal to 0.5 ppm as measured by LC-MS/MS method.
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114591274A (en) * | 2022-03-09 | 2022-06-07 | 河北海力香料股份有限公司 | Preparation method of ranitidine hydrochloride |
CN114839288A (en) * | 2022-04-27 | 2022-08-02 | 湖南省药品检验检测研究院 | Method for pretreating ranitidine hydrochloride sample |
Citations (3)
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GB2084580A (en) * | 1980-10-01 | 1982-04-15 | Glaxo Group Ltd | Aminoalkyl Furan Derivative |
US4672133A (en) * | 1980-10-01 | 1987-06-09 | Glaxo Group Limited | Process for forming Form 2 ranitidine hydrochloride |
EP0687174B1 (en) * | 1993-03-05 | 2001-06-13 | Hexal Ag | Crystalline cyclodextrin inclusion complexes of ranitidine hydrochloride and process for their preparation |
-
2019
- 2019-12-18 WO PCT/IB2019/060982 patent/WO2021079183A1/en active Application Filing
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2084580A (en) * | 1980-10-01 | 1982-04-15 | Glaxo Group Ltd | Aminoalkyl Furan Derivative |
US4672133A (en) * | 1980-10-01 | 1987-06-09 | Glaxo Group Limited | Process for forming Form 2 ranitidine hydrochloride |
EP0687174B1 (en) * | 1993-03-05 | 2001-06-13 | Hexal Ag | Crystalline cyclodextrin inclusion complexes of ranitidine hydrochloride and process for their preparation |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114591274A (en) * | 2022-03-09 | 2022-06-07 | 河北海力香料股份有限公司 | Preparation method of ranitidine hydrochloride |
CN114839288A (en) * | 2022-04-27 | 2022-08-02 | 湖南省药品检验检测研究院 | Method for pretreating ranitidine hydrochloride sample |
CN114839288B (en) * | 2022-04-27 | 2023-11-07 | 湖南省药品检验检测研究院 | Pretreatment method of ranitidine hydrochloride Ding Yangpin |
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