WO2015144101A1 - Crystalline and amorphous form of aclidinium chloride and method for their preparation - Google Patents
Crystalline and amorphous form of aclidinium chloride and method for their preparation Download PDFInfo
- Publication number
- WO2015144101A1 WO2015144101A1 PCT/CZ2015/000027 CZ2015000027W WO2015144101A1 WO 2015144101 A1 WO2015144101 A1 WO 2015144101A1 CZ 2015000027 W CZ2015000027 W CZ 2015000027W WO 2015144101 A1 WO2015144101 A1 WO 2015144101A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- chloride
- aclidinium
- crystalline
- formula
- amorphous form
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
Definitions
- the invention relates to new polymorphic forms of aclidinium chloride of structure I and a method of their preparation.
- the invention comprises a new polymorphic form of aclidinium chloride as well as an amorphous form of aclidinium chloride, including methods of their preparation.
- Aclidinium bromide of structure II is the name used for (3R)-3- ⁇ [hydroxy(di-2- thienyl)acetyi]oxy ⁇ -1 -(3-phenoxypropyl)-1 -azoniabicyclo[2,2.2]acetate bromide.
- Aclidinium bromide first described in the patent WO0104118 to Almirall, is a selective antagonist of cholinergic receptors with a long term effect on M 3 receptors. It has significant bronchodilatory effects. It is used for treatment of the chronic obstructive pulmonary disease (COPD).
- COPD chronic obstructive pulmonary disease
- the therapeutic dosage of the active substance is low (400 pg), in the form of powder, which is applied with the use of an inhalation aid.
- Aclidinium bromide is a promising successor of tiotropium bromide as with the same bronchodilatory effect is exhibits fewer side effects (Cazzola M., Page C. P., Matera M. G., Expert Opin. Pharmacother. 2013 14(9), 1205-1214)).
- Aclidinium refers to the free ammonium cation (structure III), in the patent WO0104118 the anions bromide, chloride and trifluoroacetate are claimed for this aclidinium cation.
- the examples only describe the preparation of aclidinium bromide. The application does not mention a preparation method or crystalline form of aclidinium chloride or trifluoroacetate.
- the invention relates to new forms of aciidinium chloride of formula I and a method of their preparation.
- the forms provided by the present invention exhibit excellent physical-chemical characteristics suitable especially for the preparation of the dosage form - for filling into an inhalation aid in the form of micronized powder with the required particle size.
- aciidinium represents a very important part of pharmaceutical development as a higher number of pharmaceutically acceptable salts and forms naturally significantly increases the chance of obtaining a stable, pharmaceutically acceptable substance, complying with the formulation demands.
- the use of aciidinium in inhalation devices is preceded by grinding (micronization) of the substance to the required particle size (1-5 pm). Micronization may represent a substantial intervention into the given crystalline form of the pharmaceutical product (change to the amorphous form or a less suitable/stable crystalline modification). For this reason, as many stable forms and salts of a particular pharmaceutical substance - in this case aciidinium - as possible should be available.
- aciidinium chloride and its crystalline modification in accordance with this invention appear to be an ideal candidate for use in pharmaceutical formulation. Its main advantage is that in micronization, which is necessary to achieve the required particle size, it does not undergo amorphization or transition to another crystalline form.
- This invention provides a crystalline aclidinium chloride, both in an anhydrous or hyd rated (water containing) form and in an unsolvated or solvated form.
- the new crystalline form of aclidinium chloride of chemical formula 1 prepared in accordance with this invention is referred to as Form A and it manifests the following characteristic reflections in the X-ray powder pattern measured with the use of CuKa radiation: 7.8; 10.5; 13.2; 17.2; 19.2; 21.8 and 26.1 + 0.2° 2-theta.
- the X-ray pattern of Form A is shown in Figure 1.
- amorphous form of aclidinium chloride of formula I which is characterized by the X-ray pattern shown in Figure 2.
- processes for producing the above mentioned forms of aclidinium chloride are aiso provided.
- the crystalline Form A of aclidinium chloride was prepared by a reaction of the quinuclidinyl ester V with 3-phenoxy propyl chloride in a suitable solvent (Scheme 1).
- acetonitrile is used for this reaction.
- An excess of the alkylation agent is used for the reaction, namely in an amount of 2 to 6 equivalents; in a preferred embodiment 4 equivalents are used.
- the reaction is carried out at the temperatures of 25°C to the boiling point of the solvent and pressures of 101.325 kPa to 210 kPa. In a convenient embodiment the reaction is carried out at 100-106°C (the reaction mixture is heated up to this temperature).
- the reaction time is 4 to 100 hours, in a preferred embodiment the reaction is carried out for less than 24 hours.
- the amorphous form of aclidinium chloride was prepared from the crystalline Form A by !yophilization of a frozen solution of aclidinium chloride in a suitable solvent or mixture of solvents.
- suitable solvents include water or mixtures of water and an alcohol.
- terf-Butanol can be used as a suitable alcohol. In a preferred embodiment a mixture of water and ferf-butanol in the proportion of 6:4 is used.
- the samples were characterized and specified by the X-ray method and by their melting point. Chemical purity was determined with the use of liquid chromatography (UPLC). The quantities of solvents were determined with the use of gas chromatography (GC). The lyophilization was done in the Christ, ALPHA 2- 4 LSC device.
- 3-Phenoxypropyl chloride was prepared by reaction of 1-bromo-3-chloropropane with phenol in basic conditions in accordance with an example of the patent WO2012062918 and purified by vacuum distillation.
- Mobile phase A: 2 ml of 70% perchloric acid R are dissolved in 1000 ml of water for the chromatography R.
- Capillary column CP-Sii 5CB (30 m x 0.32 mm x 3.0 pm) or equivalent Temperature program 40°C - 0 min, at 15°C /min to 90°C - 0 min, at 30°C /min to
- Carrier gas helium for chromatography R; 2.2 ml/min
- 0.02 rad Soller slits 0.02 rad Soller slits, a 10mm mask and a 1/4° fixed anti-dispersion slit were used for the correction of the primary array.
- the irradiated area of the sample is 10 mm, programmable divergence slits were used.
- 0.02 rad Soller slits and a 5.0 anti-dispersion slit were used.
- Fig. 1 X-ray powder pattern of Form A of aclidinium chloride
- Example 1 The quinuclidinyl ester V (166 mg, 0.475 mmol, purity 99.95%) was charged into a pressure flask (a heavy-walled flask of borosilicate glass) and suspended in acetonitrile (7 mi). 3-phenoxypropyl chloride (0.3 ml, 1.9 mmoi, 4 equivalents) was added dropwise to the agitated suspension at 25°C and the flask was closed with a Teflon screw plug with a seal. The reaction mixture was subsequently heated up to 105°C and stirred at this temperature for 19 hours.
- the quinuclidinyl ester V (1 ,5 mg, 4.29 mmol, purity 99.95%) was charged into a pressure flask (a heavy-walled flask of borosilicate glass) and suspended in acetonitrile (30 ml). 3-Phenoxypropyl chloride (2.7 ml, 17.16 mmol, 4 equivalents) was added dropwise to the agitated suspension at 25°C and the flask was closed with a Teflon screw plug with a seal. The reaction mixture was subsequently heated up to 105.5°C and stirred at this temperature for 111 hours.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
New forms of aclidinium chloride of formula I. The process for preparing the crystalline aclidinium chloride consists in reaction of the quinuclidinyl ester of formula V with 3-phenoxypropyl chloride in acetonitrile.
Description
CRYSTALLINE AND AMORPHOUS FORM OF ACLIDINIUM CHLORIDE AND METHOD FOR THEIR PREPARATION
Technical Field
The invention relates to new polymorphic forms of aclidinium chloride of structure I and a method of their preparation. The invention comprises a new polymorphic form of aclidinium chloride as well as an amorphous form of aclidinium chloride, including methods of their preparation.
Aclidinium Chloride
Background Art
Aclidinium bromide of structure II is the name used for (3R)-3-{[hydroxy(di-2- thienyl)acetyi]oxy}-1 -(3-phenoxypropyl)-1 -azoniabicyclo[2,2.2]acetate bromide.
Aclidinium bromide, first described in the patent WO0104118 to Almirall, is a selective antagonist of cholinergic receptors with a long term effect on M3 receptors. It has significant bronchodilatory effects. It is used for treatment of the chronic obstructive pulmonary disease (COPD). The therapeutic dosage of the active substance is low (400 pg), in the form of powder, which is applied with the use of an inhalation aid. Aclidinium bromide is a promising successor of tiotropium bromide as with the same bronchodilatory effect is exhibits fewer side effects (Cazzola M., Page C. P., Matera M. G., Expert Opin. Pharmacother. 2013 14(9), 1205-1214)).
II
Aclidinium Bromide
A preparation process of aclidinium bromide was first described in the patent WO0104118, later also in the process patent WO2008009397.
Aclidinium refers to the free ammonium cation (structure III), in the patent WO0104118 the anions bromide, chloride and trifluoroacetate are claimed for this aclidinium cation. However, the examples only describe the preparation of aclidinium bromide. The application does not mention a preparation method or crystalline form of aclidinium chloride or trifluoroacetate.
III
Aclidinium
The patent application WO2005097126 (also WO20005014044, WO2006015970, WO2006079625 and WO2006094924) claims other aclidinium salts (fluoride, chloride, bromide, iodide, sulfate, phosphate, methanesulfonate, nitrate, maieate, acetate, citrate, fumarate, tartrate, oxalate, succinate, benzoate and p- toluenesulfonate), possibly occurring in a racemate, enantiomer or hydrate form. However, none of the above mentioned documents contains preparation methods,
physical-chemical characteristics or characteristics of the solid forms themselves of the above mentioned aciidinium salts.
Disclosure of Invention
The invention relates to new forms of aciidinium chloride of formula I and a method of their preparation.
Aciidinium Chloride The forms provided by the present invention exhibit excellent physical-chemical characteristics suitable especially for the preparation of the dosage form - for filling into an inhalation aid in the form of micronized powder with the required particle size.
Preparation of new forms and salts of aciidinium represents a very important part of pharmaceutical development as a higher number of pharmaceutically acceptable salts and forms naturally significantly increases the chance of obtaining a stable, pharmaceutically acceptable substance, complying with the formulation demands. The use of aciidinium in inhalation devices is preceded by grinding (micronization) of the substance to the required particle size (1-5 pm). Micronization may represent a substantial intervention into the given crystalline form of the pharmaceutical product (change to the amorphous form or a less suitable/stable crystalline modification). For this reason, as many stable forms and salts of a particular pharmaceutical substance - in this case aciidinium - as possible should be available. It has been surprisingly found out that aciidinium chloride and its crystalline modification in accordance with this invention appear to be an ideal candidate for use in pharmaceutical formulation. Its main advantage is that in micronization, which is necessary to achieve the required
particle size, it does not undergo amorphization or transition to another crystalline form.
This invention provides a crystalline aclidinium chloride, both in an anhydrous or hyd rated (water containing) form and in an unsolvated or solvated form.
The new crystalline form of aclidinium chloride of chemical formula 1 prepared in accordance with this invention is referred to as Form A and it manifests the following characteristic reflections in the X-ray powder pattern measured with the use of CuKa radiation: 7.8; 10.5; 13.2; 17.2; 19.2; 21.8 and 26.1 + 0.2° 2-theta. The X-ray pattern of Form A is shown in Figure 1.
According to another aspect of this invention, there is provided amorphous form of aclidinium chloride of formula I, which is characterized by the X-ray pattern shown in Figure 2. There are aiso provided processes for producing the above mentioned forms of aclidinium chloride.
The crystalline Form A of aclidinium chloride was prepared by a reaction of the quinuclidinyl ester V with 3-phenoxy propyl chloride in a suitable solvent (Scheme 1). In a preferred embodiment acetonitrile is used for this reaction. An excess of the alkylation agent is used for the reaction, namely in an amount of 2 to 6 equivalents; in a preferred embodiment 4 equivalents are used. The reaction is carried out at the temperatures of 25°C to the boiling point of the solvent and pressures of 101.325 kPa to 210 kPa. In a convenient embodiment the reaction is carried out at 100-106°C (the reaction mixture is heated up to this temperature). The reaction time is 4 to 100 hours, in a preferred embodiment the reaction is carried out for less than 24 hours.
Scheme 1
I
Aclidinium Chloride
The amorphous form of aclidinium chloride was prepared from the crystalline Form A by !yophilization of a frozen solution of aclidinium chloride in a suitable solvent or mixture of solvents. Suitable solvents include water or mixtures of water and an alcohol. terf-Butanol can be used as a suitable alcohol. In a preferred embodiment a mixture of water and ferf-butanol in the proportion of 6:4 is used.
Measurement methods
In the examples below, the samples were characterized and specified by the X-ray method and by their melting point. Chemical purity was determined with the use of liquid chromatography (UPLC). The quantities of solvents were determined with the use of gas chromatography (GC). The lyophilization was done in the Christ, ALPHA 2- 4 LSC device.
3-Phenoxypropyl chloride was prepared by reaction of 1-bromo-3-chloropropane with phenol in basic conditions in accordance with an example of the patent WO2012062918 and purified by vacuum distillation.
The melting points were measured with the BUCHI Melting Point B-514 device. Purity analysis method:
Liquid chromatography is carried out (Ph.Eur. 2.2.29):
Chromatographic conditions:
Instrument: UPLC system with a UV/VIS or PDA detector
Chemicals: acetonitriie R1
water for the chromatography R
perchloric acid 70% R
Column:
- dimensions: length = 100 mm, inner diameter = 4.6 mm
- stationary phase: XSelect CSH Phenyi-Hexyl 2.5 μηι
- temperature: 35°C
Mobile phase: A: 2 ml of 70% perchloric acid R are dissolved in 1000 ml of water for the chromatography R.
B: acetonitrile R1
elution gradient
flow rate: 0.7 ml/min
injected quantity: 1.0 μΙ
Sample temperature: 18°C
Detection: UV, 220 nm
time: 15.0 min
Determination of residual solvents (gas chromatography - GC)
The following solvents are monitored: Acetonitrile
Gas chromatography (2.2.28) is carried out with headspace injection and Fl detection:
Capillary column: CP-Sii 5CB (30 m x 0.32 mm x 3.0 pm) or equivalent Temperature program 40°C - 0 min, at 15°C /min to 90°C - 0 min, at 30°C /min to
160°C - 0 min
Carrier gas: helium for chromatography R; 2.2 ml/min
Injector: splitting flow 4.4 ml/min, 165 °C
Detector: FID, 300°C, Range: 1 , Attn: -4
Measurement parameters of the X-ray powder diffraction: The diffraction patterns were obtained using an XPERT PRO MPD PANalytical powder diffractometer, radiation used: CuKct (λ=1.542 A), excitation voltage: 45 kV, anode current: 40 mA, measured range: 2 - 40° 2Θ, increment: 0.01 ° 2Θ at the dwell time at a reflection of 0.5 s, the measurement was carried out with a flat sample with the area/thickness of 10/0.5 mm. 0.02 rad Soller slits, a 10mm mask and a 1/4° fixed anti-dispersion slit were used for the correction of the primary array. The irradiated area of the sample is 10 mm, programmable divergence slits were used. For the correction of the secondary array 0.02 rad Soller slits and a 5.0 anti-dispersion slit were used.
Brief Description of Drawings
Fig. 1. X-ray powder pattern of Form A of aclidinium chloride
Fig. 2. X-ray powder pattern of the amorphous form of aclidinium chloride
Examples
Preparation of the polymorphic Form A of aclidinium chloride by direct synthesis
Example 1 The quinuclidinyl ester V (166 mg, 0.475 mmol, purity 99.95%) was charged into a pressure flask (a heavy-walled flask of borosilicate glass) and suspended in acetonitrile (7 mi). 3-phenoxypropyl chloride (0.3 ml, 1.9 mmoi, 4 equivalents) was added dropwise to the agitated suspension at 25°C and the flask was closed with a Teflon screw plug with a seal. The reaction mixture was subsequently heated up to 105°C and stirred at this temperature for 19 hours. Then, the reaction mixture was cooled down to 25°C and less, the crystalline product was filtered, washed with acetonitrile (25 ml) and dried in a stream of nitrogen at the temperature of 25°C and the pressure of 101.325 kPa. Aclidinium chloride Form A was obtained in the form of white crystals ( 56 mg, yield 63% by weight). Melting point 229.9 to 232.1°C. Product
purity 99.77% (UPLC). Residual solvents/reactants - acetonitrile (determined by GC) 0.04%; 3-phenoxypropyl chloride (determined by GC) 0.009%. The X-ray powder pattern is shown in annexed Fig. 1.
X-ray powder diffraction - Diffraction peaks of form A of aclidinium chloride
Pos. [°2Th.] d-spacing [A] Rel. Int. [%]
7.75 11.397 78.9
8.12 10.882 6.1
10.47 8.439 59.3
12.04 7.345 54.3
13.24 6.682 100.0
13.86 6.387 17.3
14.54 6.088 5.8
15.55 5.693 15.9
16.29 5.439 31.3
16.65 5.320 23.8
17.15 5.166 41.5
17.59 5.037 6.7
18.56 4.778 12.9
19.18 4.624 49.3
20.19 4.394 17.8
20.71 4.286 30.1
21.05 4.217 15.8
21.48 4.133 24.5
21.79 4.076 61.8
22.36 3.973 14.2
22.78 3.901 12.7
23.38 3.802 26.0
23.76 3.741 19.6
24.54 3.624 28.2
25.58 3.479 19.8
26.05 3.418 38.7
26.46 3.366 15.5
27.21 3.275 6.2
27.79 3.208 8.5
28.86 3.092 8.0
29.40 3.036 7.9
29.65 3.010 17.2
31.20 2.864 10.7
31.73 2.818 4.6
32.98 2.714 5.5
33.94 2.640 7.1
34.75 2.579 12.1
I 38.92 2.312 5.5
Example 2
The quinuclidinyl ester V (1 ,5 mg, 4.29 mmol, purity 99.95%) was charged into a pressure flask (a heavy-walled flask of borosilicate glass) and suspended in acetonitrile (30 ml). 3-Phenoxypropyl chloride (2.7 ml, 17.16 mmol, 4 equivalents) was added dropwise to the agitated suspension at 25°C and the flask was closed with a Teflon screw plug with a seal. The reaction mixture was subsequently heated up to 105.5°C and stirred at this temperature for 111 hours. Then, the reaction mixture was cooled down to 25°C and less, the crystalline product was filtered through frit, washed with 00 ml of acetonitrile and dried in a stream of nitrogen at the temperature of 25°C and the pressure of 101.325 kPa. Aclidinium chloride Form A was obtained in the form of white crystals (2.09 g, yield 94% by weight). Melting point 229.5 to 230.5°C. Product purity 99.97%. The X-ray powder pattern was identical to the X-ray powder pattern of Example 1.
Preparation of the amorphous form of aclidinium chloride Example 3
Aclidinium chloride (0.25 g, 0.481 mmol, Form A) was dissolved in a mixture of water : ie/f-butanol=6:4 (150 ml altogether) at 25°C. The clear solution was frozen (a bath with a mixture of dry ice and ethanol, -70°C) and lyophilized (vacuum: 1.8 Pa for 20h). The amorphous form of aclidinium chloride (0.25 g) was obtained. Melting point 224.0 to 224.3°C. The X-ray powder diffraction confirmed the amorphous form. The X-ray powder pattern is shown in annexed Fig. 2.
Example 4
Aclidinium chloride (0.20 g, 0.385 mmol, Form A) was dissolved in a mixture of water : ferf-butanol=6:4 (150 mi altogether) at 25°C. The clear solution was frozen (a bath with a mixture of dry ice and ethanoi, -70°C) and subjected to lyophiiization (vacuum-. 1.8 Pa for 20h). The amorphous aclidinium chloride (0.20 g) was obtained. Melting point: 224.2 to 224.4°C. The X-ray powder diffraction confirmed the amorphous form. The X-ray powder pattern was identical to the X-ray powder pattern of Example 3.
Claims
Cfaims
1) Crystalline aclidinium chloride of formula I.
0)
2) The crystalline aclidinium chloride of formula I, Form A according to claim 1 , characterized in that it exhibits the following characteristic peaks in the X-ray pattern measured with the use of CuKa radiation: 7.8; 10.5; 13.2; 17.2; 19.2; 21.8 and 26.1±0.2°2-theta.
3) A process for preparing the crystalline aclidinium chloride as defined in claims 1 and 2, characterized in that quinuclidinyl ester of formula V is reacted with 3- phenoxypropyl chloride in acetonitrile.
4) The process according to claim 3, characterized in that an excess of 3- phenoxypropyl chloride is used for the reaction in an amount of 2 to 6 equivalents, preferably of 4 equivalents.
5) The process according to claims 3 or 4, characterized in that the reaction is carried out at a temperature of from 25°C to the boiling point of the solvent and a pressure of 101.325 kPa to 210 kPa, preferably at 100 to 106°C.
6) The process according to claims 3 to 5, characterized in that the reaction time is 4 to 100 hours, preferably less than 24 hours.
7) An amorphous aclidinium chloride of formula I.
8) A process for preparing the amorphous form of aclidinium chloride as defined in claim 7, characterized in that the amorphous form is prepared by lyophilization of a frozen solution of aclidinium chloride in a suitable solvent.
9) The process according to claim 8, characterized in that the solvent is water or a mixture of water and an alcohol, preferably a mixture of water and te/f-butanol in the proportion of 6:4.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CZPV2014-188 | 2014-03-26 | ||
| CZ2014-188A CZ2014188A3 (en) | 2014-03-26 | 2014-03-26 | Novel forms of aclidinium chloride and process for preparing thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2015144101A1 true WO2015144101A1 (en) | 2015-10-01 |
Family
ID=52828936
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CZ2015/000027 WO2015144101A1 (en) | 2014-03-26 | 2015-03-26 | Crystalline and amorphous form of aclidinium chloride and method for their preparation |
Country Status (2)
| Country | Link |
|---|---|
| CZ (1) | CZ2014188A3 (en) |
| WO (1) | WO2015144101A1 (en) |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001004118A2 (en) | 1999-07-14 | 2001-01-18 | Almirall Prodesfarma S.A. | Quinuclidine derivatives and their use as muscarinic m3 receptor ligands |
| WO2005014044A1 (en) | 2003-07-29 | 2005-02-17 | Boehringer Ingelheim International Gmbh | Medicaments for inhalation comprising betamimetics and an anticholinergic |
| WO2005097126A1 (en) | 2004-03-30 | 2005-10-20 | Boehringer Ingelheim International Gmbh | Compounds for treating proliferative processes |
| US20050239778A1 (en) * | 2004-04-22 | 2005-10-27 | Boehringer Ingelheim International Gmbh | Novel medicament combinations for the treatment of respiratory diseases |
| WO2006015970A2 (en) | 2004-08-13 | 2006-02-16 | Boehringer Ingelheim International Gmbh | Medicaments for the prevention or treatment of alveolar pneumonia comprising an anticholinergic |
| WO2006079625A2 (en) | 2005-01-28 | 2006-08-03 | Boehringer Ingelheim International Gmbh | Medicaments for the prevention or treatment of heart failure comprising administration of an anticholinergic |
| WO2006094924A2 (en) | 2005-03-09 | 2006-09-14 | Boehringer Ingelheim International Gmbh | New pharmaceutical compositions based on anticholinergics and pde 5-inhibitors |
| WO2008009397A1 (en) | 2006-07-21 | 2008-01-24 | Laboratorios Almirall, S.A. | Process for manufacturing 3(r)-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide |
| WO2012062918A1 (en) | 2010-11-12 | 2012-05-18 | Lek Pharmaceuticals D.D. | Process for the preparation of 3-aroyl-5-aminobenzofuran derivatives |
-
2014
- 2014-03-26 CZ CZ2014-188A patent/CZ2014188A3/en unknown
-
2015
- 2015-03-26 WO PCT/CZ2015/000027 patent/WO2015144101A1/en active Application Filing
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001004118A2 (en) | 1999-07-14 | 2001-01-18 | Almirall Prodesfarma S.A. | Quinuclidine derivatives and their use as muscarinic m3 receptor ligands |
| WO2005014044A1 (en) | 2003-07-29 | 2005-02-17 | Boehringer Ingelheim International Gmbh | Medicaments for inhalation comprising betamimetics and an anticholinergic |
| WO2005097126A1 (en) | 2004-03-30 | 2005-10-20 | Boehringer Ingelheim International Gmbh | Compounds for treating proliferative processes |
| US20050239778A1 (en) * | 2004-04-22 | 2005-10-27 | Boehringer Ingelheim International Gmbh | Novel medicament combinations for the treatment of respiratory diseases |
| WO2006015970A2 (en) | 2004-08-13 | 2006-02-16 | Boehringer Ingelheim International Gmbh | Medicaments for the prevention or treatment of alveolar pneumonia comprising an anticholinergic |
| WO2006079625A2 (en) | 2005-01-28 | 2006-08-03 | Boehringer Ingelheim International Gmbh | Medicaments for the prevention or treatment of heart failure comprising administration of an anticholinergic |
| WO2006094924A2 (en) | 2005-03-09 | 2006-09-14 | Boehringer Ingelheim International Gmbh | New pharmaceutical compositions based on anticholinergics and pde 5-inhibitors |
| WO2008009397A1 (en) | 2006-07-21 | 2008-01-24 | Laboratorios Almirall, S.A. | Process for manufacturing 3(r)-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide |
| WO2012062918A1 (en) | 2010-11-12 | 2012-05-18 | Lek Pharmaceuticals D.D. | Process for the preparation of 3-aroyl-5-aminobenzofuran derivatives |
Non-Patent Citations (4)
| Title |
|---|
| CAZZOLA M.; PAGE C. P.; MATERA M. G., EXPERT OPIN. PHARMACOTHER., vol. 14, no. 9, 2013, pages 1205 - 1214 |
| CAZZOLA, M. ET AL.: "Aclidinium bromide for the treatment of chronic obstructive pulmonary disease", EXPERT OPINION ON PHARMACOTHERAPY, vol. 14, no. 9, 2013, pages 1205 - 1214, XP009185072, ISSN: 1465-6566, DOI: 10.1517/14656566.2013.789021 * |
| HATLEY, R.H.M. ET AL.: "Stabilization of a pharmaceutical drug substance by freeze-drying: A case study", DRUG STABILITY, vol. 1, no. 2, 1996, pages 73 - 85, XP009087829, ISSN: 1355-5618 * |
| TANG, X.C. ET AL.: "Design of Freeze-Drying Processes for Pharmaceuticals: Practical Advice", PHARMACEUTICAL RESEARCH, vol. 21, no. 2, 2004, pages 191 - 200, XP008124987, ISSN: 0724-8741 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CZ2014188A3 (en) | 2015-10-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20230242515A1 (en) | Crystalline form of 6-(cyclopropanecarboxamido)-4-((2-methoxy-3-(1-methyl-1h-1,2,4-triazol-3-yl)phenyl)amino)-n-(methyl-d3) pyridazine-3-carboxamide | |
| CN113527203B (en) | Crystal form of lenvatinib mesylate as well as preparation method and application thereof | |
| CN110049980B (en) | Salt of opioid receptor (MOR) agonist, fumarate I crystal form of salt and preparation method of fumarate I crystal form | |
| JP6916207B2 (en) | Synthesis of indazole | |
| DK2547649T3 (en) | Agomelatine Hydrochloride Hydrate and its Preparation | |
| CN111995582B (en) | Eutectic of olaparib and urea and preparation method thereof | |
| CN105111215A (en) | Crystal form and preparation method of cyclin-dependent kinase inhibitor | |
| CN108727347B (en) | Crystal form of opioid receptor (MOR) agonist and preparation method thereof | |
| KR20220161368A (en) | Preparation of MCL-1 inhibitory compounds by methylation in the presence of water | |
| WO2015062560A1 (en) | An industrially applicable process for preparing high purity aclidinium bromide | |
| WO2015144101A1 (en) | Crystalline and amorphous form of aclidinium chloride and method for their preparation | |
| WO2016119742A1 (en) | (3β)-17-(1h-benzimidazole-1-yl)androstane-5, and 16-diene-3-ol salts and preparation methods therefor | |
| WO2020025449A1 (en) | Highly stable crystalline eltrombopag monoethanolamine salt form d1 | |
| EP2831068A1 (en) | A method of preparing the scopine ester of di-(2-thienyl)glycolic acid, an intermediate in the synthesis of tiotropium bromide | |
| JP2015521179A (en) | Agomelatine acid group composite and its production method and use | |
| UA105424C2 (en) | Agomelatine hydrobromide hydrate and preparation thereof | |
| CN108137626B (en) | Crystalline forms of Fosnetupitant | |
| Rotival et al. | Comprehensive determination of the solid state stability of bethanechol chloride active pharmaceutical ingredient using combined analytical tools | |
| TWI680977B (en) | Polymorphic forms and co-crystals of a c-met inhibitor | |
| WO2013107434A2 (en) | New polymorphous forms of tiotropium iodide and a method of their preparation | |
| CN117003702B (en) | Fluocytosine-orotate and preparation method and application thereof | |
| CN110857302A (en) | Preparation method of sitagliptin hydrochloride monohydrate crystal form | |
| WO2024109727A1 (en) | Crystalline form of pharmaceutically acceptable salt of pyrazolo heteroaryl derivative | |
| Ryu et al. | Solid state of a new PDE-5 inhibitor DA-8159: Characterization, dissolution, transformation | |
| JP2018531249A6 (en) | Crystalline form of Phosnetupitant |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 15715962 Country of ref document: EP Kind code of ref document: A1 |
|
| NENP | Non-entry into the national phase | ||
| 122 | Ep: pct application non-entry in european phase |
Ref document number: 15715962 Country of ref document: EP Kind code of ref document: A1 |