- Isomorphism, disorder, and hydration in the crystal structures of racemic and single-enantiomer carvedilol phosphate
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Understanding the crystalline structure of racemic carvedilol phosphate hemihydrate presents several challenges that were overcome using a combination of single-crystal X-ray diffraction, solid-state NMR (SSNMR), and other analytical techniques. Initial attempts to obtain a crystal structure were hampered by difficulties with twinning and problematic disorder in the final refinements. Multinuclear SSNMR analysis localized the disorder to portions of the molecule near the chiral center. As a result, single-enantiomer carvedilol phosphate was prepared and was found to crystallize in a phase that was isomorphous with the racemate, while SSNMR spectra of the single enantiomers did not contain the disorder observed in the racemate. The single-crystal X-ray structure of the (R)-enantiomer was solved and used as a starting point to successfully progress the solution of the disordered racemic crystal structure. Thermal analysis and construction of a phase diagram, along with crystallographic and spectroscopic analysis, found the crystal structure of the racemate to be a solid solution of (R)- and (S)-enantiomers, with the conformation of the molecule adjusting to fit. The crystal structures show the stoichiometry of the both the racemate and (R)-enantiomer to be a hemihydrate. The phase isomorphically dehydrates below relative humidity values of 1% and above temperatures of 125 °C as assessed by water vapor sorption studies, powder X-ray diffraction, and SSNMR. Single-crystal diffraction detected significant changes in the unit cell dimensions as the phase dehydrated, which was related to the visual appearance of opacity in a single crystal of the (R)-enantiomer. The mechanism of water incorporation was further probed spectroscopically via exchange with deuterium, 17O-, and 18O-labeled water; the results suggest that dehydration and rehydration likely proceed via narrow tunnels in the crystal structure, combined with the formation of fissures in the crystal. 2H SSNMR experiments showed that the water does not engage in solid-state jump motion even at higher temperatures.
- Vogt, Frederick G.,Copley, Royston C. B.,Mueller, Ronald L.,Spoors, Grant P.,Cacchio, Thomas N.,Carlton, Robert A.,Katrincic, Lee M.,Kennady, James M.,Parsons, Simon,Chetina, Olga V.
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- Preparation method of carvedilol phosphate hemihydrate
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The invention provides a preparation method of carvedilol phosphate hemihydrates. The preparation method comprises the following steps: carrying out mixing reaction on a compound with a structure as shown in a formula (II) and 2-(2-methoxy phenoxy) ethylamine to obtain reaction liquid containing a compound with the structure as shown in a formula (III); directly adding phosphoric acid in the reaction liquid obtained in the step (1) so that 2-(2-methoxy phenoxy) ethylamine phosphate and filtrate can be obtained; adding phosphoric acid in the filtrate obtained in the step (2) to obtain the carvedilol phosphate hemihydrates. The reaction liquid obtained in the step (1) is not required to be treated, the phosphoric acid is added in the same reaction system in two steps, excessive 2-(2-methoxy phenoxy) ethylamine is recycled and can be continued to be used for reaction, and furthermore, the purity and the yield of the prepared carvedilol phosphate hemihydrates as a target product are quite high. In addition, preparation of the compound with the structure as shown in the formula (II) and the carvedilol phosphate hemihydrate as the target product is realized through a one-pot method, and a synthesis method is simple.
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- CONTROLLED-RELEASE FLOATING PHARMACEUTICAL COMPOSITIONS
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The invention relates to a pharmaceutical composition comprising a plurality of controlled-release coated microparticles each comprising a floating core, on the surface of which is deposited a layer containing at least one active principle, said layer being covered with a controlled-release coating, characterized by the fact that said floating core is composed of cellulose acetate phthalate and has an apparent density of less than or equal to 0.6 g/mL and said coated microparticles have a density of less than or equal to 0.7 g/mL.
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- Amorphous 1-(9H-carbazol-4-yloxy)-3-[[2-(2-methoxyphenoxy)ethyl]amino]-2-propanol phosphate salt
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The present invention relates to a novel amorphous form of 1-(9H-carbazol-4-yloxy)-3-[[2-(2-methoxyphenoxy)ethyl]amino]-2-propanol phosphate (Carvedilol dihydrogen phosphate) of Formula (I), and a process for the preparation thereof.
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Page/Page column 3
(2010/04/23)
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- Novel amorphous carvedilol dihydrogen phosphate
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The present invention refers to an amorphous of carvedilol dihydrogen phosphate, the processes to obtain it, compositions containing this compound and its use to treat hypertension, congestive heart failure and angina.
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Page/Page column 5
(2009/01/24)
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- CARVEDILOL DIHYDROGEN PHOSPHATE MONOHYDRATE
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Disclosed herein is crystalline carvedilol dihydrogen phosphate monohydrate having high aqueous solubility and the process for preparation thereof. The invention further discloses methods for treating hypertension, congestive heart failure and angina in a
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Page/Page column 4
(2009/12/05)
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- STABLE AMORPHOUS FORM OF CARVEDILOL DIHYDROGEN PHOSPHATE WITH STABILIZER
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The present invention provides a novel stable amorphous form of carvedilol dihydrogen phosphate and the process for its preparation that involves reaction of carvedilol base with ortho phosphoric acid in the presence of stabilizer in a suitable solvent or
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Page/Page column 9-11
(2009/04/25)
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- NOVEL CRYSTALLINE FORM OF CARVEDILOL DIHYDROGEN PHOSPHATE AND RELATED PROCESSES
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The present patent application relates to a novel crystalline form (Form S) of Carvedilol dihydrogen phosphate and a process for its preparation. It also relates to an improved process for the preparation of Carvedilol dihydrogen phosphate.
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Page/Page column 10
(2009/10/30)
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- NOVEL CRYSTALLINE FORM B OF CARVEDILOL DIHYDROGEN PHOSPHATE
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A novel crystalline form B of carvedilol dihydrogen phosphate having X-ray diffraction pattern as shown in figure 1. A process for the preparation of crystalline form B of carvedilol dihydrogen phosphate according to claim 1 that comprises dissolving carv
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Page/Page column 7
(2009/03/07)
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- CARVEDILOL PHOSPHATE
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The invention encompasses novel amorphous and crystalline forms of carvedilol phosphate, carvedilol hydrogen phosphate, and carvedilol dihydrogen phosphate as well as methods of making the novel amorphous and crystalline forms. Also disclosed are pharmace
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Page/Page column 62; 63
(2008/06/13)
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- AMORPHOUS CARVEDILOL DIHYDROGEN PHOSPHATE
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The present invention provides amorphous form of carvedilol dihydrogen phosphate and processes for the preparation of it.
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Page/Page column 5-6
(2008/12/07)
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- CARVEDILOL COMPOSITIONS
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Amorphous carvedilol or its pharmaceutically acceptable salts, their processes of preparation and pharmaceutical compositions. An aspect of the invention relates to amorphous carvedilol phosphate, processes of preparation, and its pharmaceutical compositi
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Page/Page column 30-31
(2008/12/07)
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- Novel amorphous form of carvedilol phosphate and processes for the preparation thereof
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A novel form of amorphous carvedilol phosphate which is particularly suitable for pharmaceutical applications, and processes for preparing said novel form.
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Page/Page column 2
(2008/12/04)
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- NOVEL ANHYDROUS CRYSTALLINE FORM OF CARVEDILOL DIHYDROGEN PHOSPHATE
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The present invention provides a novel anhydrous crystalline form of carvedilol dihydrogen phosphate referred to as Form A having water content below 1.3%. Further it provides a process for the preparation of Form A. The PXRD, FT-IR and TGA data has been
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Page/Page column 4-5
(2008/12/07)
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- CARVEDILOL FREE BASE, SALTS, ANHYDROUS FORMS OR SOLVATE THEREOF, CORRESPONDING PHARMACEUTICAL COMPOSITIONS, CONTROLLED RELEASE FORMULATIONS, AND TREATMENT OR DELIVERY METHODS
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The present invention also relates to carvedilol free base, carvedilol salts, anhydrous forms, or solvates thereof, corresponding pharmaceutical compositions or controlled release formulations, and delivery or dosing methods of carvedilol forms to the low
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Page/Page column 98
(2008/06/13)
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- CARVEDILOL SALTS, CORRESPONDING COMPOSITIONS, METHODS OF DELIVERY AND/OR TREATMENT
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The present invention relates to a salt of carvedilol and/or corresponding solvates thereof, compositions containing such carvedilol and/or corresponding solvates thereof, and/or methods of using the aforementioned compound(s) in the treatment of certain
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Page/Page column 30
(2008/06/13)
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