| 1. |
- Al-Hayali, Amani Ibraheem Younis, et al.
(författare)
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Dissolution and precipitation behavior of ternary solid dispersions of ezetimibe in biorelevant media
- 2017
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Ingår i: Drug Development and Industrial Pharmacy. - : Informa UK Limited. - 0363-9045 .- 1520-5762. ; 43:1, s. 79-88
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Tidskriftsartikel (refereegranskat)abstract
- The effects of different formulations and processes on inducing and maintaining the supersaturation of ternary solid dispersions of ezetimibe (EZ) in two biorelevant media fasted-state simulated intestinal fluid (FaSSIF) and fasted-state simulated gastric fluid (FaSSGF) at different temperatures (25 °C and 37 °C) were investigated in this work.Ternary solid dispersions of EZ were prepared by adding polymer PVP-K30 and surfactant poloxamer 188 using melt-quenching and spray-drying methods. The resulting solid dispersions were characterized using scanning electron microscopy, differential scanning calorimetry (DSC), modulated DSC, powder X-ray diffraction and Fourier transformation infrared spectroscopy. The dissolution of all the ternary solid dispersions was tested in vitro under non-sink conditions.All the prepared solid dispersions were amorphous in nature. In FaSSIF at 25 °C, the melt-quenched (MQ) solid dispersions of EZ were more soluble than the spray-dried (SD) solid dispersions and supersaturation was maintained. However, at 37 °C, rapid and variable precipitation behavior was observed for all the MQ and SD formulations. In FaSSGF, the melting method resulted in better solubility than the spray-drying method at both temperatures.Ternary solid dispersions show potential for improving solubility and supersaturation. However, powder dissolution experiments of these solid dispersions of EZ at 25 °C may not predict the supersaturation behavior at physiologically relevant temperatures.
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| 2. |
- Alhalaweh, Amjad, et al.
(författare)
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1:1 and 2:1 urea-succinic acid cocrystals : structural diversity, solution chemistry, and thermodynamic stability
- 2010
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Ingår i: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 10:11, s. 4847-4855
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this work was to study the crystal structures of 1:1 and 2:1 urea-succinic acid (U-SA) cocrystals and to investigate the role of solution chemistry in the formation and stability of different stoichiometric cocrystals. The structural diversity of other urea-dicarboxylic acid cocrystals is also discussed. The 1:1 U-SA cocrystal was stabilized by an acid-amide heterosynthon while acid-amide heterosynthons and amide-amide homosynthons stabilized the 2:1 cocrystals. The hydrogen bonding motifs in 1:1 and 2:1 U-SA cocrystals were consistent with other urea-dicarboxylic acid systems with similar stoichiometries. The 1:1 cocrystals were transformed to 2:1 cocrystals upon slurrying in various solvents at 25 °C. The phase solubility diagram was used to define the stability regions of different solid phases in 2-propanol at 25 °C. While no phase stability region for 1:1 cocrystal could be found, the stable regions for the 2:1 cocrystals and their pure components were defined by eutectic points. The solubility of the 2:1 cocrystals was dependent on the concentration of the ligand in the solution and explained by the solubility product and 1:1 solution complexation. The mathematical models predicting the solubility of the 2:1 cocrystals were evaluated and found to fit the experimental data
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| 3. |
- Basavoju, Srinivas, et al.
(författare)
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Indomethacin-saccharin cocrystal : design, synthesis and preliminary pharmaceutical characterization
- 2008
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Ingår i: Pharmaceutical research. - : Springer. - 0724-8741 .- 1573-904X. ; 25:3, s. 530-541
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. To design and prepare cocrystals of indomethacin using crystal engineering approaches, with the ultimate objective of improving the physical properties of indomethacin, especially solubility and dissolution rate. Materials and Methods. Various cocrystal formers, including saccharin, were used in endeavours to obtain indomethacin cocrystals by slow evaporation from a series of solvents. The melting point of crystalline phases was determined. The potential cocrystalline phase was characterized by DSC, IR, Raman and PXRD techniques. The indomethacin-saccharin cocrystal (hereafter IND-SAC cocrystal) structure was determined from single crystal X-ray diffraction data. Pharmaceutically relevant properties such as the dissolution rate and dynamic vapour sorption (DVS) of the IND-SAC cocrystal were evaluated. Solid state and liquid-assisted (solvent-drop) cogrinding methods were also applied to indomethacin and saccharin. Results. The IND-SAC cocrystals were obtained from ethyl acetate. Physical characterization showed that the IND-SAC cocrystal is unique vis-a-vis thermal, spectroscopic and X-ray diffraction properties. The cocrystals were obtained in a 1:1 ratio with a carboxylic acid and imide dimer synthons. The dissolution rate of IND-SAC cocrystal system was considerably faster than that of the stable indomethacin gamma-form. DVS studies indicated that the cocrystals gained less than 0.05% in weight at 98%RH. IND-SAC cocrystal was also obtained by solid state and liquid-assisted cogrinding methods. Conclusions. The IND-SAC cocrystal was formed with a unique and interesting carboxylic acid and imide dimer synthons interconnected by weak N-H center dot center dot center dot O hydrogen bonds. The cocrystals were non-hygroscopic and were associated with a significantly faster dissolution rate than indomethacin (gamma-form).
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| 4. |
- Basavoju, Srinivas, et al.
(författare)
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Pharmaceutical cocrystal and salts of norfloxacin
- 2006
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Ingår i: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 6:12, s. 2699-2708
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the structural and pharmaceutical properties of norfloxacin (a poorly soluble antibacterial drug), its cocrystal, and salts. Norfloxacin in the anhydrous form (form A, 1) was crystallized. It was cocrystallized with isonicotinamide (2), and organic salts were prepared with succinic acid, malonic acid, and maleic acid (3-5, respectively). These phases were characterized by differential scanning calorimetry (DSC), infrared (IR) and Raman spectroscopy, and powder X-ray diffraction (PXRD). Single-crystal X-ray diffraction data were obtained, and crystal structures were solved. The apparent solubility of these phases was determined. Robust O-H⋯O, O-H⋯O-, O-H⋯N, N-H⋯O, N+-H-O -, and N-H⋯N interactions were present in all these structures. Quinolone moieties in these structures stack with π⋯π interactions and form channels to include CHCl3 or H2O. Herein we report a new cocrystal and salts of norfloxacin with improved aqueous solubility
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| 5. |
- Basavoju, Srinivas, et al.
(författare)
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Pharmaceutical salts of fluoroquinolone antibacterial drugs with acesulfame sweetener
- 2012
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Ingår i: Molecular Crystals and Liquid Crystals. - : Informa UK Limited. - 1542-1406 .- 1563-5287. ; 562:1, s. 254-264
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Tidskriftsartikel (refereegranskat)abstract
- Novel organic salts of norfloxacin and ciprofloxacin with artificial sweeteners such as saccharin and acesulfame were prepared. The two salts 1 and 2 were characterized by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). Finally, the crystal structures were solved by single crystal X-ray diffraction data and the structures were analyzed in terms of supramolecular synthons. In norfloxacin acesulfamate 1, two norfloxacin cations and two acesulfame anions form an eight membered cyclic tetramer supramolecular synthon. The salt, ciprofloxacin acesulfamate 2, has a similar structure as salt 1. This study contributes the importance of crystal engineering and supramolecular chemistry to the pharmaceutical applications in terms of interactions and structural correlations in the design of new solid phases. Supplemental materials are available for this article. Go to the publisher's online edition of Molecular Crystals and Liquid Crystals to view the free supplemental file.
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| 6. |
- Lou, Benyong, et al.
(författare)
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1-Ethyl-6-fluoro-7-(4-formylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
- 2007
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Ingår i: Acta Crystallographica Section E. - : International Union of Crystallography. - 1600-5368. ; 63:11, s. o4281-
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Tidskriftsartikel (refereegranskat)abstract
- The formylation reaction of norfloxacin with N,N-dimethylformamide (DMF) gives the title compound, C17H18FN3O4. In the structure, molecules are connected via weak C-HO, C-H and - interactions [perpendicular distance 3.423 Å and centroid-centroid distance 3.8141 Å].
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| 7. |
- Lou, Benyong, et al.
(författare)
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Hydrogen-bonding interactions in the 4-aminobenzoic acid salt of atenolol monohydrate
- 2007
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Ingår i: Acta Crystallographica Section C. - : International Union of Crystallography. - 0108-2701 .- 1600-5759. ; 63:12, s. 714-716
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Tidskriftsartikel (refereegranskat)abstract
- Atenolol {or 4-[2-hydroxy-3-(isopropylamino)propoxy]phenyl-acetamide} crystallizes with 4-aminobenzoic acid to give the salt {3-[4-(aminocarbonylmethyl)phenoxy]-2-hydroxypropy1}- isopropylammonium 4-aminobenzoate monohydrate, C14H23- N2O3*C7H6NO2-*H2O. In the crystal structure, the water molecule, the carboxylate group of 4-aminobenzoate, and the hydroxy and ether O atoms of atenolol form a supramolecular R33(11) heterosynthon. Three other types of supramolecular synthons link the asymmetric unit into a two-dimensional structure.
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| 8. |
- Lou, Benyong, et al.
(författare)
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Monohydrous dihydrogen phosphate salts of norfloxacin and ciprofloxacin
- 2007
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Ingår i: Acta Crystallographica Section C. - 0108-2701 .- 1600-5759. ; 63:12, s. 731-733
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Tidskriftsartikel (refereegranskat)abstract
- Norfloxacin and ciprofloxacin crystallize with phosphoric acid in aqueous solution to give the salts 4-(3-carboxy-1-ethyl-6-fluoro-4-oxo-1,4-dihydro-7-quinolyl)piperazinium dihydrogenphosphate monohydrate, C16H19FN3O3(+) x H2PO4(-) x H2O, and 4-(3-carboxy-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-7-quinolyl)piperazinium dihydrogenphosphate monohydrate, C17H19FN3O3(+) x H2PO4(-) x H2O, respectively. In the crystal structures, the phosphate anions and the piperazine rings of norfloxacin or ciprofloxacin form a 12-membered supramolecular synthon, viz. R4(4)(12). The synthons R4(4)(12) and R2(2)(8) formed between adjacent phosphate anions result in the three-dimensional structures.
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| 9. |
- Lou, Benyong, et al.
(författare)
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Polymorph control of Felodipine form II in an attempted cocrystallization
- 2009
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Ingår i: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 9:3, s. 1254-1257
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Tidskriftsartikel (refereegranskat)abstract
- The metastable form II of racemic felodipine was obtained in an attempted cocrystallization with isonicotinamide. Its low temperature crystal structure was characterized by a 1D hydrogen-bonded chain consisting of four independent felodipine molecules.
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| 10. |
- Shimpi, Manishkumar, et al.
(författare)
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New cocrystals of ezetimibe with l-proline and imidazole
- 2014
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Ingår i: CrystEngComm. - : Royal Society of Chemistry (RSC). - 1466-8033 .- 1466-8033. ; 16:38, s. 8984-8993
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Tidskriftsartikel (refereegranskat)abstract
- The objectives of the study were to screen and prepare cocrystals of anti-cholesterol drug ezetimibe (EZT) with the aim of increasing its solubility and dissolution rate. Thermodynamic phase diagram based high throughput screening was performed using wet milling/grinding or solution crystallization methods. A large number of coformers were tested and the resulting solids were preliminarily characterized using X-ray powder diffraction (PXRD) and Raman spectroscopy. Potential cocrystals of EZT with l-proline and imidazole and a solvate formamide were identified in the screening experiments. The cocrystal hits were further characterized by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), solution Proton nuclear magnetic resonance spectroscopy (1H-NMR) and single crystal XRD. The dissolution properties and stability of cocrystals were determined. Single-crystal X-ray diffraction data were obtained for EZT, EZT-IMI cocrystal and formamide solvate of ezetimibe. All three systems were crystallized in non-centrosymmetric orthorhombic space group P212121with Z = 4. Robust O-H⋯O, O-H⋯N, N-H⋯O and C-H⋯O hydrogen bonds played an important role in all these crystal structures. EZT-PRO cocrystal showed improved apparent solubility and solid state stability
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