15307-86-5Relevant articles and documents
Isolation and structural characterization of degradation products of aceclofenac by HPLC, HRMS and 2D NMR
Guduru, Santhosh,Anji Karun Mutha,Vijayabhaskar,Kaliyaperumal, Muralidharan,Korupolu, Raghu Babu,Bonige, Kishore Babu,Rumalla, Chidananda Swamy
, p. 851 - 854 (2019)
The stability of aceclofenac under stress conditions was assessed to identify the degradation products. So, it was subjected to stress conditions like acid, base and oxidation, according to ICH guideline Q1A (R2). One degradation product formed when the drug was subjected to acid stress. Three degradation products were formed during the basic stress condition. The drug substance was found to be stable to oxidative stress. The degradants formed during the stress were separated on a C-18 column using gradient preparative HPLC elution. The only product (DP-2) formed during the acid stress and this one is same as of one of the three degradation products (DP-1, DP-2, DP-3) were formed during base stress. 1D and 2D NMR spectra and mass spectral analysis supported the proposed structures for the products. The products DP-2 and DP-3 have been reported earlier but this is the first report of product DP-1 as a degradation product of aceclofenac.
Morpholinoalkyl ester prodrugs of diclofenac: Synthesis, in vitro and in vivo evaluation
Tammara,Narurkar,Crider,Khan
, p. 644 - 648 (1994)
Morpholinoalkyl esters (HCl salts) of diclofenac (1) were synthesized and evaluated in vitro and in vivo for their potential use as prodrugs for oral delivery. Prodrugs were freely soluble in simulated gastric fluid (SGF) and pH 7.4 phosphate buffer and showed a minimum of a 2000-fold increase in solubility over the parent drug. All prodrugs were more lipophilic than 1 as indicated by n-octanol/pH 7.4 buffer partition coefficients, but less lipophilic than 1 in terms of n-octanol/SGF partition coefficients. Potentiometrically determined ionization constants (pK(a)s) were in the range of 7.52 to 8.40 at 25 °C. The chemical and enzymatic hydrolyses of prodrugs were evaluated in SGF/pH 7.4 phosphate buffer and rat plasma, respectively, at 37 °C. All prodrugs were quantitatively hydrolyzed to 1 by either chemical and/or enzymatic means. An increase in carbon chain length rendered the prodrugs more stable at pH 7.4, but less stable in SGF. In general, the esters were hydrolyzed rapidly in rat plasma at 37 °C, the half-lives of hydrolysis being in the range of 4.85 to 23.49 min. Based on in vitro results, prodrug 2 was chosen to evaluate solid-state stability, bioavailability, and in vivo ulcerogenicity. At elevated temperatures, the solid-state decomposition of 2 followed biphasic kinetics, with rapid decomposition occurring initially. The extent, but not the rate, of absorption was significantly greater in rats for prodrug 2 than 1 following single dose oral administration. Prodrug 2 was significantly less irritating to gastric mucosa than 1 following single and chronic oral administration in rats.
Synthesis and spectroscopic/DFT structural characterization of coordination compounds of Nb(V) and Ti(IV) with bioactive carboxylic acids
De Palo, Alice,Biancalana, Lorenzo,Bortoluzzi, Marco,Alessandra Martini, Maria,Marchetti, Fabio,Pampaloni, Guido
, p. 208 - 214 (2018)
The reactions are reported of NbX5 (X = Cl, Br), TiCl4 and Ti(OiPr)4 with a selection of carboxylic acids exhibiting a known biological role, in a chlorinated solvent. The reactions of NbX5 with acetylsalicylic acid (aspirin) proceeded with selective deacetylation of the organic reactant and formation of the salicylate complexes NbX4(C7H5O3) (1a, X = Cl; 1b, X = Br) in 60–65% yields. NbCl5 reacted with diclofenac and ethacrynic acid (EA-CO2H) to give NbCl3[κ3O,O,N-O2CCH2(C6H4)NC6H3Cl2], 2 (80% yield), and NbCl4(O2C-EA), 3 (72% yield), respectively. Ti(OiPr)4 reacted with ethacrynic acid giving Ti(OiPr)2(O2C-EA)2, 4, in 74% yield, as a mixture of two isomers. All the products were characterized by means of analytical and spectroscopic methods, moreover DFT studies were carried out to give insight into structural features.
Stability indicating methods for the determination of aceclofenac
Hasan,Abdel-Elkawy,Elzeany,Wagieh
, p. 91 - 99 (2003)
Five new selective, precise and accurate methods for the determination of aceclofenac in the presence of its degradation product; diclofenac are described. Method A utilizes third derivative spectrophotometry at 242 nm. Method B is RSD1 spectrophotometric method based on the simultaneous use of the first derivative of ratio spectra and measurement at 245 nm. Method C is a pH-induced difference (ΔA) spectrophotometry using UV measurement at 273 nm. Method D is a spectrodensitometric one, which depends on the quantitative densitometric evaluation of thin layer chromatogram of aceclofenac at 275 nm. Method E is RP-HPLC that depends on using methanol: water (60:40 v/v) as mobile phase at a flow rate of 1 ml/min and UV detection at 275 nm. Regression analysis of a beer's plot showed good correlation in the concentration ranges 5-40, 10-40, 15-50, 50-200, 1-50 μg/ml for methods A, B, C, D and E, respectively. These methods are suitable as stability indicating methods for the determination of aceclofenac in presence of its main degradation product, diclofenac. The proposed methods were applied for the analysis of the drug in its pharmaceutical formulation and the results obtained were compared with those obtained with the official B.P. method.
Pd(OH)2/C, a Practical and Efficient Catalyst for the Carboxylation of Benzylic Bromides with Carbon Monoxide
Wakuluk-Machado, Anne-Marie,Dewez, Damien F.,Baguia, Hajar,Imbratta, Miguel,Echeverria, Pierre-Georges,Evano, Gwilherm
, p. 713 - 723 (2020/02/04)
A simple, efficient, cheap, and broadly applicable system for the carboxylation of benzylic bromides with carbon monoxide and water is reported. Upon simple reaction with only 2.5 wt % of Pearlman's catalyst and 10 mol % of tetrabutylammonium bromide in tetrahydrofuran at 110 °C for 4 h, a range of benzylic bromides can be smoothly converted to the corresponding arylacetic acids in good to excellent yields after simple extraction and acid-base wash. The reaction was found to be broadly applicable, scalable, and could be successfully extended to the use of ex situ-generated carbon monoxide and applied to the synthesis of the nonsteroidal anti-inflammatory drug diclofenac.
A diclofenac - glycine - [...], preparation method and application
-
Paragraph 0029; 0030, (2019/06/30)
The invention discloses a diclofenac - glycine - [...], preparation method and application. The conjugate is to glycine as the connecting arm, respectively with the diclofenac and [...]; diclofenac is connected with glycine through amide linkage; diclofenac - glycine conjugate with resveratrol through connected [...] site. Because of the introduction of the glycine, to increase the solubility of the conjugate, diclofenac and resveratrol introduced into the coupling anti- arthritis significantly enhanced, the bad reaction is reduced, the safety is higher; the conjugate synthesis method is simple, and is suitable for industrial production.
