Kinetic studies of the degradation of an aminopenicillin antibiotic (amoxicillin trihydrate) in aqueous solution using heat conduction microcalorimetry

Abstract

Recent developments in isothermal microcalorimetry allow the direct determination of kinetic and thermodynamic parameters for slow reactions from studies conducted at appropriate temperatures and under designated environmental control. The degradation kinetics of amoxicillin trihydrate has been investigated as a function of pH (1-10) and temperature (303.15-318.15 K) at 0.5 M ionic strength using heat conduction microcalorimetry. Equations were developed incorporating calorimetric accessible data, rate constants and change in enthalpy, which showed that the degradation of amoxicillin trihydrate in aqueous solution followed pseudo-first-order kinetics under our experimental conditions. The enthalpy of degradation reaction was found to be exothermic in nature. The values of the rate constant k for individual steps were determined from the values of the overall rate constants at different pH. Energy of activation of overall reaction as a function of pH and for individual rate constants was determined. The log k-pH profiles indicated specific-acid and specific-base catalysis and there were inflection points near pH 3 and pH 7 corresponding to the pKa1 and pKa2 values. Quantitatively, there was good correlation between calorimetric determined half-life (t1/2) and the literature value in the acidic region determined by other methods at 310.15 K. The presence of a beta-lactam ring and of an alpha-amino group in the C-6 side chain played a critical role in the degradation of amoxicillin trihydrate and the zwitterionic form of the drug was found to be more stable.

Development and validation of RP-HPLC method for determination of amoxicillin residues and application to NICOMAC coating machine

“…2 AMO is official in British Pharmacopeia (BP), 1 European Pharmacopeia (EP) 3 and United States Pharmacopeia (USP) 4 , they include HPLC method for its determination. It is still a limited number of analytical methods that are reported for the determination of AMO including kinetics degradation, [5][6][7] spectrophotometric, [8][9][10][11][12][13] UHPLC UPLC and mass spectrometry, [14][15][16][17][18][19] thin layer chromatography (TLC), [20][21][22] capillary electrophoresis, [23][24][25][26] high performance liquid chromatography (HPLC), [27][28][29][30][31] in vitro dissolution studies, [32][33][34][35][36] amoxicillin residues in animal tissues using SPE-LC, 37 SPE-cation exchange, 38 in eggs using HPLC-FLD, 39 or HPLC-MS 40 and in commercial meat and milk samples 41 using HPLC-FLD. According to the best of our knowledge there is no validated method for the determination of amoxicillin residues and application to cleaning machine in pharmaceutical industries.…”

Drug Development for Eradication with InclusionComplex of Multifunctional-modifiedβCD

“…there was clearly strong inhibition of hydrolysis, with a reduced [10]. We also found that the single substituent group on the prima- A further purpose for the multifunctional complex was to induce affinity between the linker and bacteria; this was tested by quantum chemical methods.…”

Mucoadhesive and muco-penetrating delivery systems for eradication of helicobacter pylori

“…[62][63][64] In 2005, Liu et al [65] prepared a amoxicillin-loaded mucoadhesive microsphere of ethyl cellulose and carbomer 937 by the solvent evaporation method and observed low acidic degradation of amoxicillin in the prepared microspheres. Also, mucoadhesive microspheres of amoxicillin could stay in the gastrointestinal tract for a longer period of time and resulted in higher H. pylori clearance.…”