Marianna Zając

Evaluation of stability of cefuroxime axetil in solid state.

The effect of temperature and relative atmospheric humidity on the stability of the crystalline form of cefuroxime axetil (CFA) in solid state was investigated. CFA is a mixture of diastereomers A and B. Changes in the concentration of the two diastereomers (A and B) of CFA were recorded by means of HPLC with UV detection. The degradation of diastereomers of CFA occurring at 0% relative humidity (RH) of the ambient air is a reversible first order reaction, while that occurring in humid air (RH>50%) is an autocatalytic first order reaction relative to substrate concentration. Although it has been found, that diastereomer B is the more stable isomer, humidity has a stronger effect on this very diastereomer.

A comparison of the stability of doxorubicin and daunorubicin in solid state

The degradation of doxorubicin and daunorubcin in the solid state was studied using an HPLC method with UV detection (LiChrospher RP-18, 5 microm, 250 mm x 4 mm; mobile phase: acetonitrile-solution A 1:1, v/v (solution A: 2.88 g of laurisulfate sodium and 1.6 ml of phosphoric acid(V) in 1000 ml); flow rate - 1.4 ml min(-1); UV detection - 254 nm). The degradation of doxorubicin was a first-order reaction depending on the substrate concentration and daunorubicin degraded according to the kinetic model of autocatalysis. The dependence lnk(i)=f(1/T) was described by the equations lnk(DOX)=40.0+/-15.6-(19804+/-5682) (1/T) and lnk(DAU)=35.9+/-11.3-(16581+/-3972) (1/T) at 76.4% RH. The dependence lnk(i)=f(RH%) was described by the equations lnk(DOX)=(8.80+/-3.60) x10(-2) (RH%)-(21.50+/-2.57) and lnk(DAU)=(6.63+/-1.22)x10(-2) (RH%)-(13.35+/-1.68). The thermodynamic parameters (E(a,) DeltaH(not = a), DeltaS(not = a)) of the degradation of doxorubicin and daunorubicin were calculated. Although the degradation of doxorubicin was slower at increased temperature (353-373 K) and relative air humidity (50.9-90.0%), the differences between the influence of temperature and relative air humidity on the stability doxorubicin and of daunorubicin were not significant.

Kinetics of cefamandole nafate degradation in solid phase

The influence of temperature and relative humidity (RH) on the stability of cefamandole (CM) nafate sodium in the solid phase was investigated. Changes in the concentration of cefemandole nafate sodium were recorded using HPLC with UV detection. The method was validated for the following parameters: selectivity, linearity, precision, limit of detection and sensitivity. It showed good linearity (r=0.9996) in the range 0.4 x 10(-4)-5.6 x 10(-4) g ml(-1) using a LiChrospher RP-18 column and as mobile phase acetonitryle-triethylamine (10% v/v, adjusted to pH 2.5 with phosphoric acid (84%) and diluted with water) (35:65). The degradation of CM occurring at 0% RH of the ambient air and at air humidity RH>50% is a first-order reaction relative to substrate concentration. The first-order rate constants (k) were determined for CM degradation in dry air at 373, 383, 388 and 393 K, at air humidity RH=76.4% at 323, 333, 343 and 353 K, and at 353 K at air humidity RH>50%. The kinetic and thermodynamic parameters of the decomposition were calculated.