A comparison of the stability of ertapenem and meropenem in pharmaceutical preparations in solid state

The following first-order rate constants of the degradation of ertapenem in INVANZ and meropenem in MERONEM were determined: (a) in dry air at 363, 373, 378, 383, 388, 393 K; (b) at increased relative air humidity (76.4% RH) at 313, 323, 333 and 343 K; (c) at increased relative air humidity (50.9, 60.5, 66.5, 76.4% RH—ertapenem and 50.9, 66.5, 76.4 and 90.0% RH—meropenem) at 333 K. The dependence ln ki = f(RH%) was described by the equations: ln ki = (6.63 ± 1.22) × 10−2 × (RH%) − 13.36 ± 1.68 (ertapenem) and ln ki = (4.22 ± 2.98) × 10−2 × (RH%) − 12.14 ± 2.16 (meropenem). The dependence ln ki = f(1/T) was described by equations: ln ki = 19.4 ± 2.6 − (9230 ± 800)(1/T) for ertapenem, at 76.4% RH; ln ki = 11.5 ± 4.9 − (9880 ± 1800)(1/T) for ertapenem in dry air; ln ki = 14.8 ± 11.9 − (7785 ± 3905)(1/T) for meropenem, at 76.4% RH; ln ki = 37.6 ± 7.73 − (18385 ± 2930)(1/T) for meropenem in dry air. The thermodynamic parameters Ea, ΔH≠ and ΔS≠ of the degradation of ertapenem and meropenem were calculated. The difference between the influence of temperature on the stability of ertapenem and meropenem was not significant at 76.4% RH. In dry air (363–393 K) this influence was greater in the case of meropenem. The degradation of ertapenem was slower in this temperature range. Humidity was a significant factor affecting the degradation of these antibiotics and it influenced their stability is similar ways.