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 k(i) = f(RH%) was described by the equations: ln k(i) = (6.63+/-1.22) x 10(-2) x (RH%)-13.36 +/- 1.68 (ertapenem) and ln k(i) = (4.22 +/- 2.98) x 10(-2) x (RH%)-12.14 +/- 2.16 (meropenem). The dependence lnk(i)=f(1/T) was described by equations: ln k(i) =19.4 +/- 2.6-(9230 +/- 800)(1/T) for ertapenem, at 76.4% RH; ln k(i) = 11.5 +/- 4.9-(9880 +/- 1800)(1/T) for ertapenem in dry air; ln k(i) = 14.8 +/- 11.9-(7785 +/- 3905)(1/T) for meropenem, at 76.4% RH; ln k(i) = 37.6 +/- 7.73-(18385 +/- 2930)(1/T) for meropenem in dry air. The thermodynamic parameters E(a), DeltaH( not equal) and DeltaS( not equal) 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.
Cielecka-Piontek
Judyta
J
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Poznań University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, Poland.
Zajac
Marianna
M
Jelińska
Anna
A
D000465:Algorithms; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004349:Drug Packaging / Q000379:methods; D004355:Drug Stability; D004356:Drug Storage / Q000379:methods; D004400:Dyphylline / Q000032:analysis / Q000737:chemistry; D019277:Entropy; D000077727:Ertapenem; D006813:Humidity; D000077731:Meropenem; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000737:chemistry* / Q000592:standards; D012015:Reference Standards; D053719:Tandem Mass Spectrometry / Q000379:methods; D013696:Temperature; D013845:Thienamycins / Q000032:analysis / Q000737:chemistry*; D013997:Time Factors; D054928:Validation Studies as Topic; D047090:beta-Lactams / Q000032:analysis / Q000737:chemistry*
D004364:Pharmaceutical Preparations; D013845:Thienamycins; D047090:beta-Lactams; D004400:Dyphylline; D000077731:Meropenem; D000077727:Ertapenem