Available online at www.sciencedirect.com Journal of Pharmaceutical and Biomedical Analysis 46 (2008) 52–57 A comparison of the stability of ertapenem and meropenem in pharmaceutical preparations in solid state Judyta Cielecka-Piontek, Marianna Zaj˛ ac ∗ , Anna Jeli ´ nska Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Pozna´ n University of Medical Sciences, Grunwaldzka 6, 60-780 Pozna´ n, Poland Received 18 April 2007; received in revised form 19 July 2007; accepted 28 August 2007 Available online 1 September 2007 Abstract 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) × 10 -2 × (RH%) - 13.36 ± 1.68 (ertapenem) and ln k i = (4.22 ± 2.98) × 10 -2 × (RH%) - 12.14 ± 2.16 (meropenem). The dependence ln k 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 , H = and S = 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. © 2007 Elsevier B.V. All rights reserved. Keywords: HPLC; Validation; Ertapenem; Meropenem; Stability in solid state; Kinetic and thermodynamic parameters 1. Introduction Ertapenem and meropenem are parenteral carbapenems containing a 1--methyl group, which renders these antibiotics stable to renal dehydropeptidase (DHP-I) [1]. Ertapenem and meropenem have a very broad spectrum of antibacterial activity against the majority of Gram-positive and Gram-negative bacteria [2]. Compared to ertapenem, meropenem is more active against Enterobacteriaceae and Pseu- ∗ Corresponding author. Tel.: +48 61 8546650; fax: +48 61 8546652. E-mail address: mzajac@amp.edu.pl (M. Zaj˛ ac). domonas aeruginosa [1]. The introduction of meta-substituted benzoic acid as a substituent into the structure of ertapenem increases the plasma half-life of ertapenem because of its greater affinity for plasma proteins [3]. Similarly to other -lactam antibiotics, the carbapenems are easily degraded in aqueous solutions and in solid state. The hydrolysis of the -lactam ring occurs in dilute aque- ous solutions of ertapenem (<1 mg ml -1 ) [4]. General and specific acid–base hydrolysis of ertapenem at pH 0.42–12.5, at 303, 313, 323 and 333 K was studied. Specific acid–base catalysis involves: (a) hydrolysis of ertapenem catalysed by 0731-7085/$ – see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.jpba.2007.08.024