The Radiostability of Meropenem Trihydrate in Solid State

Abstract

The influence of ionising radiation on the physicochemical properties of meropenem trihydrate in solid state was studied for doses of e-beam radiation: 25 kGy and 400 kGy. In the first part of our studies, we evaluated the possibility of applying radiosterilization to obtain sterile meropenem. No changes for meropenem irradiated with a dose of 25 kGy, the dose required to attain sterility, was confirmed in the results of spectroscopic (FT-IR), thermal (DSC, TGA) and X-ray powder diffraction (XRPD) studies. The radiation dose of 25 kGy produces no more than about 1500 ppm of radical defects. The chromatographic studies of irradiated meropenem in solutions did not show any chemical degradation. Moreover, the antimicrobial activity of meropenem irradiated with the dose of 25 kGy was unchanged. Based on the received results, we can conclude that radiostelization is a promising, alternative method for obtaining sterile meropenem. In the second part of the research, meropenem was exposed to e-beam radiation at the 400 kGy dose rate. It was confirmed, that reducing of antimicrobial activity could be connected with the degradation of β-lactam ring and changes in the trans-hydroxyethyl group. Apart from chemical changes, changes in the physical stability of irradiated meropenem (400 kGy) was also observed.

The Radiation Sterilization of Imipenem and Cilastatin in the Solid State

“…The literature data confirms that the most common problem encountered after radiosterilisation of solid drugs is discoloration or yellowing (17)(18). In our study also a colour change of samples after exposure to radiation was reported ñ from white to slight beige.…”

“…Previous research concerning the radiostability of β-lactams antibiotics has confirmed their susceptibility to degradation (12)(13)(14)(15)(16)(17).…”

The Radiation Sterilization of Ertapenem Sodium in the Solid State

“…Previous research concerning the radiostability of β-lactams antibiotics have confirmed their susceptibility to degradation [7,8,9,10,11,12,13]. Test results—both identification methods and stability tests—carried out for solid ERP reflect this statement.…”

“…The literature data confirm that discoloration or yellowing is the most common problem that is encountered after radiosterilisation of solid drugs [11]. What is particularly important, after dissolving the ERP irradiated samples in water for injections, we get clear and colorless solutions.…”

“…For this reason, it is particularly important to choose the suitable sterilization method for ERP and irradiation seems to be the most advantageous approach. However, the use of this method requires detailed studies and confirmation of the impact of irradiation on the pharmaceutical properties and structure of the drug [7,8,9,10,11,12,13].…”