Stability study of tetracyclines with respect to their use in slow release systems

In the aim of optimizing implantable slow-release systems for the local delivery of antibiotics, the stability of tetracyclines was studied in water at 37 degrees C or under gamma irradiation. Four tetracyclines in their chlorhydrate form were chosen depending on their hydrophilic/hydrophobic balance. Their chemical stability was established by HPLC, and biological stability by bacteriological tests. It was shown that methacycline and doxycycline are stable in water for three days. Tetracycline and minocycline exhibit limited decomposition (less than 10%) under the same conditions. So, in vitro drug release for at most three days, appears to be possible. Besides, all four tetracyclines either in powdered form or included in a calcium phosphate matrix, kept their bacteriological activity after gamma irradiation at 32.4 kGr. Consequently, the in vivo study of these implantable slow drug release systems, can be carried out.