Degradation patterns of tetracycline antibiotics in reverse micelles and water

Abstract

The objective of this study was to determine the chemical stability of tetracycline and oxytetracycline hydro-chlorides in reverse micelles. Their reverse micellar solutions were prepared using cetyltrimethylammonium bromide, water and ethyl formate. The aqueous solutions of the tetracycline antibiotics were also prepared for comparison. The reverse micellar and aqueous solutions were stored at 37 degrees C. Samples were analyzed by high performance liquid chromatography. When evaluation was performed on an aqueous tetracycline HCl solution, its half-life was estimated to be 329 h. Its chemical stability was not improved after being dissolved in the reverse micelles, and a similar half-life of 330 h was observed. However, there were noticeable differences between the two systems in terms of degradation kinetics and degradation byproducts. On the other hand, oxytetracycline HCl was unstable in water so that its half-life was only 34 h. Very interestingly, pronounced improvement in stability was attained with the reverse micellar system: upon dissolving in the reverse micelles, its half-life was increased to 2402 h. There were also marked differences in degradation patterns and mechanisms of oxytetracycline HCl in water and the reverse micelles. Our study indicates that the reverse micellar system has potential applications in solubilizing and stabilizing oxytetracycline HCl, thereby contributing to the development of its dosage forms.

Gastroretentive montmorillonite-tetracycline nanoclay for the treatment of Helicobacter pylori infection

“…With regard to TC biological activity, its adsorption onto MM without compromising the bactericidal activity was demonstrated (Parolo et al, 2010). Moreover, considering TC degradation in aqueous solutions (Kang et al, 2012;Loftin et al, 2008;Pena et al, 1998) although the high half-life estimated by other Authors in more than 300h (Sah, 2006), a greater chemical stabilization might be provided by the adsorption process onto MM (Chang et al, 2009;Sah, 2006).…”

Evaluating approved and alternative treatments against an oxytetracycline-resistant bacterium responsible for European foulbrood disease in honey bees

“…Larval treatment with 100 μg/mL OTC, corresponding to ~ 3× the MIC in vitro, was necessary to reduce larval mortality to the same level as the uninfected GC group. After six days of in vitro rearing, larvae treated with 100 μg/mL OTC were calculated to receive a total dose of 105–120 μg/g OTC per larvae, not accounting for the 34-h half-life of OTC in water 28 . Accordingly, the dose of OTC per larva in vitro is ~ 10× the quantity of OTC previously reported in honey bee larvae from a field colony treated with 300 mg OTC 39 .…”

“…Antibiotics were included in diets daily for either 4 or 5 days depending on the experimental design, Thus, total 4 or 5-day doses were of 0.14–140 μg or 0.16–160 μg OTC and 4.62–462 μg or 5.28–528 μg of TYL and LMC not accounting for the half-lives of OTC, TYL, and LMC, which in water are 34 h, 200 d, and 30 h, respectively 28 – 30 .…”

Effects of Incubation Time and Inoculation Level on the Stabilities of Bacteriostatic and Bactericidal Antibiotics against Salmonella Typhimurium

“…The significant losses in tetracycline and cephalothin activities were observed at ½ MIC and 1 MIC, respectively, against ASST ( Figure 1 c,d). These antibiotics were unstable in aqueous solution, leading to a reduced half-life [ 15 , 16 ]. As shown in Figure 2 , tetracycline, ciprofloxacin, and tobramycin were unstable to media at ½ MIC against ARST.…”