Concentrated solutions of doxycycline are often added to drinking water of animals for oral antibiotic therapy. However, stability concerns of doxycycline in solution involve an accurate selection of the solvent system to ensure that the active substance will remain within the acceptance range during the product shelf-life and to avoid sub-therapeutic dosage. Different solvent systems have been evaluated in order to determine their influence on the stability of concentrated doxycycline solutions. The results showed differences in the degradation kinetics of doxycycline depending on the co-solvent used and they permitted to select a solvent system for liquid doxycycline hyclate formulations with low rate of degradation even after several months of storage. So, the inclusion of ethanol together with propylene glycol as main excipient was found to be beneficial, while no benefit was observed concerning the addition of citric acid. Once administered to drinking water, the solutions were stable for 24 h with no influence of the solvent system.
The inclusion of ethanol as excipient in the solvent system improved considerably the stability of DOX formulations over a longer period. It reduces the formation of degradation products and in particular the epimerisation in C4. The use of citric acid has no noticeable effect on the stability of the concentrated solution and it is also not necessary for stabilisation once the formulation is dosed in drinking water of animals. Once administered to drinking water, most solutions are stable during 24 h, independent of the solvent systems examined, which all contained propylene glycol as main solvent.