Investigation of the Effect of pH on the Adsorption-Desorption of Doxycycline in Feed for Small Ruminants.

Abstract

Orally administered tetracycline antibiotics interact with feed, which may impact their bioavailability and efficacy. Therefore, the pH-dependent adsorption of doxycycline and its interaction with feed for ruminants was studied in vitro. Adsorption experiments on animal feed (135 and 270 mg) with initial doxycycline concentrations of 35, 75, and 150 µg/mL were performed. Desorption experiments were conducted by agitation of a predetermined mass of doxycycline-loaded animal feed in PBS, at pH = 3.0, 6.0, and 7.4, to simulate changes in the gastrointestinal tract. Antibiotic concentrations were determined by LC-MS/MS analysis. The adsorption/desorption of doxycycline was described by mathematical models. Chemisorption with strong intermolecular interactions between the active functional groups of doxycycline and the organic biomass was found. The experimental release curve comprised three sections: initial prolonged 27-30% release (pH = 6.0), followed by moderate 56-59% release (pH = 3.0), and final 63-74% release (pH = 7.4). The sigmoidal model showed a considerable role of diffusion with an initial prevalence of desorption and a decreased desorption rate thereafter. The Weibull equation revealed an initial release stage followed by a lag time section and sustained release. The study of doxycycline adsorption by the animal feed proved a maximum 80% encapsulation efficiency and revealed initial diffusion followed by chemisorption. The highest release efficiency of 74% suggests high bioavailability of doxycycline after oral administration in ruminants.