Comparative bioavailability of enrofloxacin in dogs when concealed in noncommercial morsels, either as tablet or as enrofloxacin–alginate dried beads

Abstract

Administration of enrofloxacin tablets concealed in improvised morsels to elude the unpleasant flavor of this drug is likely to diminish maximum plasma concentrations (Cmax) reached by this drug, jeopardizing treatment efficacy. To avoid this, the hypothesis that alginate dried beads containing enrofloxacin (ADBE) could modify the pharmacokinetics of enrofloxacin in dogs was tested. ADBE were manufactured and pharmaceutically defined as having high entrapment efficiency (>90%) and a drug loading capacity of 56%–67%. Based on the hydrophilic nature of alginate and its interaction with the anionic charge of the amino groups of enrofloxacin, a novel modified release system was obtained in which ADBE give place to both a rapid diffusion releasing of enrofloxacin and a maintained release. The ADBE concealed in a sausage (ADBEs) achieved both the highest Cmax (5.1 µg/ml ± 0.3 SD) and the area under the concentration versus time (AUC0–24) (41.2 µg hr−1 ml−1 ± 6.9 SD). The tablet administered alone had a Cmax of 1.9 µg/ml ± 0.3 SD and an AUC0–24 = 16.5 µg h−1 ml−1 ± 3.5 SD, while the tablet concealed in a sausage reached a Cmax of 1.2 µg/ml ± 0.3 SD with an AUC0–24 = 12.3 µg hr−1 ml−1 ± 3.8 SD (p < .05 in both cases when confronting ADBEs vs. tablets). Consequently, Cmax/MIC and AUC0–24/MIC ratios are higher for ADBEs. Other PK parameters were statistically indistinguishable, and other morsels containing enrofloxacin as a tablet or as ADBE rendered less favorable PK parameters. Due to ease of administration and favorable PK for ADBE concealed in a sausage, this pharmaceutical design can be regarded as PK/PD consistent and worthy of clinical studies.

Pharmaceutical characterization and pharmacokinetics of florfenicol-loaded alginate dried beads in rabbits

“…Alginate hydrogels for drug delivery systems can be formulated in several physical forms such as microparticles, nanoparticles, films and beads (Lupo et al, 2015;Arriagada et al, 2019;Zhang et al, 2020). The air-dried alginate beads were prepared using the method according to Gutierrez et al (2020) based on a combination of extrusion and ionic gel formation, where a florfenicol/alginate solution is dropped using a syringe into a CaCl 2 solution under gentle stirring. The beads are formed immediately as ionic induced gelation occurs.…”

“…The beads are formed immediately as ionic induced gelation occurs. Alginate thus forms the polymeric matrix, trapping the florfenicol inside (Lupo et al, 2015;Gutierrez et al, 2020). Florfenicol has been formulated in several drug delivery systems for veterinary medicine such as chitosan nanoparticles, solid lipid nanoparticles and silica nanoparticles (Li et al, 2016;Karp et al, 2019;Youssef et al, 2019).…”

“…Florfenicol has been formulated in several drug delivery systems for veterinary medicine such as chitosan nanoparticles, solid lipid nanoparticles and silica nanoparticles (Li et al, 2016;Karp et al, 2019;Youssef et al, 2019). However, alginate beads have been demonstrated to be an easy and low-cost method to prepare a controlled release delivery system (Tønnesen and Karlsen, 2002;Gutierrez et al, 2020).…”

Evaluation of a Tasteless Enrofloxacin Pharmaceutical Preparation for Cats. Naive Pooled-Sample Approach to Study Its Pharmacokinetics

“…Alginate-dried beads of enrofloxacin were manufactured as previously described [ 12 ]. Thus, 2.5 mg of enrofloxacin are contained in each bead and cats were dosed with 10 mg/kg of enrofloxacin; hence, a 4 kg cat will need 16 beads per day in a single dose.…”

“…Recently, it was shown that the pharmaceutical preparation of dried-alginate beads of enrofloxacin (DABE) concealed in a morsel resulted in both adequate pharmacokinetic (PK) parameters and PK/PD ratios in dogs. It appears that these beads are tasteless to dogs, and can be concealed in morsels such as a piece of sausage or pate, without affecting its pharmacokinetics [ 12 ]. In the case of cats, it could be useful to define the pharmacokinetics of DABE when included in the moist canned commercial food for cats or morsels.…”