Pharmacokinetics and bioavailability of solid dispersion formulation of tilmicosin in pigs

Abstract

Tilmicosin (TMS) is a semisynthetic macrolide antibiotic restricted to veterinary use but is only partially soluble in aqueous solutions, which limits its administration in treatments. We developed a strategy to enhance the supersaturated solubility of TMS using amorphous solid dispersion (SD). The dissolution profile shown that the dissolution rate of TMS‐SD was obviously faster than TMS. The pharmacokinetics of tilmicosin (TMS) and tilmicosin solid dispersion (TMS‐SD) in pigs after oral administration at a single dose of 50 mg/kg b.w were investigated. The tmax of TMS‐SD (2.50 hr) was 1.80 times faster than TMS (4.50 hr) (p < .05). There were no significant differences in the other PK parameters (Cmax, t1/2β, V/F, CL/F, MRT, and AUC0‐inf) (p > .05). The mean relative bioavailability of TMS‐SD compared with TMS was 140.39%, according to the AUC0‐inf values. These results demonstrated that the solid dispersion technique enhanced the bioavailability of TMS and the new formulation administered to animals via drinking water may be used as a therapeutic alternative for clinical treatments.

Qualitative risk assessment of homogeneity, stability, and residual concentrations of antimicrobials in medicated feed and drinking water in pig rearing

“…The pharmaceutical formulation of the veterinary medicinal products is also a pivotal influencing factor on the stability and homogeneity (e.g. precipitation, solubility issues) of the drinking water medication [31,50].…”

“…The homogeneity and stability of the drug in medicated feed and medicated drinking water must be assured until the moment of intake by the animals. The residual concentrations or in other words the remaining concentrations of the antimicrobial drug in feed or water after the end of treatment, and the homogeneity and stability of medicated feed and medicated drinking water is likely to be influenced by a) the methods used for preparing, transporting, and storing medicated feed and drinking water [25], b) the materials used to construct the feed and drinking water pipelines and their design [26][27][28][29], c) the number of treatment days [7], d) the pharmaceutical formulation used [30,31], and e) the cleaning protocol of the pipelines [2]. Human errors when preparing and administering the medication may also occur if the medication is prepared at the farm instead of bought from a Good Manufacturing Practices (GMP)-certified feed manufacturer [32,33].…”

Pharmacokinetic/pharmacodynamic integration of tilmicosin against Pasteurella multocida in a piglet tissue cage model

“…The absorption half-time (T 1/ka ) and elimination half-life (T 1/2kel ) of tilmicosin in healthy pigs were 2.27 h and 43.53 h after oral administration, respectively, and 1.64 h and 20.69 h in another study ( 8 , 9 ). The V d in pigs was 48.36 L/kg after a single oral administration and the V d in both sheep and cattle were 25.0 L/kg when normalized for animal body weight, indicating the extensive tissue distribution of tilmicosin ( 10 , 11 ).…”

Pharmacokinetics of tilmicosin in chicken joints based on a novel microdialysis sampling method

“…The microdialysis sampling technology determined the concentration of free drugs and provides the feasibility for the PK experiment. PK studies of tilmicosin have been reported for cows (Ziv et al, 1995), goats (Ramadan, 1997), pigs (Li et al, 2017; Zhang et al, 2021), sheep (Şahin & Yildirim, 2019), cattle (Modric et al, 1998) and chickens (Zhang, Liu, et al, 2020). However, the chicken studies focused on plasma, lung and tissues other than joints.…”