Preparation, characterization, and pharmacokinetics in swine of a florfenicol enteric formulation prepared using hot‐melt extrusion technology

Abstract

The objective of this work was to manufacture an enteric formulation of florfenicol (FF) using hot-melt extrusion (HME) technology and to evaluate its in vitro dissolution and in vivo pharmacokinetics. For the HME process, hypromellose acetate succinate LG (HPMCAS-LG) was the enteric polymer mixed with FF, and the two components were extruded with a standard screw configuration at a speed of 50 rpm. Differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FT-IR) were performed to characterize the HME extrudate. The release percentage of the enteric formulation in the acidic stage was <10% of the loaded FF, whereas that in the phosphate buffer stage was >80%. Pharmacokinetic evaluations in swine revealed that the enteric formulation had a longer t and MRT than commercially available FF powder (FULAIKA ), indicating that the novel formulation exhibited enteric and sustained release properties. Compared with the commercial product, the relative bioavailability of the enteric formulation reached up to 117.2%. This study suggests that this formulation may have potential for future commercialization.

Florfenicol Sustained-release Granules: An in Vitro release and pharmacokinetics study in pigs

“…dose of FS, the area under the concentration-time curve (AUC), elimination rate constant (K el ), the elimination half-life (T 1/2β ), mean residence time (MRT), body clearance rate (Cl), and apparent volume of distribution (V d ) were 114.97 ± 12.90 h•µg/ml, 0.21 ± 0.031 h − 1, 3.32 ± 0.50 h, 4.52 ± 0.48 h, 0.18 ± 0.020 L/h/kg, and 0.84 ± 0.095 L/kg, respectively. The T 1/2β and MRT values indicate that the drug in plasma was quickly eliminated, which was in agreement with that reported by Liu, Jiang and Xu [9,19,20]. while a signi cantly (p < 0.01) delayed T max was observed in the curve of FSRGs in fasted and fed conditions, which were 4.25 ± 1.16 h and 3.50 ± 0.53 h, respectively.…”

“…Sustained-release preparation has the advantages of sustained and slow release of drugs and reducing the uctuation of blood concentration. Over the past decade, there were a large number of researches on FFC sustained-release formulation that used nanotechnology and high-molecular compound as ingredients [8][9][10][11][12][13]. However, most of them are used for injection administration, which is less suitable for large-scale farming.…”

Comparative muscle irritation and pharmacokinetics of florfenicol-hydroxypropyl-β-cyclodextrin inclusion complex freeze-dried powder injection and florfenicol commercial injection in beagle dogs

“…Florfenicol (FF), also known as fluthiracnamline, is chemically named D(+)-threo-1-p-sulfonylphenyl-2-dichloroacetamido-3-fluoropropanol. FF is an excellent broad-spectrum antibiotic for animals with broad antibacterial spectrum, wide distribution in the body, and with safe and efficient features; particularly, it does not potentially cause aplastic anemia and without teratogenic, carcinogenic, and mutagenic effects 1 . FF is extensively used clinically for the treatment of bacterial diseases in livestock and poultry caused by susceptible strains.…”

“…The chemical methods used to increase FF solubility include the synthesis of FF phosphate, FF sulfonate, and FF succinate 1 . However, the preparation conditions of FF phosphate are reported to be complicated and are unsuitable for industrial production.…”