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

Abstract

Florfenicol (FF) is a novel animal-specific amidohydrin broad-spectrum antibiotic. However, its aqueous solubility is extremely poor, far below the effective dose required for veterinary clinic. Thus, FF is often used in large doses, which significantly limits its preparation and application. To overcome these shortcomings, the FF-hydroxypropyl-β-cyclodextrin (FF-HP-β-CD) inclusion complexes were developed using the solution-stirring method. The physical properties of FF-HP-β-CD were characterized. A comparison was conducted between FF and FF-HP-β-CD freeze-dried powder injection of their muscle irritation and the pharmacokinetics. The drug loading and saturated solubility of FF-HP-β-CD at 37 °C were 11.78% ± 0.04% and 78.93 ± 0.42 mg/mL, respectively (35.4-fold compared with FF). Results of scanning electron microscopy, differential scanning calorimetry, X-ray diffraction, and Fourier transform infrared showed that FF was entrapped in the inner cavity of HP-β-CD, and the inclusion complex formed in an amorphous state. In comparison with FF commercial injection, FF-HP-β-CD increased the elimination half-life (t1/2β), transport rate constant (K10, K12, K21), and maximum concentration (Cmax) after intramuscular injection in beagle dogs. Conversely, it decreased the distribution half-life (t1/2α), absorption rate constant (Ka), apparent volume of distribution (V1/F), and peak time (Tmax). These results suggest that FF-HP-β-CD freeze-dried powder injection is a promising formulation for clinical application.

Co‐delivery of Doxycycline, Florfenicol and Silver Nanoparticles using Alginate/Chitosan Nanocarriers

“…The XRD diffractograms of DOX-FLO@AgNPs did not show the same peaks as Doxycycline and Florfenicol, indicating that both of these drugs underwent a transition from a crystalline to an amorphous state, which may be related to the encapsulated state of DOX and FLO in the Alginate/ Chitosan nanocarrier. [52], [38] . Besides, the XRD diffractogram of DOX-FLO@AgNPs shows the characteristic diffractions of silver nanoparticles at 2θ of 38.12°, 44.38°, and 64.48°, correspond to (111), (200), and (220) crystal planes of Ag standard pattern (JCPDS no.…”

A novel and water-soluble material for coronavirus inactivation from oseltamivir in the cavity of methyl and sulfated-β-cyclodextrins through inclusion complexation

“…Thus, after making ICs, the relative content of OTV reduces the intensity of the characteristic diffraction peaks. Based on the pattern of the ICs, amorphous materials lose their crystallinity when they undergo complexation, indicating that the OTV has been encapsulated in the cavity of the CDs [44] , [45] . This revealed the OTV molecule is completely amorphized after stable hydrophobic interactions with both the CDs [46] , [47] .…”

Cyclodextrin Inclusion Complexes with Antibiotics and Antibacterial Agents as Drug-Delivery Systems—A Pharmaceutical Perspective

“…Florfenicol (FF) is approved for veterinary use only. Fan et al [ 128 ] conducted physicochemical and in vivo pharmacokinetic studies of FF/HP-β-CD complexes in a water-soluble injection. Compared to the commercial injection of FF, the HP-β-CD complex increased the solubility (35.4-fold compared to FF alone), elimination half-life, transport rate constant, and peak concentration after an intramuscular injection in beagle dogs, as well as shortened the distribution half-life, absorption rate constant, apparent volume of distribution, and peak time.…”