title: Preparation, characterization and pharmacokinetics of doxycycline hydrochloride and florfenicol polyvinylpyrroliddone microparticle entrapped with hydroxypropyl-β-cyclodextrin inclusion complexes suspension.
abstract: In order to effectively control the bacterial pneumonia in pigs, doxycycline hydrochloride (DoxHcl) and florfenicol (FF) microparticle suspension together with inclusion complexes was prepared by using hydroxypropyl-β-cyclodextrin (HP-β-CD) as host molecules, polyvinylpyrroliddone (PVP) as polymer carriers and hydroxypropyl methyl cellulose (HPMC) as suspending agents. In vitro antibacterial activity, properties, stability and pharmacokinetics of the suspension were studied. The results demonstrated that DoxHcl and FF had a synergistic or additive antibacterial activity against Streptococcus suis, Actinobacillus pleuropneumoniae and Haemophilus parasuis. The size, polydispersity index and zeta potential of microparticles were 1.46 ± 0.06 μm, 0.30 ± 0.02 and 1.53 ± 0.04 mV, respectively. The encapsulation efficiency (EE) of DoxHcl and FF was 45.28% ± 3.30% and 89.69% ± 2.71%, respectively. The re-dispersed time and sedimentation rate of the suspension were 1 min and 1. The suspension went through the 9-gage needle smoothly with withdrawal volume of 9.12 ± 0.87 mL/min. The suspension showed good stability when stored away from light, no irritation at the injection site and sustained release in PBS buffer. After intramuscular administration to pig, DoxHcl and FF could maintain over 0.15 μg/mL for 72 h. Compared to the control injection, the suspension increased the elimination half-life (T½ke) as well as mean residence time (MRT) of DoxHcl from 5.73 to 9.77 h and from 12.02 to 18.81 h, and those of FF from 12.02 to 26.19 h and from 12.02 to 28.16 h, respectively. The suspension increased the bioavailability of DoxHcl and FF by 1.74 and 1.13-fold, respectively. These results suggest that the compound suspension is a promising formulation for pig pneumonia therapy.
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (HZAU), Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Xianqiang
authors.initials: X
authors.lastname: Li
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (HZAU), Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Shuyu
authors.initials: S
authors.lastname: Xie
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (HZAU), Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Yuanhu
authors.initials: Y
authors.lastname: Pan
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (HZAU), Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Qu
authors.affiliation: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Tao
authors.affiliation: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Chen
authors.affiliation: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Lingli
authors.initials: L
authors.lastname: Huang
authors.affiliation: MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China; MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Zhenli
authors.initials: Z
authors.lastname: Liu
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (HZAU), Huazhong Agricultural University, Wuhan, Hubei 430070, China; MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China. Electronic address: wangyulian@mail.hzau.edu.cn.
authors.forename: Yulian
authors.initials: Y
authors.lastname: Wang
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (HZAU), Huazhong Agricultural University, Wuhan, Hubei 430070, China; MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China; MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China. Electronic address: yuan5802@mail.hzau.edu.cn.
authors.forename: Zonghui
authors.initials: Z
authors.lastname: Yuan
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D016977:Actinobacillus pleuropneumoniae / Q000187:drug effects; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D019540:Area Under Curve; D004318:Doxycycline / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D004339:Drug Compounding; D065546:Drug Liberation; D005260:Female; D044137:Haemophilus parasuis / Q000187:drug effects; D008297:Male; D008657:Metabolic Clearance Rate; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011205:Povidone / Q000737:chemistry*; D017011:Streptococcus suis / Q000187:drug effects; D013535:Suspensions / Q000737:chemistry*; D013552:Swine; D013839:Thiamphenicol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D013535:Suspensions; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C035534:florfenicol; D013839:Thiamphenicol; D011205:Povidone; D004318:Doxycycline
keywords: Doxycycline hydrochloride; Florfenicol; Inclusion complexes; Microparticles; Pharmacokinetics