ABSTRACT
OBJECTIVE： To establish a method for blood concentration determination of Fentanyl buccal tablet in Beagle dogs， and to study its pharmacokinetics. METHODS： A total of 6 Beagle dogs were given Fentanyl buccal tablet 1 tablet （675 μg/tablet， buccally）. The blood samples were collected 2， 5， 10， 15， 30， 45， 60， 90， 120， 240， 360， 480， 720 min after administration. After precipitated by methanol， LC-MS/MS method [the determination was performed on Agilent C18 column with mobile phase consisted of methanol-0.02％ formic acid aqueous solution （95 ∶ 5， V/V） at the flow rate of 0.5 mL/min. The sample size was 5 μL and the column temperature was 30 ℃. Mass spectrometric conditions： electrospray ionization source in the multiple reaction monitoring mode was used to detect ions， fentanyl citrate： m/z 337.1→188.0； carbamazepine （internal standand）： m/z 237.1→194.1] was used to determine the blood concentration of fentanyl citrate； the pharmacokinetic parameters were calculated by using DAS 2.0 software. RESULTS： The linear range of fentanyl citrate were 1.0-325.0 ng/mL（r＝0.998）； inter-day RSDs of precision test were lower than 5％ （n＝6）， and intra-day RSDs were lower than 6％ （n＝3）； average recoveries were （94.65±6.32）％-（99.21±3.24）％ （n＝6）. RSDs of matrix effect was lower than 15％ （n＝6）； RE of stability tests were within ±6.2％ （n＝3）. The pharmacokinetic parameters of Fentanyl buccal tablet in Beagle dogs included that tmax was （32.5±6.1） min； t1/2 was （211.8±47.4） min； cmax was （40.3±1.9） ng/mL； CLz/F was （0.006±0.001） L/（min·kg）； AUC0-720 min was （7 564.0±1 576.7） ng·min/mL（n＝6）. CONCLUSIONS： The method is simple， feasible and accurate. Fentanyl buccal tablet have good fast-release and slow-release biphasic release characteristics in Beagle dogs.
ABSTRACT
Objective:To construct double-layered controlled release system containing SDF-1 and rhBMP-2 molecules and to study the release profile of the system in vitro.Methods:The polylactic acid/chitosan(PLA/CS)nanoparticles were prepared with “emulsification-solution evaporation method”,the preparation parameters were determined by orthogonal test design.The particle size was observed by nanoparticle size analyzer,the morphology of the nanoparticles was observed with electron microscope.Then rhBMP-2 and SDF-1 were loaded into the nanoparticles in the process of emulsification,the loading efficiency and encapsulation efficiency were calculated and in vitro release was observed.Results:The double-layer nanoparticles showed spherical geometry,smooth surface and complete separation. The average particle size of the nanoparticles was (542.33 ±14.38)nm;The drug loading and incorporation efficiency of rhBMP-2 were (82.41 ±1.05)% and (24.67 ±0.43)ng/mg,those of rhBMP-2 were (75.58 ±0.84)% and (22.63 ±0.41)ng/mg,respectively. The release time of the drug from the system sustained over at least 30 days,the release profile of both drugs showed “biphasic release”. The cumulative release rate of SDF-1 and rhBMP-2 was 72.85% and 91.01% in 30 days respectively.Conclusion:The SDF-1 and rh-BMP-2 loaded PLA/CS nanoparticles have excellent morphology,high entrapment and good sustained-release in vitro.