Preparation And Evaluation Of Robenidine Hydrochloride Solid Dispersion

Chicken coccidiosis is one of the parasitic disease that is common and harmful in poultry breeding.Robenidine hydrochloride is one of the widely used anticoccidials.The robenidine hydrochloride solid dispersion could be administrated by drinking water,which not only increase absorption and bioavailability of the drug.This could enrich the preparation variety and facilitate the veterinary clinical administration.An analytical method for the determination of robenidine hydrochloride in vitro by ultra high performance liquid chromatography?UPLC?was established.The assay was carried out on a ACQUITY UPLC BEH C₁₈ column?1.7?m,2.1×100mm?with acetonitrile-0.2%phosphoric acid aqueous solution?V:V=40:60?as mobile phase.The results showed good separation of the main component and each impurity.The calibration curves of analytes showed good linearities within the mass concentration of 15³5?g/mL?R²=0.999?.The average recoveries of samples with low,medium and high concentrations were 100.85%,100.61%and 100.40%,and their relative standard deviation?RSD?were 1.50%?0.07%and 0.64%,respectively.The major impurities of robenidine hydrochloride were R1 and R2 with retention time of 1.61 min and 5.41 min respectively.Three-factor and three-level orthogonal test methods were used for the formulation screening and technological research.A robenidine hydrochloride solid dispersion with PVP–K 30 as carrier was successfully prepared.The robenidine hydrochloride solid dispersion prepared by rotary evaporation and spray drying were analyzed and compared.The results showed that the solid dispersion prepared by spray drying has better solubility than that prepared by rotary evaporation.The results showed that robenidine hydrochloride solid dispersions met the general requirement of the soluble powder in Chinese Veterinary Pharmacopoeia.The solubility of robenidine hydrochloride in ultrapure water were improved20 times and remained stability.DSC,XRD,FTIR and SEM showed that the robendinine hydrochloride was dispersed in the carrier in an amorphous state which greatly improved dissolution and solubility of robenidine hydrochloride.An UPLC method was established for the extraction and detection of robenidine hydrochloride from chicken plasma.The assay was carried out on a ACQUITY UPLC BEH C₁₈ column?1.7?m,2.1×100 mm?with acetonitrile-0.2%phosphoric acid aqueous solution?V:V=45:55?as mobile phase.The calibration curves of analytes showed good linearities within the mass concentration of 0.01¹?g/mL?R²=0.997?.Limit of detection and limit of quantitation were 0.005?g/mL and 0.01?g/mL respectively.The average recoveries of samples with low,medium and high concentrations were79.50%?71.81%and 66.83%,with the intra-assay coefficient of variation were from 1.76%to10.15%and the inter-assay coefficient of variation were from 8.31%to 10.41%,respectively.The method has high sensitivity and good reproducibility that can satisfy the determination of robenidine in plasmae.Pharmacokinetic studies of chicken oral administrated robenidine hydrochloride solid dispersion and API were conducted.The results showed that the C_max of the solid dispersion of robenidine hydrochloride was about 3.40 times than that of the API,and the T_max was about 1 hour earlier than API's.The relative bioavailability of the solid dispersion of robenidine hydrochloride was241.03%.The anticoccidial activity of robenidine hydrochloride solid dispersions and API at dose of 10,20,30 and 40 mg/kg feed were compared by setting up a solid dispersion drug test group,drug substance control group,infection control group and healthy control group.The results showed that the test group and the drug control group at all doses both showed high anticoccidial effect.