Pharmacokinetic Studies With Tilmicosinsustained-release Enteric-coated Powder In Piglets And The Establishment Of In Vitro/in Vivo Correlations

The dissolution test of sustained-release enteric-coated and premix were performed in compliance with Chinese Veterinary Pharmacopoeia using apparatus 1?baskets?at100r/min,selecting pH1.2 HC l,pH4.1 acetate buffer,pH6.8 phosphate buffer,with Tween-80?2%?and water withlauryl sodium sulfate?0.2%?.The dissolution sampes withdrawn from the dissolution medium were detected by UV spectrophotometric methods.Cumulativereleasewerecomputedandkineticsofdrugreleasefor Tilmicosinsustained-release enteric-coated powder was described by zero-order model.First-order model and Higuchi model using Origin Pro9.0.Results showed that the cumulative release of the premix in different dissolution medium reached 96.4⁹8.6%in 1h.However,the sustained-release enteric-coated powder in different dissolution medium reached 93.3⁹8.1%in 8h,but in pH1.2HC l solution can notreleasefull.The Pharmacokinetic studied with 18 healthy pigs.The pigs were divided into two groups randomly,9pigs in each group.The first group received Tilmicosinsustained-release enteric-coated powder and the second group receivedpremix,at the 20mg of active ingredient per kg bodyweight respectively.Thesustained-release enteric-coated powder and the premix containing 20%of Tilmicosin were administered to pigs directly by stomach tube.The plasma samples extracted were detected with high performance liquid chromatography?HPLC?and the plasma conc entration-time data were fitted with the non compartmental model by Winnonlin5.2.1.Afterreceiving a single oral dose of Tilmicosinsustained-release enteric-coated powder,the Kel was 0.171±0.0221/h,t_1/2 was 4.093±0.436h,T_max was 3.889±0.928h,C_max was1.03±0.061?g/mL,AUC was 13.264±1.627 h·?g/mL.And after receiving a single oral dose of Tilmicosin premix,the main pharmacokinetic parameters of pigs were,the the Kel was0.219±0.0421/h,t_1/2 was 3.285±0.731h,T_max was2.333±0.5h,C_max was 1.251±0.211?g/mL,AUC was 8.751±2.595 h·?g/mL.The maximum blood level and the absolute bioavailabillity after administration of Tilmicosinsustained-release enteric-coated powder are lower than after administration of premix.A comparison of the pharmacokinetic parameters reveals that the sustained-release enteric-coated powder can decrease and delay absorption of the active ingredient.It indicates that Tilmicosinsustained-release enteric-coated powder may be more secure and plays a better role in the gut than the premix.From the dissolution test,it was seen that a Level A IVIVC,which is generally linear and represents a point-to-point relationship between in vitro dissolution and in vivo input rate was existing.Compared thecorrelation coefficient,it seems the water withlauryl sodium sulfate is the best.