Preparation Of Adprin-?-cyclodextrin Inclusion Complex And Its Pharmacokinetics In Chickens

The characteristics of chicken coccidiosis is high morbidity and high mortality,it currently relies on drugs to control.However,the resistance of coccidiosis had been growing worse for the long-term unreasonable use of drug.So it is necessary to develop new anticoccidial drug and the adaptive form for clinical trials.Adprin is a new anti-coccidiosis medicine,which has been provided with high efficiency,broad-spectrum and low toxicity.Its pharmacological properties was similar with purine compounds-Aprinocid.There are no relevant reports about adprin preparation at domestic and foreign.?-Cyclodextrin??-CD?is a kind of oligosaccharides compound.It was widely used in medical fields as materials in recent years because of its special structure and good compatibility.Adprin-?-CD inclusion complex was successfully developed by orthogonal test,and this new dosage form was evaluated according its clinical efficacy,pharmacokinetics and toxicity on the target animal-chicken.The purpose was to provide the basis for the formulation of new drug development and guide the clinical rational use of drugsIn this study,the method to determine the content of adprin-?-CD inclusion complex by UV spectrophotometric detection was established,and the best preparation process was confirmed by orthogonal test.The inclusion complex was characterized by the means of thin layer chromatography?TLC?,phase solubility,and infrared spectrophotometry.According to requirement on "the new veterinary drug management" by the Ministry of Agriculture,this study observed the vitro dissolution and stability of complex.The main pharmacokinetic parameters and bioavailability of complex had been compared in the study of pharmacokinetics.At last,the clinical efficacy of anticoccidiosis and acute toxicity on the target animal of complex had been observed by test.Results: Content detection by UV was established,the rate of recovery was99.8%,RSD was 0.15%,the stability is 0.18%.This method is suitable for determination of adprin-?-CD inclusion complex.The best prescription was n??-CD?: n?adprin?=1.5:1;the temperature is 65?;acetic acid: water =2:8,and the stirring time is 8 h.The results of appraisal of complex shown that adprin-?-CD inclusion complex had been prepared successfully.The vitro dissolution curve showed that the release of adprin,inclusion,complex and physical mixture were all consistentwith weibull equation,and the drug dissolution rate was improved by clathration.In the stability test,the changing by appearance,moisture and content of inclusion complex changes were in line with the requirements,in the strong light,high temperature and high humidity conditions.The accelerated test and long-term test results showed that the indicators of inclusion complex had not significant changes,and had good stability.The term of validity could be set at 2years preliminarily.Blood concentration was determined by HPLC-MS/MS,and the recovery rate was 92.83%,the intra day precision was 1.33%,and the inter day precision was 1.80%.This method was applicable for the determination of adprin-?-CD inclusion complex in blood.The results of pharmacokinetic study showed that the inclusion could enhance absorption in vivo and bioavailability.In clinical curative effect test,it was confirmed that the anticoccidial effect of complex was better than that of amprolium,diclazuril and premix,solution of adprin.In toxicity test,LD₅₀ of group inclusion complex was the highest;it indicated that complex has lower toxicity and higher safety,relatively.Conclusion: preparation and detection methods of complexes had been established successfully.The vitro dissolution,solubility,bioavailability,and efficacy of adprin were improved,while the toxicity was lower relatively.The test had provided clinical drug delivery scheme of adprin,but also provide the basis for developing new dosage forms of drugs.