Preparation Of Amoxicilin/Radix Scutellariae Extract Powder And Pharmacokinetic Study In Pigs

Amoxicillin（AMO）is aβ-lactam antibiotic with broad-spectrum antibacterial properties and is widely used in veterinary clinics for sensitive Gram-positive and Gram-negative infections;Radix Scutellariae extract（RSE）is a pale yellow powder obtained by extracting and drying Astragalus.The baicalin is the main active ingredient of the extract of Astragalus,and has pharmacological activities such as antibacterial,anti-inflammatory and anti-oxidation.In veterinary clinic,AMO and RSE were often used in combination to prevent and treat some bacterial infectious diseases.To date,there is currently no compound preparation of amoxicillin-Radix Scutellariae extract powder.Based on this,this study will evaluate amoxicillin-Radix Scutellariae extract powder from the aspects of prescription screening and process research,preliminary stability of preparation,and pharmacokinetic study in vivo,aiming to provide a safe and effective amoxicillin+RSE compound preparation for veterinary use.Firstly,the test determined the minimum inhibitory concentration（MIC）of AMO and RSE against Escherichia coli,Staphylococcus aureus and Streptococcus,and basis on this results,A combined AMO and RSE susceptibility test for Staphylococcus aureus was conducted.The results of in vitro combined drug susceptibility test showed that the extracts of AMO and RSE showed additive or synergistic effect on Staphylococcus aureus,and provided a basis theory for compound preparation.Secondly,this experiment carried out pre-prescription research:HPLC method for determination of AMO and RSE content was established respectively;the equilibrium solubility and oil-water partition coefficient of amoxicillin and Radix Scutellariae extract were investigated;and the compatibility of AMO and RSE was studied.The results showed that the established AMO and RSE HPLC methods were accurate and reliable,and could be used for the determination of AMO and RSE.The solubility of AMO increased with the increase of p H（except p H=1）.The solubility of RSE also increased with increasing p H.The P_appvalues of AMO and RSE in water/n-octanol with p H values of1.0,5.8,6.8,7.2 and 7.4 were 51.97,0.13,0.24,0.31,0.18 and 5.36,1.32,0.01,0.08,0.06,respectively.Lg P_appvalues were 1.72,-0.89,-0.62,-0.51,-0.75 and 0.73,0.12,-1.85,-1.08,-1.24,respectively.It indicated that AMO and RSE were well absorbed in the gastrointestinal tract.After mixing with AMO and RSE for 10 days after high temperature,high humidity and strong light irradiation test,there was no obvious change in the traits,appearance uniformity,moisture,related substances and content of AMO,indicated that they were compatible.Pre-prescription research provided the foundation for prescription design and pharmaceutical research.Thirdly,after completed the pre-prescription study,this experiment carried out the prescription screening study of the amoxicillin-radix scutellariae extract powder.The relative density of the original and auxiliary materials,the relative moisture absorption rate and the angle of repose were taken as indicators.The critical relative moisture absorption of the compound powder was carried out.Determination of degree,appearance uniformity,moisture and content.Screening results showed the glucose was used as the auxiliary material.The reasonable ratio was AMO:RSE:glucose=10:5:85.The compound powder was prepared by mixing process.In this experiment,the preliminary stability study of amoxicillin-radix scutellariae extract powder was carried out with reference to the 2015 edition of the Chinese Veterinary Pharmacopoeia,including strong light irradiation test,accelerated test and long-term test.The results showed that the light,humidity and temperaturehad little effect on the stability of the active ingredients in the compound,indicating the product should be kept under cool and dark place.Finally,the amoxicillin-radix scutellariae extract powder was examined for pharmacokinetics in the target animal（pig）.HPLC analysis methods for determination of AMO and baicalin（BCL）in pig plasma were established.The specificity,linearity,recovery and precision of the method met the requirements of pharmacokinetic analysis methods.The blood drug data were analyzed and processed,and the main parameters of pharmacokinetics were calculated using the non-compartment model statistical moment theory.Results of the main parameters of AMO in amoxicillin-radix scutellariae extract powder and amoxicillin powder were as follows:C_maxwas（0.94±0.25）μg/m L and（0.92±0.14）μg/m L,and T_maxwas（1.0-2.0）h and（1.0-1.5）h,AUC is（4.12±0.96）μg·h/m L and（4.35±1.64）μg·h/m L,t_1/2λis（6.04±3.98）h and（3.97±1.76）h,MRT was（7.99±4.37）h and（5.88±2.07）h.The main pharmacokinetic parameters of BCL in amoxicillin-radix scutellariae extract powder and single radix scutellariae extract powder were as follows:C_maxwas（0.63±0.22）μg/m L and（0.73±0.34）μg/m L,and T_maxwas（0.33-4.00）h and（0.33-2.00）h,AUC is（4.6.97±1.69）μg·h/m L and（5.35±1.45）μg·h/m L,t_1/2λis（7.61±2.92）h and（9.21±3.75）h,MRT is（11.52±3.77）h and（12.43±5.04）h.Compared with the single amoxicillin powder,the t_1/2λand MRT of AMO in the amoxicillin-radix scutellariae extract powder were prolonged,but the difference was not statistically significant（P>0.05）.Other main pharmacokinetic parameters AUC,C_maxand AUMC was not significant（P>0.05）.Compared with the RSE powder,the pharmacokinetic parameters AUC of BCL in amoxicillin-radix scutellariae extract powder was larger than that of unilateral,but the difference was not significant（P>0.05）.The other major pharmacokinetic parameters,such as t_1/2λ,MRT,C_max,AUMC were also not significant（P>0.05）.The results showed that after oral administration of amoxicillin-radix scutellariae extract powder,the amoxicillin and radix scutellariae extract powders did not affect each other’s pharmacokinetic behavior.In conclusion,an amoxicillin-radix scutellariae extract powder was developed,and the preliminary stability and the pharmacokinetic in vivo of the compound preparation were to be investigated and further provide a scientific foundation for further studies.