Roxatidine Acetate Hydrochloride Pulsatile Delayed-release Tablets Preparation And In Vivo And In Vitro Release Study

Objective:This study use modern theory and methods of formulation technology to develop Roxatidine Acetate Hydrochloride（ROX）pulsed delayed release tablets.To investigate the absorption characteristics of the drug in the rat small intestine;study the absorption characteristics of the drug in the intestine of rats;optimize the formulation of the best preparation and establish a method for the determination of the content of the drug;a preliminary study on pharmacokinetics in rabbits was carried out to provide a basic reference for the development of new formulations of rosatidine acetate.To provide new ideas for the development of the treatment of peptic ulcer disease,which is more in line with the needs of modern medicine.Methods:1.Study on Intestinal Absorption of Roxacitin Hydrochloride Acetate in RatsAccording to the characteristics of rat’s small intestine’s physiological condition and human beings,rat intestinal circulation was used to change the drug concentration and different intestinal segments.The absorption of rothetidine hydrochloride in the small intestine of rats was investigated.The absorption coefficient of different intestinal segments was analyzed by SPSS software.A UV dual wavelength method was established to determine the content of Roxatidine acetate hydrochlorid and phenol red in circulating fluids.2.Preparation process and prescription study of the pulse delay-release tablets of roxidine hydrochlorideAccording to the"Chinese Pharmacopoeia"2015 edition of the four general rules to determine the in vitro release of the preparation of the determination method,and the development of in vitro drug release behavior evaluation methods.The prescription of the core was determined by single factor experiment.The appropriate dissolution conditions were determined by investigate that effect of dissolution medium,dissolution method and different rotation speed on release behavior of burst release.Powder direct compression method was adopted.On the basis of the single factor investigation of various auxiliary materials,the article use the Central composite design-Response surface methodology combined with the overall desirability to optimize the formulation,and formulates the best formulation.The release homogeneity and reproducibility were investigated by using the similar factor method.3.Determination of Roxacitin Hydrochloride Acetate pulse delayed release tablets by HPLCA method for the determination of HPLC content of Roxatidine acetate hydrochlorid pulse delayed release tablets.4.Preliminary study on pharmacokineticsEach of the family’s rabbits was given a hydrochloric acid and a regular tablet and a pulse,and it set up HPLC to determine the concentration of the blood drug in the family rabbit;The pharmacokinetic parameters of rosattidine hydrochloride pulse late release tablets in rabbits were analyzed using DAS2.1.1software,and compare them with each other.Results:1.Roxacitin Hydrochloride Acetate in different concentration of hydrochloric acid absorption rate constant,there was no significant difference in different intestinal segments,the absorption rate constant has significant differences between the absorption percentage order for duodenal>jejunum>ileum>colon;The absorption of rosattidine hydrochloride in the small intestine of rats was a first order kinetic process,and the absorption mechanism was passive diffusion.2.In this paper,the method of determination of the release degree in vitro was determined,and the basic conditions for the selection and optimization of the prescription of delayed release tablets were provided.The prescription of the tablet core was ROX（75 mg）,CMS-Na（3%）,CC-Na（2%）,micro silica gel（0.5%）,and then added to 90 mg with dosage.Measured by determining the rotating basket method,900ml phosphate buffer pH6.8 to release hydrochloric acid medium to release roxatidine acetate pulsed delayed release tablets,temperature controlled at 37℃±0.5℃,speed of 100r/min.Preferred Best total weight of the coating formulation pulse 400 mg,wherein the amount of HPMC is 164.14 mg,PVP in an amount of 67.54 mg,EC dosage 126.67mg,the amount of lactose 41.67 mg,0.8374 OD value prediction.The similarity factor values of release uniformity and process reproducibility all satisfy 50≤?₂≤100.3.The HPLC method for the determination of Roxacitin Hydrochloride Acetate in pulse delayed release tablets is rapid,accurate and reproducible.It provides an accurate and precise method for the quality control of the preparation.4.The pharmacokinetic studies showed that the pulsed release tablets of Roxacitin Hydrochloride Acetate were distributed in rabbits in a two-compartment model.The main pharmacokinetic parameters of the pulsed release tablets are:k_a=1.93h^-1,t_1/2（β）=0.747h,t_max=3.0h,C_max=8.7013μg/mL,AUC_0→∞=15.716μg·h/mL,MRT=3.241h.The main pharmacokinetic parameters of ordinary tablets are:k_a=11.342h^-1,t_1/2（β）=0.747h,t_max=0.75h,C_max=10.0387μg/mL,AUC_0→∞=14.148μg·h/mL,MRT=0.139h。Conclusions:In this study,the absorption characteristics of rosabatine hydrochloride acetate in rat small intestine were studied.The results showed that rosatil hydrochloride acetate absorbed well in the whole intestine of rats.Therefore,it is advisable to develop a pulse delayed release preparation with a time lag effect.The in-vitro drug release behavior and quality standards of the developed rosartan diacetate acetate pulse release meet the established requirements and have further development significance.For the preliminary study of pharmacokinetics,the pharmacokinetic parameters of pulse preparations are superior to those of common preparations.