The Study Of Buspirone Hydrochloride Gastric-Floating Sustained Release Preparations And Its Release In Vitro

Objective:The study uses the theory and method of modern science and technology to develop buspirone hydrochloride?BH?gastric-floating sustained release preparation.This thesis studied the Preparation Processin?Determination?Release mechanism and characteristics in vitro buspirone hydrochloride gastric-floating sustained release tablets and capsules.The optimal formulation was selected and the determination method was established as the basis for further research on the new dosage form of buspirone hydrochloride.Based on the existing common tablets of buspirone hydrochloride,This study lays a foundation for the further study of new dosage forms of buspirone hydrochloride and provides a safe,stable and efficient new preparation for the treatment of generalized anxiety disorder.Methods:1.Study on formulation and preparation processAccording 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.Taking the cumulative release percentage of buspirone hydrochloride gastric-floating sustained release preparation as the index,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.And the floating performance of the gastric-floating preparation was investigated based on the drifting and continuous bleaching time.Preliminary preparation prescription obtained by single factor test:For buspirone hydrochloride gastric-floating sustained release tablets,The viscosity and dosage of HPMC,dosage of MCC,lactose and NaHCO₃ were investigated by single factor experiment.For its sustained release capsules,The viscosity and dosage of HPMC,the dosage of MCC,lactose and NaHCO₃ were investigated by single factor experiment.Used Design-Response surface methodology to optimize the test results,and formulated the best preparation prescription finally.2.Determination of buspirone hydrochloride gastric-floating sustained release preparation by HPLCEstablish the methods of HPLC to determine the contents of buspirone hydrochloride gastric-floating sustained release preparation,and did methodological researches.3.Study on in vitro release properties of buspirone hydrochloride gastric-floating sustained release preparationZero-order release model,first-order release model,Higuchi equation and Rigter-Peppas model were used to fit the release curve of sustained-release preparations in vitro,and the release mechanism was investigated.This method aims to prepare a three-dimensional release characteristic chart of"in vitro release volume-pH-time"by fitting the in vitro release curve of the sustained release formulation.To investigate the release mechanism of sustained-release preparations and study the release properties in vivo.Results:1.The in vitro determination method of buspirone hydrochloride gastric-floating sustained release tablets and capsules was determined,and the evaluation standard for drug release of sustained-release preparations in vitro was established.The best formulation was obtained after screening the formulation by floating performance experiment,single factor experiment and Design-Response surface methodology.The formulation of buspirone hydrochloride gastric-floating sustained release tablets has a weight of about205 mg,wherein the amount of HPMC?K4M?is 70 mg,the amount of MCC is25 mg,the amount of lactose is 50 mg,and the amount of NaHCO₃ is 45 mg;The prescription tablet of the capsule weighs about 175 mg,wherein the amount of HPMC?K100M?is 100 mg,the amount of HPMC?K15M?is 35 mg,the amount of PVP is 10 mg,and the amount of cetyl alcohol is 15 mg;The capsule was prepared by loading the mixed powder into the rubber shell and then curing at elevated temperature.The similarity factor values of release uniformity and process reproducibility all satisfy 50??₂?100.2.The HPLC method for the determination of buspirone hydrochloride gastric-floating sustained release preparation is rapid,accurate and reproducible.It provides an accurate and precise method for the quality control of the preparation.3?According to the study on the in vitro release mechanism of buspirone hydrochloride gastric-floating sustained release preparation,it was determined to be non-Fick diffusion,which is caused by diffusion and skeleton dissolution.Studies on the three-dimensional release characteristics of"in vitro release volume-pH-time"showed that different pH environments have no significant effect on the release behavior of the preparation.Conclusions:In this study,the in vitro release of buspirone hydrochloride gastric-float sustained release tablets and capsules was studied.Selecting the scientific and reasonable preparation process and in vitro release conditions,and investigating the floating performance.Based on the single factor experiment,the design-response surface method is used to optimize the formulation of the preparation to obtain the best prescription for the prescription.A method for the determination of tablets was established.By fitting the release curve of preparation preparation in vitro and the three-dimensional release curve of"in vitro release volume-pH-time",the release mechanism was studied and the stability of the release behavior was confirmed.The in vitro release behavior and quality standards of the prepared gastric-floating sustained release preparations meet the established requirements.This study laid a foundation for the study of a new formulation of buspirone hydrochloride and provided a safe,stable and efficient new formulation for the treatment of generalized anxiety disorder.