Construction And Evaluation Of Ranitidine Hydrochloride Oral Liquid Sustained Drug Release System

Ranitidine Hydrochloride?RH?is a second-generation H₂ receptor antagonist.which is used to treat Gastric and Duodenal Ulcer,Reflux Esophagitis and other digestive diseases such as high gastric acid secretion clinically.However,RH is slightly bitter and astringent,smelly and easily absorb moisture.In addition,RH has a short peak blood concentration in the body and rapid elimination in the body?half-life is only2 to 3 hours?,which requires multiple administrations to maintain the therapeutic concentration.And the common dosage form is a solid preparation,which is not conducive to patient compliance.Based on the above problems,this work used RH as a model drug and systematically studied the preparation of Ranitidine Hydrochloride suspension with sustained release and its drug release behavior in vitro and in vivo.This research was divided into three parts as follows:Part ? Preparation and release behavior of RH drug-resinsAn in vitro analytical method of RH was established in this chapter.The influences of resin-to-drug ratio,the type of resins,temperature and initial drug concentration on drug loading process were studied to get the optimal formulation process of bath method.In vitro release behavior of RH was evaluated and analyzed by f₂ similarity factor.Based on influencing factors,the release mechanism was investigated.And the results showed that the in vitro release of RH drug resin was a particle diffusion process.Relying on ion exchange technology alone was not enough to achieve the expected sustained release effect,so the drug resonates need to be further coated with blocking materials.Part ? Research on RH resin coating technology and prescriptionIn this chapter,surface coating method was used to preparation of the RH coated microcapsules after analyzing the appearance,particle size and ease of preparation of the coated microcapsules.The effects of drug-loading,types and dosages of blocking materials,volume of reaction medium and temperature on the in vitro release of RH resin microcapsule composites were investigated using single-factor experiments and BBD-RSM experiments were used to further optimize the formulation process.The optimized RH-coated microcapsules have good reproducibility and obvious slow-release effect.Part ? Preparation and pharmacokinetics in rats of RH sustained-release suspensionsIn this chapter,redispersibility and sedimentation volume ratio were used as indicators to investigate the optimal formulation process of RH sustained-release suspensions.The factor tests and accelerated tests showed that the stability of self-made suspensions was good.The analytical methods for RH rats were established by HPLC.RH common tablets were used as a control group and self-made RH suspensions were used as an experimental group for intragastric administration.Pharmacokinetic parameters were calculated based on a non-compartment model.The results show that the C_maxax of the self-made RH suspension is lower than that of ordinary tablets,and the T_max,t_1/2 were prolonged.AUC_0-24?tablet?=22521.53 ng·h·mL^-1,AUC_0-24?suspension?=22757.71 ng·h·mL^-1,indicating that the self-made RH suspension has a stable blood concentration and sustained-release effect,and is biologically equivalent to RH ordinary tablets.