| Isoperidone Hydrochloric Acid is a novel compound synthetized by our laboratory,with independent intellectual property rights..The Isoperidone hydrochloric acid is a prodrug of paliperidone,which one is new antipsychotic drug.After oral administration,Isoperidone Hydrochloric Acid can be rapidly and completely metabolized in vivo to poliperidone.Chitosan(CS)is a cationic polymer.And it has been identified as a useful component for tablets,which can produce Polyelectrolyte complex(PEC)with Anions.According to the previous research,PEC-based matrix tablets might avoid the utilization of covalent crosslinking reagents since the crosslinking occurred by ionic linkage,and also reduces the swelling and erosion of the matrix,thereby,extending drug release.The drug’s release can be extended to more than 24 hours by the matrix tablet,which plays an important role in the treatment of schizophrenia.In this study,we established an analysis method in vitro by high performance liquid chromatography(HPLC)for Isoperidone Hydrochloric Acid.And verified the feasibility of the method by accuracy,precision and specificity.Then we evaluated the Isoperidone Hydrochloric Acid in the content uniformity,stability,dissolution in vitro and.Then in vitro release as the evalution standard,we made the prescription screening of tablets,choosing the type of anion and the ratio of anions to chitosan as the investigation factor.Finally,beagle dogs were selected as the animal model,and the tablets prepared by the optimal prescription were analyzed by pharmacokinetic analysis in vivo,the method of treating plasma samples and the decection conditions were also determined.We finally adapted the wet granulation craft to produce the tablets with chitosan(cation)and xanthan(anion)at the ratio of 1:1.Each tablet contains 1.5mg drug.The pharmacokinetic parameters as follows: t1/2: 8.14±0.95 h;Cmax: 273.84±13.16μg/L。The tablet prepared in this study showed good release characteristic,which are able to achieve the purpose of continuously releasing in 24 h,and the in vivo’s results responded to the in vitro.Results of the in vivo pharmacokinetics demonstrated that thetablet have high area under the curve(AUV).The drug release curve obtained by this study is more smooth,which is of great significance to reduce drug release prolong drug release time and reduce drug side effects.PEC polyelectrolyte polymers used in preparation of tablets in this study showed good characteristics.According to the characteristic that chitosan and anions can be self-assembled in the gastrointestinal environment to form the PEC film,we can prepare the tablets with a core-shell structure by simple mixing to impore the drug release,which study provides an available idea and reference for preparing the release agent which have small burst effect and uniform release curve tablet with good characteristics in future. |
