Preparation And Performance Study Of Clopidogrel Bisulfate—Montmorillonite Gel Beads

Clopidogrel bisulfate is a thienopyridin class antiplatelet agent. After oral administration of ordinary tablets, the burst release is obvious, therefore easy to cause adverse reactions such as gastrointestinal bleeding, diarrhea. This study decided to prepare CLP sustained-release preparation to reduce the burst release.In this thesis, clopidogrel bisulfate was intercalated into the interlayer of montmorillonite with ion-exchange, and further coated with sodium alginate to form gel beads. The CLP—MMT gel beads could avoid the burst release of clopidogrel bisulfate in simulated gastric. The gel beads can efficiently reduce adverse effects of clopidogrel bisulfate, thereby improving patients’adherence.The loading efficiency, encapsulation efficiency and cumulative release rate of CLP—MMT composite and CLP—MMT gel beads were determined by Ultraviolet absorbance at270nm. The experiment results proved that the methods were accurate, sensitive, and simple.Solution intercalation method was used to prepare CLP—MMT composite. The orthogonal experiment was carried out to select the best prescription according to the loading efficiency on the base of single-factor experiments, the prescription with initial concentration of CLP is0.25mg/mL, reaction time is1h, reaction temperature is50℃and pH value is4is the ideal, and repeat the prescription, loading efficiency could achieve (10.74±0.30)%.The CLP-MMT composites were characterized by IR, XRD, TGA and SEM. In vitro release experiments, it showed obviously burst release phenomenon by CLP tablets in simulated gastric. However, CLP-MMT composites could reduce the burst release in a certain extent.Dropping method was used to prepare CLP-MMT gel beads. The single-factor experiments was carried out according to the loading efficiency, encapsulation efficiency and cumulative release rate. The orthogonal experiment was carried out to select the best prescription according to the loading efficiency, the prescription with CLP:SA=1:3, concentration of CaCl2is0.4mol/L, concentration of SA is15mg/mL gelling time is40min is the ideal, and repeat the prescription, loading efficiency could achieve (7.66±0.20)%.The CLP-MMT gel beads were characterized by IR and SEM. In vitro release experiments, burst release phenomenon can be avoided efficiently by CLP-MMT gel beads in simulated gastric. Fitted the drug release kinetic model with the data of drug release from0hour to24hours, the reslut show that drug release macth the one order kinetics model. Evaluated the stability according to appearance, content and cumulative release rate, the results showed that the content and dissolution of CLP-MMT gel beads reduced in highlight.