Synthesis And Characterization Of Poly-ε-caprolactone And Study On Buspirone Extended-release Tablet

Macromolecule materials have been acted as an indispensable factor in preparing novel drug delivery systems, such as extended-release preparations and others. And whether these materials can be used in pharmacy or not is determined by its safety and corresponding basic property. In this text, buspirone, a novel kind of anti-depression drugs, was chosen as the study object of extended-release tablet, in which poly-ε-caprolactone (PCL) and HPMC were selected as the excipients. At the same time, the synthetic methods, productivity and repetition, cytotoxicity and animal acute toxicity of PCL are studied also. It shows that the synthetic method of the PCL we taken has good repetition and high productivity and that the PCL is safety, and also the buspirone extended-release tablet has idealized drug-release behavior in vitro. The following parts comprise the study.Synthesis and characterization of PCL Ring-opening polymerization of PCL was catalyzed by Ti(OBu)4 and polymerization mixtures were prepared by introducing with a precision syringe under nitrogen atmosphere and stirring for 4 hours at 100℃. The aim product was characterized by means of GPC, FTH, NMR,DTG and XRD, and the result shows that the product has good molecular weight distribution and high productivity.Studies on the basic properties of PCL To determine the viscosity, intrinsic viscosity, thermal gravity analytics (TGA) and X-ray powder diffraction (XRD) of PCL in different molecular weight. The result shows that the viscosity, intrinsic viscosity, melting temperature, crystallinity and thermal degradable temperature of PCL are correlated with its molecular weight. In the XRD profiles, the area of peaks of PCL shows the same size.Cytotoxicity and animal acute toxicity of PCL L929 cell line was used to evaluate the cytotoxity of PCL by means of MTT and fluorescence staining method. Animal acute toxicity was performed by giving to mice with 25%PCL suspensions in one day. The result shows that PCL is safe and no toxic reaction found in cytotoxiciry experiment, also the dosage in 20g/kg given to mice in one time is safe.Study of buspirone extended-release tablet To select the suitable ratio of excipients in prescription of tablet through uniform design, also compare the tablets drug-release behavior whose excipient was PCL in different molecular weight or HPMC respectively. The result shows that the idealized ratio of excipients in buspirone extended-release tablet was gained, which has good drug-release behavior. Different molecular weight of PCL can influence the rate of drug-release, thus the larger of its molecular weight, the slower of the rate is. Compared with HPMC, PCL can reduce the rate of drug-release in buspirone extended-release tablet.