Study On NaCS Used For Vegetable Capsule And Colon-targeted Drug Delivery Capsule

With the development of technology, more and more progress was made in pharmaceutics. Excipient is indispensable to the production of drugs. Excellent excipient will be decisive of the way of drug delivery, such as delayed release, controlled release, targeted release and so on. In a sense, the development of a new excellent excipient is more important to the development of new drugs. In various dosage forms, capsule became the main form for oral solid drugs due to its advantages such as high bio-utility, stabilization for drugs, time controlled release and targeted release, etc. The main materials of capsule are gelatin. The application of gelatin capsule is limited because it comes from animals. Thus, the development of new materials from non-animal recently is focused on. Among the various colon-targeted drug delivery systems (CSDDS), the bacteria-releasing enzymes triggered drug delivery system is investigated widely at home and abroad due to its excellent site-specific property. In this work, a novel biomaterial--- sodium cellulose sulfate (NaCS) was applied to vegetable capsule and colon-targeted drug delivery capsule (CTDDC). The determination of NaCS molar weight (Mw), NaCS mechanical properties, capsule characteristics (brittleness, degradation, drug release, pharmacal stabilization), the optimization of preparation of vegetable capsule and CTDDC and the degradation experimentation of capsules in various simulated fluids were respectively investigated.Firstly, the method of NaCS Mw determination by using low angle laser light scattering was established. The effects of different salts and their concentrations on Mw determination were also investigated. When the concentration of salts was in the range of 0.05-0.075mol/L, the accuracy of determination was better. However, when the concentration of salts was lower than 0.05mol/L, the accurate results were obtained hardly.Secondly, The relationship between NaCS film mechanical properties and NaCS Mw, NaCS DS, NaCS added different materials were studied. The mechanical properties of NaCS film were significantly influenced by NaCS Mw, however, were less influenced by NaCS DS. The tensile strength and elongation at break would decrease when carrageenan or agar was added in NaCS film. The tensile strength of NaCS-chitosan film was smaller than NaCS film, and on the contrary, the elongation at break of NaCS-chitosan film was bigger than NaCS film. The mechanical properties of NaCS-chitosan-gelatin film were similar to gelatin film. The brittleness of NaCS capsule from NaCS film with better mechanical properties was less than that with worse mechanical properties.Thirdly, the preparation of vegetable capsule based on NaCS and capsule characteristics were investigated with the dipping temperature, concentration of carrageenan, concentration of NaCS, NaCS DS and NaCS Mw. The optimum preparation condition was that the dipping temperature was 45～65℃, concentration of carrageenan was 1.5～2.0%(w/v), concentration of NaCS was 3.0～4.0%(w/v). The characteristics of NaCS capsule were advantaged over those of gelatin capsule and similar to Vcaps produced by Pfizer Pharmaceuticals Limited. In vitro drug release of 5-ASA from capsules based on NaCS was determined.5-ASA could be released completely within 15min.Fourthly, a novel polyelectrolyte complex (PEC) formed by NaCS and chitosan was prepared as a potential material for the colon-targeted drug delivery system. The characteristics of NaCS-chitosan film were measured by the scanning electron microscopy (SEM), fourier transform infrared spectrometer (FTIR), in vitro degradation and in vitro drug release experiments. In vitro degradation behavior revealed that NaCS-chitosan could be degraded by colon microflora, and could not be hydrolyzed in the water solution, the simulated gastric fluid (SGF) and the simulated intestinal fluid (SIF). The degradation characteristics of NaCS-chitosan film in the simulated colonic fluid (SCF) were significantly influenced by NaCS DS, however, were less influenced by NaCS Mw. NaCS-chitosan-gelatin film could be hydrolyzed in the SGF and SIF, but could not in the SCF. This phenomenon indicated that the degradation characteristics of NaCS-chitosan-gelatin film were decided by those of NaCS-chitosan film. Finally, the preparation of NaCS-chitosan complex was optimized by using response surface methodology to evaluate the effects of these parameters (NaCS DS, concentration of NaCS, viscosity of chitosan, concentration of chitosan) on the degradation characteristics of NaCS-chitosan in the SCF. A mathematical model was established to describe the effect of these parameters and their interactions on the degradation characteristics of NaCS-chitosan complex. It was found in the experiment of in vitro drug release that the capsules formed by NaCS-chitosan complex could release about 80% drug (5-ASA) loaded in the SCF during 4 hrs. The brittleness and water content of colon-targeted drug delivery capsule were similar to gelatin capsule. The results of pharmacal stabilization experiment indicated that the capsule still had better characteristics of drug release after accelerated tests of three months.All these results indicated that NaCS film could be used for vegetable capsule due to its better mechanical properties. NaCS-chitosan complex showed the excellent behaviors of colon-targeted and could be a potential material for the colon-targeted drug delivery system.