Controlled Release Of Hydrogels Based On Cross - Linked Carboxymethyl Chitin - Based Intelligent Drugs

In this paper, the drug loaded hydrogels were prepared from a series of carboxymethyl chitin(CMCH) with high degree of substitution(DS) and different degree of deacetylation(DD) as the drug carrier, aspirin as a model drug, and glutaraldehyde as a crosslinking reagent. The drug loaded particles were prepared respectively by freeze-drying and oven drying for drying the hydrogel, and their drug release was measured with rotating basket method. The effects of DD of CMCH, dosage of glutaraldehyde and drying method on drug release property of drug loaded particles were researched.CMCH with high DS(120%) and low DD(18%) was prepared from chitin, and the molar ratio of chitin repeat unit, Cl CH2 COOH, and Na OH was 1: 3.5: 7.5. The chitin powder was dissolved in 23%(wt. %) of Na OH solution and reacted 4 h at 60 ℃. A series of CMCHs with high DS and different DD were prepared by the deacetylation of above CMCH with different concentration of Na OH solution, reaction temperature and time. And these CMCHs were characterized with elemental analysis(EA), potentiometric titration, thermal analysis(TGA), X-ray powder diffraction(XRD), fourier transform infrared spectroscopy(FTIR) and proton nuclear magnetic resonance(1H NMR) methods. The results showed that the DS of a series of CMCHs was similar(120%), while the DD was 18%, 23%, 30%, 48%, 51%, 63%, 71% and 80%, respectively. The thermal stability of CMCH decreased as the DD increased, but the thermal decomposition temperature of all CMCHs was higher than 200 ℃.The drug loaded hydrogels were prepared from 0.2 g of CMCH(DD=18%, 51%, 80%) as a carrier, aspirin as a model drug and 1% of glutaraldehyde solution(1.5 m L, 2.0 m L) as a crosslinking reagent. The drug loaded particles were prepared by freeze-drying for drying the hydrogel, and their drug release profile in simulated gastrointestinal fluids was tested with rotating basket method. The results showed that the hydrogel prepared by adding 2.0 m L, 1% of glutaraldehyde solutin represented high crosslinking density, was not conducive to swelling and was less released regardless of DD. While the hydrogel prepared by adding 1.5 m L, 1% of glutaraldehyde solution was more appropriate for drug release.The drug loaded hydrogels were prepared from 0.2 g of CMCH with different DD as a drug carrier, aspirin as a model drug, and 1% of glutaraldehyde solution(1.5 m L) as a crosslinking reagent. The drug loaded particles were prepared respectively by freeze-drying and oven drying for drying the hydrogel, their appearance was characterized by SEM morphology, and their drug release was measured with rotating basket method. The results showed that the drug loaded particles prepared from CMCH(DD=51%) expressed a porous three-dimensional network structure, and the pore size was about 50~100μm(with oven drying) and 100~150 μ m(with freeze-drying). The drug release rate in simulated gastrointestinal fluid of drug loaded particles prepared by freeze-drying increased as DD increased, but showed abnormal while DD=18% and 51%. The drug release rate in simulated gastrointestinal fluid of drug loaded particles prepared by oven drying was the highest while DD=51%, increased as DD increased(DD<51%), decreased as DD increased(DD>51%), but showed abnormal while DD=18%. The drug release rate in simulated gastric medium(p H 1.0) of drug loaded particles prepared by freeze-drying was higher than that in simulated intestinal medium(p H 6.8). However, the drug release in simulated gastric medium of drug loaded particles prepared by oven drying was slow and the drug release rate was low, but the drug release in simulated intestinal medium was fast and the highest cumulative release rate was 80%.The drug loaded particles prepared from corresponding hydrogel by oven drying showed a significant p H-sensitivity and was valuable on colon drug release.