Chitosan Modified As Pharmaceutical Excipients

In this wok, with N-phthaloyl chitosan, as a intermediate, a series of various modification reactions regioselectively was used for synthesizing 3-0-actyl-N-phthaloylchitosan(AC-Pht-CTS). New chitosan dervatives(CTS 18,CTS16,CTS5) are synthesized by the O-Acylation of 3-O-acetyl-N-phthaloylchitosan with various acyl chlorides :pentyl chloride, palmityl chloride and steartyl chloride. The products were characterized with IR and NMR spectroscopy. In compared to the starting chitosan ,the modified chitosan derivatives exhibited an improved solubility in many organic solvents.Then, the physico-chemical properties of modified chitosans(MC) were investigated. Compressibility of different length of side chain MC(CTS5,CTS16,CTS18) was studied at routine condition. All of them could be formulated into tablet. Because of their hydrophobicity, they were used as inert matrice materials for oral controlled release tablets. Venlafaxine hydrochloride(VH) was chosen as a model drug,which is easily soluble. Analytical method in vitro drug release was established. Effect of length of side chain ,drug loading and hardness for preparing tablets on the release behavior of VH was studied. The three types of MC can retard the drug release. Tablets containing CTS18 with 25% drug loading sustained drug release for 24h. The result indicated that the matrix effect of CTS18 was superior to other blocking agents, such as EC,HPMC and octadecanol. The influence of chitosan and intermediate on the drug release was also studied. Neither of them showed retarding effect on drug release. The drug released completely within 1h. MC can be used as a novel sustained release excipient to control drug release with or without other excipients.The experimental results show that modified chitosans can either be used as pharmaceutical excipient alone ,or be used to mix with other pharmaceutical excipients,own to their good workability and retarded ability.