Anraku Makoto, Hiraga Ayumu, Iohara Daisuke, Pipkin James D, Uekama Kaneto, Hirayama Fumitoshi
Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-Ku, Kumamoto 860-0082, Japan.
New Product Development Ligand Pharmaceuticals Inc., 2029 Becker Drive, Suite 217 Lawrence, KS 66047, USA.
Int J Pharm. 2015 Jun 20;487(1-2):142-7. doi: 10.1016/j.ijpharm.2015.04.022. Epub 2015 Apr 13.
An intermolecular complex formed from a 1:1 weight ratio of chitosan (CS, molecular weight 30 kDa) and sulfobutyl ether β-cyclodextrin (SBE-β-CyD, degree of substitution 7) was less soluble than either of the original components. The release of famotidine from tablets composed of a simple mixture of CS and SBE-β-CyD is slower in media at pH 1.2 than at 6.8. Macroscopic observation of tablets and a kinetic analysis of release profiles suggested that, at pH 1.2, the drug was slowly released from the less-soluble CS/SBE-β-CyD complex formed on the surface of the tablet immediately after exposure to water, accompanied by the dissolution of the interpolymer complex and, ultimately, the erosion and disintegration of the tablet. In the case of the medium at pH 6.8, the formation of a gel by CS was the cause of the slow release, especially for CS/SBE-β-CyD tablets which were significantly gelated and both the diameter and thickness of the tablet had expanded. The in vitro slow releasing characteristic of the CS/SBE-β-CyD tablet was reflected in the in vivo absorption of the drug after oral administration to rats. These results suggest that a simple mixing of CS and SBE-β-CyD is potentially useful for the controlled release of a drug.
由壳聚糖(CS,分子量30 kDa)与磺丁基醚β-环糊精(SBE-β-CyD,取代度7)按1:1重量比形成的分子间复合物的溶解度低于任何一种原始组分。在pH 1.2的介质中,由CS和SBE-β-CyD简单混合物组成的片剂中法莫替丁的释放比在pH 6.8时更慢。片剂的宏观观察和释放曲线的动力学分析表明,在pH 1.2时,药物从片剂表面接触水后立即形成的低溶解度CS/SBE-β-CyD复合物中缓慢释放,伴随着聚合物间复合物的溶解,最终片剂发生侵蚀和崩解。在pH 6.8的介质中,CS形成凝胶是释放缓慢的原因,特别是对于CS/SBE-β-CyD片剂,其显著凝胶化,片剂的直径和厚度均增大。CS/SBE-β-CyD片剂的体外缓释特性反映在大鼠口服给药后药物的体内吸收上。这些结果表明,CS和SBE-β-CyD的简单混合对于药物的控释可能是有用的。