Choi H, Lee M, Kim M, Kim C
College of Pharmacy, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Ku, Seoul, South Korea.
Int J Pharm. 1999 Nov 10;190(1):13-9. doi: 10.1016/s0378-5173(99)00225-2.
To investigate the effects of additives on the physicochemical properties of in situ gelling and mucoadhesive liquid suppository base, gelation temperature, gel strength and bioadhesive force of liquid suppository base, poloxamer 407 (P 407) and poloxamer 188 (P 188) (15/15%) were evaluated in the presence of following additives: solvent (ethanol, propylene glycol, glycerin), ionic strength-controlling agent (sodium chloride) and pH-controlling agent (hydrochloric acid, sodium monohydrogen phosphate, sodium dihydrogen phosphate). Among the additives studied, sodium chloride, sodium monohydrogen phosphate and sodium dihydrogen phosphate increased to a great extent the gel strength and the bioadhesive force of P 407/P 188 (15/15%) with a decrease in gelation temperature. Glycerin slightly decreased the gelation temperature and slightly increased the gel strength and bioadhesive force. However, the addition of 1% of sodium chloride, sodium monohydrogen phosphate or sodium dihydrogen phosphate caused a greater than 60-fold increase in gel strength and over a tenfold increase in bioadhesive force with 2-4 degrees C decrease of gelation temperature within optimal range, compared with P 407/P 188 (15/15%) alone. On the other hand, ethanol, propylene glycol and hydrochloric acid increased the gelation temperature and slightly decreased the gel strength and the bioadhesive force. Taken together, these findings indicate that the effect of additives on the physicochemical properties of liquid suppository bases depends on their bonding capacities, in that additives such as sodium chloride, sodium monohydrogen phosphate and sodium dihydrogen phosphate having strong cross-linking bonds with the components of liquid suppository base increase the strength and bioadhesive force of a gel compared to liquid suppository base alone, while additives such as ethanol, propylene glycol and hydrochloric acid having weaker hydrogen bonding result in a weaker response. Thus, sodium chloride and sodium phosphates appear to be promising additives for in situ gelling and mucoadhesive liquid suppository base, if used in adequate amounts.
为研究添加剂对原位凝胶化及黏膜黏附性液体栓剂基质理化性质、凝胶化温度、凝胶强度和液体栓剂基质生物黏附力的影响，在以下添加剂存在的情况下评估了泊洛沙姆407（P 407）和泊洛沙姆188（P 188）（15/15%）：溶剂（乙醇、丙二醇、甘油）、离子强度调节剂（氯化钠）和pH调节剂（盐酸、磷酸氢二钠、磷酸二氢钠）。在所研究的添加剂中，氯化钠、磷酸氢二钠和磷酸二氢钠在很大程度上提高了P 407/P 188（15/15%）的凝胶强度和生物黏附力，同时凝胶化温度降低。甘油使凝胶化温度略有降低，凝胶强度和生物黏附力略有增加。然而，与单独的P 407/P 188（15/15%）相比，添加1%的氯化钠、磷酸氢二钠或磷酸二氢钠会使凝胶强度增加超过60倍，生物黏附力增加超过10倍，且在最佳范围内凝胶化温度降低2 - 4摄氏度。另一方面，乙醇、丙二醇和盐酸提高了凝胶化温度，并略微降低了凝胶强度和生物黏附力。综上所述，这些发现表明添加剂对液体栓剂基质理化性质的影响取决于它们的结合能力，即与液体栓剂基质成分具有强交联键的添加剂如氯化钠、磷酸氢二钠和磷酸二氢钠，相比于单独的液体栓剂基质，会增加凝胶的强度和生物黏附力，而具有较弱氢键的添加剂如乙醇、丙二醇和盐酸则导致较弱的响应。因此，如果使用适量，氯化钠和磷酸盐似乎是原位凝胶化及黏膜黏附性液体栓剂基质有前景的添加剂。
