Department of Pharmaceutical Sciences, University of Padova, Via Marzolo, 5, 35131 Padova, Italy.
Acta Biomater. 2010 Jun;6(6):2246-53. doi: 10.1016/j.actbio.2009.12.021. Epub 2009 Dec 24.
Stability, defined as the reproducible behavior of a device upon its storage, is an important issue in pharmaceutical formulation. Silica xerogels obtained through the sol-gel route are relatively new as matrices for the controlled release of drugs. In some cases, it was observed that their behavior changes upon storage, so that they cannot always be defined as "stable". This occurs especially when gel processing is performed at mild temperatures, a procedure that may have to be used to prevent degradation of the embedded drug. This work investigated the use of inorganic catalysts as potential xerogel stability inducers when gel curing by heating is not applicable. Three compounds known to accelerate sol-gel polymerization, namely ammonia, sodium fluoride and sodium carbonate, were introduced during the polymerization of low-temperature processed inorganic and organically modified gels, and the effect of each compound on xerogel stability and drug release was monitored. The use of carbonate leads to formulations with good retention properties, as opposed to ammonia and NaF, which lead to poorly retentive xerogels in accordance with their known ability to increase porosity. Ammonia was shown to be a poor stability promoter independently of gel composition, as opposed to fluoride and carbonate, which both displayed stabilizing properties in a dose-dependent manner. No correlation was found between xerogel stability and drug release properties. An attempt was also made to correlate stability data with polymerization rates and wet gel syneresis time evolution with the purpose of identifying one or more synthesis parameters that could act as stability predictors for pre-formulation studies. No correlation was found between stability and syneresis data. A similar trend in the curve of gel time vs. catalyst concentration was observed for the two stabilizing catalysts, which was different for the non-stabilizing ammonia. It was concluded that the trend of this curve could potentially provide an indicator of catalyst stabilizing efficacy.
稳定性是指药物制剂在储存过程中可重复的行为，是药物制剂中的一个重要问题。通过溶胶-凝胶途径获得的硅胶干凝胶作为药物控制释放的基质相对较新。在某些情况下，观察到它们的行为在储存时发生变化，因此它们不能总是被定义为“稳定的”。这种情况尤其发生在凝胶处理在温和温度下进行时，为了防止嵌入药物的降解，可能需要进行这种处理。本工作研究了在不适用通过加热进行凝胶固化时使用无机催化剂作为潜在的干凝胶稳定性诱导剂。在低温处理的无机和有机改性凝胶的聚合过程中引入了三种已知可加速溶胶-凝胶聚合的化合物，即氨、氟化钠和碳酸钠，并监测了每种化合物对干凝胶稳定性和药物释放的影响。与氨和 NaF 相比，使用碳酸盐会导致制剂具有良好的保留性能，因为它们具有增加孔隙率的已知能力，从而导致保留性能差的干凝胶。氨被证明是一种独立于凝胶组成的不良稳定性促进剂，而氟化物和碳酸盐则以剂量依赖的方式表现出稳定特性。未发现干凝胶稳定性与药物释放性质之间存在相关性。还尝试将稳定性数据与聚合速率和湿凝胶相分离时间演变相关联，目的是确定一个或多个可作为预配方研究的稳定性预测因子的合成参数。未发现稳定性和相分离数据之间存在相关性。对于两种稳定化催化剂，观察到凝胶时间与催化剂浓度之间的曲线存在相似的趋势，而对于非稳定化的氨则不同。结论是，该曲线的趋势可能为催化剂稳定效果提供指示。
