软胶囊崩解迟缓现象影响因素研究

Studies on the Cause of Retarded Dissolution of Soft Capsule Shell

目的 :研究储存条件以及软胶囊处方对明胶胶片稳定性的影响 ,探讨软胶囊崩解迟缓的原因。方法 :制备明胶胶片模拟软胶囊囊壳 ,采用溶胀动力学法测定明胶胶片平衡溶胀量 (Seq) ,同时测定软胶囊内容物溶媒PEG4 0 0中甲醛含量。以上述结果为指标 ,考察不同储存条件与胶囊处方对明胶胶片交联程度的影响。结果 :空白明胶胶片在 4 0℃条件下Seq与对照组具有极显著性差异 ,PEG4 0 0中甲醛含量增加。含有甘油、山梨醇、二氧化钛等辅料的胶片浸泡在PEG4 0 0中后Seq与对照组具有极显著性差异 ,PEG4 0 0中甲醛含量显著增加。加速条件下含有抗氧剂的胶片Seq与PEG4 0 0中甲醛含量变化不大。结论 :在考察的储存条件中 ,温度对软胶囊稳定性影响较大。含有一些常用辅料的明胶胶片易受PEG4 0 0中外源性醛类杂质的影响 ,Seq降低。低温保存、纯化辅料以及添加抗氧剂有助于缓解软胶囊崩解迟缓现象的发生。

AIM:To study the factors affecting the stability of soft capsule shell with swelling method and to discuss the cause of retarded dissolution. METHOD:The crosslink of differently formulated gelatin flakes,which simulate the soft capsule shell, was studied under different storing conditions, using the swelling parameter( S_ eq ) and the formaldehyde content in PEG400 as index. RESULT:Among all the storing conditions, the crosslinking extent reached the maxim level at higher storing temperature. Some additives such as the glycerin and titanium oxide make formulated flakes accessible to aldehyde in PEG400, thus its crosslinking increased; while flakes formulated with antioxidant and those without additives were less affected. CONCLUTION:Soft capsule retarded dissolution was mainly caused by gelatin's self-oxidation crosslinking and the aldehyde's crosslinking effect in additives. Purifying the additives, lowering storing temperature, adding antioxidants and using simple formulation can improve it.