Shaheen Sharif M, Yamaura Kazuo
Faculty of Textile Science and Technology, Ueda City, Tokida 3-15-1, Nagano, Japan.
J Control Release. 2002 Jun 17;81(3):367-77. doi: 10.1016/s0168-3659(02)00085-8.
Theophylline (TH) was loaded in an a-PVA/NaCl/H2O hydrogels system by one cycle gelation only at -20 degrees C. However, it developed some unwanted crystal-like structure surrounding the hydrogels while kept at room temperature. The physical, chemical and thermal analyses of this crystal-like structure indicated TH embedded with thin hydrogels of a-PVA/NaCl. Later during dissolving of feed-mixture at least 3 h heat treatment with proper mixing at high temperature contributed hydrogels of almost no crystal-like structure. 3% of TH was successfully loaded by this way. This type of hydrogels showed Fickian type drug release (Higuchi Model) and it showed a more sustained effect than that of traditional cyclic FT. Comparatively lower release rate, diffusion coefficient and kinetic constant values of this system prevail over other systems studied here. A DSC thermogram revealed that apparently homogeneous microgel junctions might play the key role behind the above properties. Moreover the a-PVA/TH/NaCl/H2O system depresses the freezing point at -30 degrees C instead of above this temperature. The hydrogels of this system were also prepared by freezing at -30 degrees C for 16 h as one cycle. Three cycles were done in cyclic FT (freezing at -30 degrees C for 16 h and thawing at room temperature for 8 h). Drug release was studied for a total of 750 min. Up to the asymptotic value, 10.5 h TH release from the hydrogel matrices of the a-PVA/NaCl/H2O system (gelation at -20 degrees C) and 6.5 h from those of a-PVA/NaCl/H2O (freezing at -30 degrees C) and a-PVA/H2O systems (cyclic FT) were found.
仅在-20℃下通过一个循环凝胶化过程将茶碱（TH）负载到α-PVA/NaCl/H₂O水凝胶体系中。然而，当该体系在室温下保存时，水凝胶周围会形成一些不需要的晶体状结构。对这种晶体状结构进行的物理、化学和热分析表明，TH嵌入了α-PVA/NaCl的薄水凝胶中。后来在进料混合物溶解过程中，在高温下进行至少3小时的适当混合热处理，得到了几乎没有晶体状结构的水凝胶。通过这种方式成功负载了3%的TH。这种类型的水凝胶呈现菲克型药物释放（ Higuchi模型），并且与传统的循环冻融法相比，其缓释效果更好。该体系相对较低的释放速率、扩散系数和动力学常数优于本文研究的其他体系。差示扫描量热图显示，明显均匀的微凝胶连接可能是上述特性背后的关键因素。此外，α-PVA/TH/NaCl/H₂O体系在-30℃而不是高于该温度时降低了冰点。该体系的水凝胶也通过在-30℃下冷冻16小时作为一个循环来制备。在循环冻融法（在-30℃下冷冻16小时并在室温下解冻8小时）中进行了三个循环。总共研究了750分钟的药物释放。达到渐近值时，发现来自α-PVA/NaCl/H₂O体系（在-20℃凝胶化）水凝胶基质的TH释放时间为10.5小时，来自α-PVA/NaCl/H₂O（在-30℃冷冻）和α-PVA/H₂O体系（循环冻融法）的水凝胶基质的TH释放时间为6.5小时。
