目的 探讨基于不同直径的片剂的长径比(L/D Ratio)为参考的片剂几何特征对推拉式渗透泵(PPOP)药物传输系统的片剂特性(外观、硬度)以及药物释放的影响。方法 选择硝苯地平作为模型药物,并采用固定且相同的渗透泵片芯及包衣处方。选用3个直径的标准弧冲模(6、7、9 mm)压制双层渗透泵片芯,并考察片芯外观及硬度。在3个包衣增重水平(6%、12%、18%)对片芯进行包衣及激光打孔,并考察体外药物释放行为。结果 制备出了3种不同长径比的双层渗透泵片芯,分别是6 mm片芯(L/D,1.88)、7 mm片芯(L/D,1.18)和9 mm片芯(L/D,0.56)。在相同的压片压力下,高长径比片芯(例如,6 mm)的硬度显著升高。尤其在高压力条件下,高长径比片芯同时可能伴有更严重的飞边缺陷。经过包衣后,所有渗透泵片的释药模式遵循零级释放规律,但高长径比处方的释药速度更快。同时,由于飞边缺陷的存在,高长径比处方可能出现聚合物泄露并导致最终药物释放不完全。结论 本研究的结果揭示了片剂几何特性对推拉式渗透泵药物传输系统性能的影响,并提示其应在处方设计时加以关注考察。
Abstract
OBJECTIVE To explore the effect of tablet geometric characteristics, represented by tablet length to diameter ratio (L/D ratio) based on different tablet diameters, on tablet properties (hardness & appearance) and drug release behaviors of push-pull osmotic pump (PPOP) drug delivery system. METHODS Nifedipine was selected as the model drug, while the same formulations of tablet cores and coatings were adopted all through the study. Standard concave tablet tooling with three different diameters (6, 7 and 9mm) were used to compress bi-layer PPOP tablet cores and tablet hardness and appearance were checked accordingly. Those tablet cores were coated at three levels of weight gain (6%, 12% and 18%) followed by laser drill, and in vitro dissolution study were carried out to evaluate the drug release behaviors. RESULTS Three types of tablet cores with different geometric characteristics (6 mm L/D 1.88, 7 mm L/D 1.18 and, 9 mm L/D 0.56) were prepared. Higher L/D ratio of tablets (e.g. 6mm tablet) resulted in significantly higher tablet hardness under the same compression force. More severe crown defect was also observed for higher L/D ratio tablets, especially under high compression force. All drug release behaviors followed zero-order pattern, but higher L/D ratio led to a faster release rate. Meanwhile, due to the crown defects, the tablets with higher L/D ratio also tended to polymer dumping along the broken edge and resulting in incomplete drug release. CONCULUSION The results of this study implied that tablet geometric characteristics are very important and need to be carefully design in the PPOP product development.
关键词
推拉式渗透泵 /
聚氧化乙烯 /
硝苯地平 /
长径比
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Key words
push-pull osmotic pump /
polyethylene oxide /
nifedipine /
length-diameter ratio
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中图分类号：
R944
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参考文献
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