硝苯地平-海藻酸钠缓释片的制备和性能研究

Preparation and properties of nifedipine-alginate sodium sustained release tablets

目的制备硝苯地平-海藻酸钠缓释片,考察海藻酸钠的含量对其抗张强度、体外释放性能和稳定性的影响。方法以直接压片法制备硝苯地平-海藻酸钠缓释片;在海藻酸钠含量为60、100、140mg的条件下,测定其厚度和抗张强度;建立硝苯地平的体外分析方法,测定硝苯地平-海藻酸钠缓释片在人工胃液(前2h)和人工肠液(后22h)中的释放曲线,考察片剂的稳定性,并探讨海藻酸钠含量对片剂释放性能和稳定性的影响。结果海藻酸钠含量为60、100、140mg片剂的抗张强度依次为2.86、2.71、2.67 MPa,无显著性差异。在胃液环境中释放2h后,3种片剂累积释放率依次为60.3%、46.7%、35.6%,随海藻酸钠含量升高而降低(P<0.05)。在肠液环境中释放10h后,3种片剂累积释放率依次为86.5%、74.6%和61.6%,随海藻酸钠含量升高而下降(P<0.05)。释放24h后3种片剂累积释放率达到98.3%、91.3%、85.6%,片剂3的释放率比片剂1和2降低(P<0.05)。片剂对高湿、高温环境稳定性强,但对光的稳定性弱。结论硝苯地平-海藻酸钠缓释片的厚度和抗张性能与海藻酸钠含量无关,海藻酸钠能够降低其在胃液中的突释效应,提高其在肠液环境中的缓释性能和对光的稳定性。

Objective To prepare nifedipine-alginate sodium sustained release tablets （NAlT）, and to evaluate the im pact of alginate sodium （A1） content on tensile strength, in vitro release properties and stability of NAlT. Methods NAITs were prepared by direct compression method. Tablet thickness and tensile strength with 60, 100 or 140 mg A1 were tested. In vitro assay was established, and the in vitro release profiles of NAITs at artificial gastric liquid （2 h before） and intestinal liquid （22 h after） were determined and the tablet stability was tested. The impact of A1 content on tablet release properties and tablet stability was discussed. Results The tablet thickness was 3.27, 3.21 or 3.18 mm with A1 of 60, 100 or 140 rag, and the tensile strength was 2.86, 2.71, or 2.67 MPa respectively, without significant difference. After 2 h release in the gastric environment, the cumulative releasing rate was 60. 3%, 46.7% and 35.6% for the 3 tablets, decreasing with the increase of A1 content （P〈0.05） . After 10 h release in the intestinal environ ment, the cumulative release rate of tablet was 86.5%, 74. 6% and 61.6%, decreasing sequentially （P〈0.05） . After 24 h release, with the increase of A1 content, the cumulative releasing rate was 98.3%, 91.3% and 85.6% for the 3 tablets, decreasing （P〈0.05） . The tablet stability was strong in high-humidity and high temperature environment, but weak under light. Conclusion The tablet thickness and tensile strength of NA1T are not related to A1 content. A1 can lower the initial burst release of NA1T in the gastric environment and improve NA1T sustained release property in the intestinal environment, and also strengthen the tablet stability under light.