摘要
目的制备新型压力依赖结肠定位释放胶囊剂(pressure dependant colon specific capsules,PD-CSC)。方法在低温条件下,利用整粒/粉碎机制备适宜大小脂肪酸甘油三酯(isocacao)颗粒,自制压力分析仪压制得温度敏感性囊芯物。乙基纤维素乙醇溶液(5%EC)包裹isocacao囊芯,包衣过程中随时用数显千分尺测定EC衣膜厚度,制得PD-CSC。流变仪测定PD-CSC基质在37℃熔化后的崩解压力,考察不同贮存条件下的衣膜稳定性。最后,通过恒河猴单剂量po含20mg咖啡因的PD-CSC,评价其药动学特征。结果PD-CSC的崩解具有压力依赖性,随着衣膜厚度的增加,崩解压力呈明显上升趋势。在不同贮存条件下和基质熔化后均未发现衣膜破裂现象。当2%枸椽酸三乙酯的乙基纤维素包衣膜厚度为(66±2)μm时,其体外崩解压力约为2N。药动学实验结果,咖啡因在体内达最高血药浓度时间(tmax)为(6.40±1.67)h,表明大部分药物在恒河猴结肠部位释放。结论本实验制备PD-CSC的崩解具有较好的压力依赖性,很好的体外稳定性和体内结肠定位释放特征。
Abstract
OBJECTIVE To prepare a novel intestinal pressure dependant colon specific capsules(PD-CSC).METHODS The appropriate granules of fatty acid triglyceride(Isocacao) were prepared by Quadro comil at low temperature.The capsule shaped core of Isocacao with temperature sensitive characteristics was obtained using self-made compact analyzer.The Isocacao cores were coated homogeneously with ethyl cellulose in ethanol solution(5% EC),and the thickness of EC layer were measured by micrometer during the process of coating till to get PD-CSC.The effect of EC thickness on the destructive force of PD-CSC was detected under rheometer after melted in 37 ℃.The stability of EC coating layer was investigated in different storage temperatures for one year.Finally,the pharmacokinetic studies were carried out after oral single dose administration of PD-CSC containing 20 mg of caffeine to rhesus monkeys.RESULTS The disintegration of PD-CSCs had a significant tendency of pressure dependant and the destructive force was increased with the thickness of EC membrane.The rupture of EC layer was not found while the products preserved in different conditions.The destructive force of PD-CSCs with the EC thickness around(66±2)μm and using 2% of triethyl citrate as plasticizer was close to 2 N.The results of pharmacokinetic study indicated that the time of maximum drug concentration(tmax) in the plasma was(6.40±1.67) h,obviously most of model drug released from PD-CSCs in the area of colon.CONCLUSION The disintegration of PD-CSCs prepared in the present test showed significant pressure dependant.And the products also displayed high stability in different condition and especially colon specific release characteristics.
关键词
压力 /
结肠定位释放 /
咖啡因 /
脂肪酸甘油三酯 /
乙基纤维素
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Key words
intestinal pressure /
colon specific release /
caffeine /
fatty acid triglyceride /
ethyl cellulose
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崔京浩;游本刚;唐丽华;村上正裕;高田宽治.
新型压力依赖结肠定位释放胶囊剂的制备与评价[J]. 中国药学杂志, 2008, 43(19): 1484-1487
CUI Jing-ho;YOU en-gng;TNG Li-hu;MURKMI Mshiro;TKD Knji.
Preparation and Evaluation of A Novel Intestinal Pressure Dependant Colon Specific Capsules [J]. Chinese Pharmaceutical Journal, 2008, 43(19): 1484-1487
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脚注
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基金
苏州大学引进人才基金(Q4132611)
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