目的: 分析研究雷贝拉唑钠肠溶片在含乙醇溶液中释放机制,评估发生剂量倾泻的风险,并对市售制剂与参比制剂溶出曲线进行相似性比较。方法: 溶出条件为桨法,转速为100 r · min-1,溶出时间为120 min,利用高效液相色谱法（HPLC）测定不同浓度乙醇溶出介质下的7种市售制剂的溶出曲线,研究其释放机制并通过相似因子（f2）评价市售制剂与参比制剂Pariet®的相似度以及乙醇诱导的剂量倾泻风险。结果: 各市售制剂在5%乙醇浓度的0.1 mol · L-1盐酸介质中均有较好的乙醇耐受性;在20%乙醇浓度的0.1 mol · L-1盐酸介质中除D、E 2个厂家外,其他各市售制剂均有较好的乙醇耐受性;在40%乙醇浓度的0.1 mol · L-1盐酸介质中仅F厂家制剂有较好的乙醇耐受性,其他市售制剂均存在剂量倾泻风险。在含4种不同浓度乙醇的pH 8.0 Tris缓冲液中,各市售仿制制剂溶出行为与参比制剂均存在差异。结论: 在服用雷贝拉唑钠肠溶片期间,应禁止饮用白酒等高浓度酒精饮品,避免未知的安全风险。
Objective: To analyze and evaluate the mechanism of drug release for rabeprazole sodium enteric-coated tablets in ethanolic media and conduct the risk assessment for the dose dumping. The similarity of dissolution curves were compared between reference preparation and generic products. Methods: The dissolution conditions were the paddle method, the speed was 100 r · min-1, the dissolution time was 120 min. Release profiles of rabeprazole sodium enteric-coated tablets from 7 manufacturers in different ethanolic media were determined by HPLC. The release mechanism was studied and the similarity between the commercially available generic preparation and the commercially available reference preparation Pariet® was evaluated. The risk of dose dumping was evaluated by the similarity factor ( f2) of the release data. Results: All preparations showed good tolerance to ethanol in the 0.1 mol · L-1 hydrochloric acid with an alcohol concentration of 5%. All preparations showed good tolerance to ethanol in the 0.1 mol · L-1 hydrochloric acid with an alcohol concentration of 20%, except for D and E manufacturers. All preparations carried the risk of dose dumping in the 0.1 mol · L-1 hydrochloric acid with an alcohol concentration of 40% except F manufacturer. The dissolution behavior of each commercially available generic formulation differs from that of the reference formulation in pH 8.0 Tris buffer with 4 different concentrations of ethanol. Conclusion: In the course of clinical application of this drug, it is necessary to suggest that drinking high-concentration alcoholic beverages such as liquor should be prohibited to avoid the unknown security risks.
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