Bhagavan H N, Wolkoff B I
Hoffmann-La Roche Inc., Division of Vitamins and Fine Chemicals, Nutley, New Jersey 07110.
Pharm Res. 1993 Feb;10(2):239-42. doi: 10.1023/a:1018938911420.
The goal of this study was to examine if the current USP disintegration standard for vitamin C tablets (max. 30 min in water at 37 degrees C with disks) is adequate or if a tighter disintegration standard (e.g., European compendia max. 15 min) should be recommended based on bioavailability considerations. Four formulations of 500-mg vitamin C tablets ranging in mean disintegration time from 9 to 120 min were compared with a standard vitamin C solution in a double-blind clinical trial with 15 subjects. The products were administered with a standard breakfast. The data show that a solution of vitamin C and a fast-disintegrating tablet (8-9 min) have equal but significantly lower bioavailability than tablets with longer disintegration times (30, 60, 120 min). Tablets with a mean disintegration time of 60 min showed the highest bioavailability. When the disintegration test was performed without disks, disintegration times increased so much that only the tablets with the fastest disintegration time (which were also the tablets with the lowest bioavailability) met the current USP disintegration time limit. Based on the results of the study, changes in the USP standard to omit the disks or to shorten the disintegration time will not achieve enhanced bioavailability but will result in reduced vitamin C absorption. In vitro dissolution of vitamin C tablets did not show the traditional relationship with bioavailability.
本研究的目的是检验美国药典（USP）目前对维生素C片的崩解标准（在37摄氏度水中使用片碟时最长30分钟）是否足够，或者基于生物利用度的考虑，是否应推荐更严格的崩解标准（例如，欧洲药典最长15分钟）。在一项针对15名受试者的双盲临床试验中，将平均崩解时间在9至120分钟之间的四种500毫克维生素C片制剂与标准维生素C溶液进行了比较。这些产品与标准早餐一起服用。数据显示，维生素C溶液和快速崩解片（8 - 9分钟）的生物利用度相等，但显著低于崩解时间较长（30、60、120分钟）的片剂。平均崩解时间为60分钟的片剂显示出最高的生物利用度。当在不使用片碟的情况下进行崩解试验时，崩解时间增加得如此之多，以至于只有崩解时间最快的片剂（也是生物利用度最低的片剂）符合目前USP的崩解时间限制。基于该研究结果，USP标准中省略片碟或缩短崩解时间的改变不会提高生物利用度，反而会导致维生素C吸收减少。维生素C片的体外溶出与生物利用度之间未显示出传统的关系。
