Čes. slov. farm. 2012, 61(6):271-275

Evaluation of content uniformity of tablets with a low content of the active ingredient with a narrow therapeutic index

Jan Muselík^*, Aleš Franc

Ústav technologie léků VFU, Brno

A short time ago there was a discussion about the use of NTI drugs such as warfarin. In the treatment by generic drugs some medical complications and deaths due to occult bleeding were retrospectively monitored. As a result of these observations, the generic substitutions with tablets containing warfarin were banned in the U.S. as there was a belief that generics have different pharmacokinetics. But a subsequent research found that different plasma levels are not due to generic drugs, but they are caused by different individual responses of the organism and especially by not uniform contents of warfarin in individual tablets. The different contents are caused by the method of direct compression where there is no granulation of the tablet blend before compressing. The method of direct compression, however, is very convenient in terms of time, technological feasibility and cost of cure. This report seeks to map the problems of direct compression in the production of tablets containing warfarin, concrete examples showing the relationships between selected parameters and the content uniformity of dosage form. Specifically, it is the influence of the density fillers and addition of the lubricant in various stages of mixing. On the basis of the application of statistical criteria according to the requirements of the FDA for the manufacture of tablets and with the use of the specific parameters of raw materials, the study has demonstrated that the technology of direct compression containing warfarin results not only in safe pharmacotherapy, but it also saves time, materials and cost of manufactured drugs.

Keywords: content uniformity; warfarin; GMP; validation; narrow therapeutic index

Received: September 19, 2012; Accepted: October 8, 2012; Published: June 1, 2012  Show citation