Čes. slov. farm. 2014, 63(5):217-221 | DOI: 10.36290/csf.2014.041

Optimization of technological processes for the preparation of tablets with a low content of warfarin by direct compression

Jan Muselík, Aleš Franc^*, Jana Štarková, Zuzana Matějková

Veterinární a farmaceutická univerzita Brno, Farmaceutická fakulta, Ústav technologie léků, Brno

Warfarin is a drug with anarrow therapeutic index. It is commercially available in the form of tablets with immediate release from many generic manufacturers. Though attempts are being made to replace it with new drugs, in the U.S.A.it is still the antithrombotic agent of the first choice. In the past there were cases when after replacement of the original brand preparation with the generic one, the patient suffered from complications such as the loss of control of anticoagulation and increased frequency of patient's visits to the physician. One of the critical parameters of tablets containing an active substance with anarrow therapeutic index (NTI) is content uniformity, which must comply with the pharmacopoeial requirements as well as the strict criteria of regulatory authorities in the validation of the manufacture of the solid dosage form. Content uniformity is affected by anumber of factors such as density, particle shape and size distribution, electrostatic charge, and concentration of the individual components. Of the technological parameters, it is mainly the intensity and length of mixing, shape of the mixing vessel and the mixer, the size of the charge, or the degree of filling of the mixing device, etc. This paper deals with the influence of the mixing time and concentration of the drug on the content uniformity of warfarin-containing tablets. In mixing the mixtures of solid substances, where the active substance is included in alow concentration, there occurs the so-called mixing-out and segregation of the active substance. For this reason it is necessary to optimize the period of mixing. This study managed to optimize the mixing time of mixtures prepared with the use of the patented technology of the Veterinary and Pharmaceutical University Brno and further to prepare tablets with varying content of warfarin (2-10 mg) from acommon blend, which fulfil the pharmacopoeial requirements as well as the requirements of regulatory authorities for content uniformity.

Keywords: content uniformity; warfarin; blending time; narrow therapeutic index; common blend

Received: September 8, 2014; Accepted: September 16, 2014; Published: May 1, 2014  Show citation