Raman spectroscopy as a complementary tool to assess the content uniformity of dosage units in break-scored warfarin tablets

- A Raman procedure has been developed to quantify the warfarin concentration in the potential fragments of scored tablets.
- Warfarin variability among portions of scored tablets was found to be around 5%.
- Repeatability and intermediate precision were found to be around 3%.

Due to the side effects of overdosing, the therapeutic dose of warfarin preparations must be very strictly controlled. In order to make it easier for the patient to take the required dose, two different strategies can be followed: The medicine can be commercialized in different dosages and/or tablets can be scored in order to make them easy to split. The splitting of the tablets introduces the question of how to control that the fractions contain the desirable amount of warfarin. The regulations regarding the content uniformity of dosage unit for scored tablets have changed considerably in the last 10 years, and they are still evolving. Warfarin is commercialized under the trademark of Aldocumar in four different preparations, containing 1, 3, 5 and 10 mg sodium warfarin per tablet. All these tablets are also scored, thus suggesting the possibility of splitting. A quantitative Raman method has been developed for the determination of warfarin in tablets and in the potential fragments, taking into account the score lines on the tablet surface. This method is suggested as an auxiliary procedure to verify the uniformity of API distribution in dividable tablets. A combination of a second derivative and standard normal variate (SNV) was used as spectral pre-treatments, and partial least squares (PLS) as the regression algorithm. The relative standard deviation in API content among portions was found to be less than 5%. An HPLC procedure has been used as a reference analytical method.

108