Screening of bulk drug samples and anti-tuberculosis products for the presence of therapeutically less active diasteriomeric (R,S) form of ethambutol dihydrochloride.

BACKGROUND: The present study was carried out to screen various ethambutol dihydrochloride (EB2HCI) bulk drug samples and anti-tuberculosis (anti-TB) products for the presence of less active (R,S)-EB2HCl. METHODOLOGY: Samples of pure EB2HCl were received gratis from various companies and the formulations were procured from local market, and also from a Directly Observed Treatment Short-course (DOTS) centre. Some products available in the institute from Global Drug Facility were also included in the study. In total, 5 API samples and 35 formulations containing EB2HCI were investigated. These were subjected to evaluation for the presence of (R,S)-EB2HCl using a previously published differential scanning calorimetric method. The thermograms were recorded between 25 degrees C and 250 degrees C at a rate of 10 degrees C/min. RESULTS: 1 API sample and 12 formulations were found to contain (R,S)-EB2HCI up to an extent of 30-100%. One of the DOTS centres supply was also found to contain approximately 97% of the less active isomer. CONCLUSION: The presence of therapeutically inactive form of the EB2HCl from 30-100% in approximately 30% of the products in the local market is an alarming finding, which means low quality anti-TB products are in circulation. The same may be contributory to the developing resistance of the drugs against the mycobacterium.

Quality problems of anti-tuberculosis Fixed-dose Combinations (FDCS) A way forward.

Fixed dose combinations (FDCs) of anti-tuberculosis drugs (Rifampicin, Isoniazid, Pyrazinamide and Ethambutol hydrochloride) have several advantages over loose combinations of these drugs. Hence, the use of FDCs in the short course chemotherapy of tuberculosis is being promoted internationally. However, these products are associated with quality problems such as loss of bio-availability of Rifampicin and instability of the drugs in the combination. Recent research in Indian laboratories has helped in identification of the major reasons behind these problems, which suggest that an entirely different approach is required to that currently being recommended by the world bodies. The purpose of this article is to briefly discuss the twin quality problems and to highlight the potential forward ways.