RESEARCH ON ANTI-TB FDC PRODUCTS

Our lab has been the first one to solve decades old mystery of fall in bioavailability of rifampicin from anti-tuberculosis fixed-dose combination products. We established that this was due to interaction of rifampicin and isoniazid in stomach acid conditions. We investigated the mechanism of the reaction and found the formation of hydrazone upon reaction of rifampicin and isoniazid, which was isolated and even supplied as standard to companies and investigators around the globe. A limit of hydrazone has been set in latest monongraphs on anti-TB drugs in International Pharmacopoeia. Another impact of the work has been start of research on development of formulations, where reaction between rifampicin and isoniazid is duly hindered and formation of hydrazone is limited to pharmacopoeial limits.

Another set of studies focused on the presence of less active (R,S)-ethambutol dihydrochloride (EB2HCl) in bulk drug samples and anti-tuberculosis products. The unwanted isomer was found to be present in multiple API samples and marketed FDC products from 30-100%. A DSC test was devised for the purpose and this research lead to changes in monographs of Ethambutol hydrochloride in Indian and European Pharmacopoeias.

Nearly 40 papers were published on bioavailability, stability and quality issues of anti-TB drugs.

 STRESS TESTING AND ESTABLISHMENT OF STABILITY-INDICATING ASSAYS

Again our lab has been the first one to outline detailed guidelines on stress testing of drugs and also published critical aspects in the establishment of stability-indicating assays. The publications set the tone and were catalytic to initiation of research on these aspects in academia and industry all over the world.

STUDY OF DEGRADATION CHEMISTRY OF DRUGS USING SOPHISTICATED HYPHENATED TOOLS

The Eurpoean and WHO guidelines on stability testing of existing drugs and products allow submission of data (as a part of the dossier) on degradation chemistry and mechanisms of generic drugs, if the same are available in the scientific literature. To help the Indian and Global generic Industry, a program was initiated in our laboratory to publish studies on degradation chemistry of drugs using sophisticated hyphenated tools like LC-NMR and LC-MS. We have already worked upon almost 30 drugs and data on majority of them have been published in peer reviewed journals. In a few invited reviews, we have also proposed strategies for carrying out characterization of the degradation products, drug-drug/drug-excipient interaction products, which are now being followed globally.

CHARACTERIZATION OF DRUG METABOLITES

Our laboratory again ahs been the first in academia in India to start research on in vitro and in vivo metabolism of drugs. We have been able to establish very well in this field and our good output attracted collaboration from Bristol Myers Squibb, which is being implemented successfully in the institute.