“Drugs stability testing is proving to be a serious challenge to the pharmaceutical industry. This is especially critical with reference to the anti tuberculosis drugs that are showing reduced bio-availability in composition,” stated Dr. Saranjit Singh representing NIPER, Chandigarh at the 57th IPC.

In his presentation at the ML Khorana Memorial Lecture on the second day of the first session at the 57th IPC at Hyderabad, Dr. Singh brought forth the serious issue of bio-availability problems which exist in fixed dose combinations. Referring to the reduction of bio-availability in Rifampicin, a commonly prescribed drug for TB control, he said that changes in physical composition occur during the tableting process. Hence the problem is due to solid state or a good manufacturing practice difficulty.

To provide a detailed analysis of the findings, the NIPER lab carried out extensive studies to ascertain the reasons for the reduction in bio-availability. A finding proved that the anti TB drug interference in the stomach is a leading cause for this.

“The drug mechanism interferes with the stomach and intestine acids. On an empty stomach there is heavy loss of decomposition,” Dr. Singh said.

Following the research findings, recommendations were made to coat the drug, add additives or segregate the doses instead of prescribing fixed dose combinations. This would allow tackle the issue of instability in fixed dose combinations, according to Dr. Singh.

The pilot study on fixed dose combinations conducted at NIPER has also provided evidence that presence of light disintegrated the physical appearance of the drug. "This will be a serious issue for drugs manufactured and stored under Tropical climate conditions," he explained.

Apart from environmental control standards maintained in drug production, Dr. Singh stated that barrier packaging should be adopted by companies to prevent the physical disintegration of the tablets or capsules. It is vital for pharmaceutical companies to highlight their labels and emphasise on the need to store drugs away from sunlight.

“A combination of factors has to be taken care of during the preparation and administration of fixed dose combinations to save the millions of TB patients. Factors like good science, innovation, networked efforts and more stringent regulatory controls could ensure quality of the formulations to prevent the instability and reduction in bioavailability in drugs,” averred Dr. Singh.

He concluded stating that while NIPER continued its efforts in studying the anti drug stability profile, it has also completed studies of anti TB drugs and its reactions in the combination of selected anti HIV drugs. In the wake of a growing HIV-TB population, the research is imperative.