Compatibility Between Four Anti-TB Drugs and Tablet Excipients Determined By Microcalorimetry

Area of Science:

• Pharmaceutical Sciences
• Drug Stability
• Tuberculosis Therapeutics

Background:

• Tuberculosis (TB) treatment often involves fixed-dose combinations (FDCs) for improved patient adherence.
• Previous studies indicated no incompatibility between rifampicin, isoniazid, pyrazinamide, and ethambutol HCl at 40°C.
• Understanding drug-excipient interactions is crucial for TB FDC formulation stability.

Purpose of the Study:

• To assess potential incompatibilities of a four-drug TB FDC at an elevated temperature (50°C).
• To investigate interactions between the four TB drugs and common tablet excipients.
• To evaluate the stability of the combined drug formulation.

Main Methods:

• Isothermal microcalorimetry was employed to detect thermal events indicative of drug interactions.
• Studies were conducted at 50°C, with and without controlled humidity.
• Excipients were tested individually with each drug and then with the four-drug combination.

Main Results:

• No incompatibilities were observed between individual drugs and excipients.
• No incompatibilities were found between excipients themselves.
• Significant incompatibility was detected when the four drugs (rifampicin, isoniazid, pyrazinamide, ethambutol HCl) were combined.

Conclusions:

• The four-drug TB FDC formulation exhibits instability at 50°C due to drug-drug interactions.
• Excipients used in the formulation do not appear to cause incompatibilities with individual drugs.
• Further investigation into the specific drug-drug interactions within the FDC is warranted for formulation optimization.