Rifampicin raw materials complexities and approaches to address solubility and in vitro permeability

Abstract

Tuberculosis is classified as a global emergency because it is taking lives at an alarming rate and developing countries with insufficient health care systems are primarily affected. Fixed dose combination drugs (FDCs) were created to improve patient compliance and reduce the appearance of drug resistance, but unfortunately this drug combination has a few shortcomings, where rifampicin is a drug well-known for its problematic outcomes regarding bioavailability in FDCs. After a thorough literature study, it was found that rifampicin pose with different challenges like poor solubility and an amorphous content which could result in poor bioavailability. The poor solubility leads to issues or questions regarding the poor wettability of rifampicin. Surfactants are known to improve the wettability of poorly water soluble drugs. By making use of the surfactant sodium lauryl sulphate (SLS), the surface tension of rifampicin could be lowered and possibly result in an improvement of wettability of the drug. This could further lead to an increase in solubility of the drug and drug permeability, and consequently lead to better bioavailability. This hypothesis was tested by using dissolution studies and permeability studies with the Caco-2 model. Rifampicin powder in water and SLS showed enhanced solubility from the lowest concentration (0.05%) SLS in comparison with rifampicin powder in distilled water alone. Rifampicin powder in 0.20-0.30% SLS showed a significant increase in the solubility profile due to an increase in the wettability of the powder. For rifampicin in 0.1 M HCL the solubility was 2121.39 μg/ml after 360 min. In distilled water a solubility value of 872.05 μg/ml was obtained after 360 min, whereas in the presence of 0.30% SLS rifampicin solubility increased remarkably to 2344.88 μg/ml after 360 min. The 0.30% SLS resulted in the best dissolution profile, even better than the current pharmacopoeia medium, i.e. 0.1 M HCl (2121.39 μg/ml). With the Caco-2 model it was found that rifampicin in SLS can influence the paracellular permeability and can have an impact on intestinal absorption. SLS has a pronounced effect on tight junctions and the permeation of rifampicin was remarkably increased, but due to the cell toxicity of SLS the permeation studies should be tested on a more robust cell model. These studies showed that the poor solubility of rifampicin is a result of poor wettability and these issues need to be dealt with before any further steps are taken towards improving the bioavailability of the drug.