Oral Delivery of Ascorbic Acid Stabilized Rifampicin Nanoparticles for Enhanced Bioavailability of Rifampicin

Abstract

The present study followed two directional approaches to improve the disadvantage of rifampicin degradation that affects bio-availability of the drug. In the first approach ascorbic acid was used to stabilize rifampicin against degradation in the acidic environment and the second approach is to present rifampicin nanoparticles along with ascorbic acid. Ascorbic acid significantly reduced rifampicin degradation both in the presence and absence of isoniazid. Ascorbic acid and the nanoparticle approach together further influenced stability of rifampicin against degradation in the acidic environment. The stability of rifampicin from the above approaches was reflected in reduced degradation and increased release of rifampicin in the acidic environment. In-vivo study revealed improved pharmacokinetics of rifampicin from nanoparticles coupled with ascorbic acid. In conclusion, the results of the present study demonstrate that degradation of rifampicin in combination with isoniazid in fixed dose formulations can be controlled by using ascorbic acid as stabilizing agent in appropriate concentration. It has been established that tuberculous patients are recommended supplementation of ascorbic acid (1000mg/day) to improve the immune system against tuberculosis and therefore our study justifies the recommendation of ascorbic acid addition to rifampicin formulations in order to control degradation and improve bioavailability of rifampicin following oral ingestion for effective management of tuberculosis. Extrapolation of the findings of the present study to humans, may address the clinical implications of this approach. The results of the study clearly demonstrated the beneficial effects of ascorbic acid co-administration in improving bioavailability of rifampicin that can help control TB effectively. Further study is recommended for preclinical and clinical outcome and thus its viability in the design of fixed dose combination of rifampicin, isoniazid, pyrazinamide, ethambutol including ascorbic acid for better management of TB infection.