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Lipid Nanocarrier-Mediated Drug Delivery System to Enhance the Oral Bioavailability of Rifabutin

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Abstract

Rifabutin (RFB) is prescribed for the treatment of tuberculosis infections as well as Mycobacterium avium complex (MAC) infection in immunocompromised individuals and HIV patients. With a view to develop a sustained release oral solid lipid nanoformulation (SLN), RFB was encapsulated in glyceryl monostearate (GMS) nanoparticles. The rifabutin solid lipid nanoparticles (RFB-SLNs), prepared by the solvent diffusion evaporation method, had a size of 345 ± 17.96 nm and PDI of 0.321 ± 0.09. The stability of RFB-SLNs was investigated in simulated gastric fluid (SGF) pH 2.0, simulated intestinal fluid (SIF) pH 6.8 and physiological buffer (PBS) pH 7.4. The gastric medium did not affect the SLNs and were found to be stable, while a sustained release was observed in SIF up to 48 h and in PBS up to 7 days. The pharmacokinetic profile of a single oral administration of RFB-SLNs in mice showed maintenance of therapeutic drug concentrations in plasma for 4 days and in the tissues (lungs, liver and spleen) for 7 days. Oral administration of free RFB showed clearance from plasma within 24 h. The relative bioavailability of RFB from SLNs was five fold higher as compared to administration with free RFB. The intent of using lipid nanocarriers is primarily to enhance the oral bioavailability of rifabutin and eventually decrease the dose and dosing frequency for successful management of MAC infection.

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Acknowledgments

This research was financially supported by a grant from the Indian Council of Medical Research (ICMR), New Delhi, India, with Senior Research Fellowship (SRF) to one of the authors (PN).

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Authors and Affiliations

  1. Lifecare Innovations Pvt Ltd, Laboratory for Translational Research in Nanomedicine, Biotech Park, Janakipuram, Lucknow, 226021, India

    Pradip Nirbhavane, Nalini Vemuri & Gopal Krishan Khuller

  2. Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab, 160062, India

    Neeraj Kumar

Authors
  1. Pradip Nirbhavane
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  2. Nalini Vemuri
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  3. Neeraj Kumar
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  4. Gopal Krishan Khuller
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Corresponding author

Correspondence to Nalini Vemuri.

Ethics declarations

All protocols were approved by the Institutional Animal Ethics Committee (IAEC) of National Institute of Pharmaceutical Education and Research (N.I.P.E.R.), Mohali, India and the experiments were performed in accordance with Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), India.

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The authors declare that they have no conflicts of interest.

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Nirbhavane, P., Vemuri, N., Kumar, N. et al. Lipid Nanocarrier-Mediated Drug Delivery System to Enhance the Oral Bioavailability of Rifabutin. AAPS PharmSciTech 18, 829–837 (2017). https://doi.org/10.1208/s12249-016-0559-2

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  • DOI: https://doi.org/10.1208/s12249-016-0559-2

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