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Slow Release Formulations of Inhaled Rifampin

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Abstract

Rifampin microspheres were prepared by spray drying using either polylactic acid (PLA) or poly(lactic-co-glycolic acid) (PLGA) polymers in different drug to polymer ratios (90:10 to 5:95, w/w). The in-vitro release characteristics, particle-size distribution, and cytotoxicity (in an alveolar macrophage cell line) and pharmacokinetics in rats after pulmonary instillation were evaluated. Increasing the polymer content from 10% to 95% slowed down the in vitro drug release with PLGA particles showing a steeper change with increasing polymer content (100% to 20% drug release over 6 h) than PLA particles (88% to 42% drug release over 6 h). PLA microsphere formulations revealed lack of cytotoxicity and a mass median aerodynamic diameter (MMDA) of 2.22–2.86 μm, while PLGA particles were larger (MMDA of 4.67–5.11 μm). Pharmacokinetics differed among the formulations with the 10% PLA formulation showing a distinct sustained release (t max of 2 h vs 0.5 h of free drug) and a systemic bioavailability similar to that of free drug. Formulations with high polymer content showed a lower relative bioavailability (30%). This suggested that an optimal release rate existed for which a distinct amount of drug was delivered over an extended period of time.

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Authors and Affiliations

  1. Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, 32610, USA

    Intira Coowanitwong, Vikram Arya & Günther Hochhaus

  2. Department of Industrial Pharmacy, College of Pharmacy, Chulalongkorn University, Bangkok, Thailand

    Poj Kulvanich

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  1. Intira Coowanitwong
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  2. Vikram Arya
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  3. Poj Kulvanich
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  4. Günther Hochhaus
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Correspondence to Günther Hochhaus.

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Coowanitwong, I., Arya, V., Kulvanich, P. et al. Slow Release Formulations of Inhaled Rifampin. AAPS J 10, 342–348 (2008). https://doi.org/10.1208/s12248-008-9044-5

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  • DOI: https://doi.org/10.1208/s12248-008-9044-5

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