期刊
PHARMACEUTICAL RESEARCH
卷 17, 期 8, 页码 955-961出版社
KLUWER ACADEMIC/PLENUM PUBL
DOI: 10.1023/A:1007527204887
关键词
tuberculosis; rifampicin; PLGA; biodegradable microspheres; aerosols; controlled release
资金
- NHLBI NIH HHS [HL55789] Funding Source: Medline
Purpose. Particles with aerodynamic diameters of 1-5 mu m deposit in the periphery of the lungs and are phagocytized by alveolar macrophages, the primary site of Mycobacterium tuberculosis infection. Aerosols of biodegradable polymeric microspheres containing antitubercular agents may be delivered to the lungs to improve the treatment of tuberculosis. Methods. Poly(lactide-co-glycolide) (PLGA) microspheres containing rifampicin were prepared using solvent evaporation and spray drying methods. The solvent evaporation process was optimized using factorial experimental design and surface response methodology. The morphology, particle size, drug loading, and dissolution of microspheres was evaluated. Results. The spray dried rifampicin loaded PLGA microparticles were shriveled, unlike the spherical particles produced by solvent evaporation. Drug loadings of 20% and 30% were achieved for solvent evaporation and spray dried products, respectively. The particles prepared by solvent evaporation and spray drying had 3.45 mu m and 2.76 mu m median diameters by volume, respectively. Conclusions. Respirable rifampicin loaded PLGA microspheres were produced by both solvent evaporation and spray drying methods. These particles are being evaluated in an animal model of tuberculosis.
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