Respirable PLGA microspheres containing rifampicin for the treatment of tuberculosis: manufacture and characterization.
OBJECTIVE
Particles with aerodynamic diameters of 1-5 microm 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 microm and 2.76 microm 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.
O'Hara
P
P
Department of Biomedical Engineering, University of North Carolina at Chapel Hill 27599, USA. pohara@magellanlabs.com
Hickey
A J
AJ
D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000627:therapeutic use*; D002021:Buffers; D003890:Desiccation; D004337:Drug Carriers; D019344:Lactic Acid; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D012293:Rifampin / Q000008:administration & dosage / Q000627:therapeutic use*; D012997:Solvents; D013499:Surface Properties
D000904:Antibiotics, Antitubercular; D002021:Buffers; D004337:Drug Carriers; D011108:Polymers; D012997:Solvents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D012293:Rifampin