Preparation of rifampicin-loaded PLGA microspheres for lung delivery as aerosol by premix membrane homogenization.
The water-in-oil solvent evaporation method with premix membrane homogenization was investigated to improve productivity of the preparation of narrowly size-distributed poly(lactide-co-glycolide) (PLGA) microspheres for rifampicin lung delivery as dry aerosols. Using ethyl acetate as organic solvent, a coarse oil-in-water emulsion (or premix) was prepared under magnetic stirring and homogenized by extrusion through a Shirasu porous glass (SPG) membrane (5.9 microm porosity). Microspheres were obtained after dilution and solvent evaporation. Formulation parameters investigated were: PLGA concentration, transmembrane pressure and oil:water volume ratio. The optimal formulation parameters were then applied to prepare rifampicin-loaded microspheres. Loaded microspheres were 1.72+/-0.16 microm in diameter with a span of 0.86+/-0.04 and a rifampicin content of 52+/-6 microg/mg microspheres. Release studies in phosphate-buffered saline showed a linear release profile with 40% rifampicin release over 4.5 days. The MMAD of 2.63 microm of freeze-dried microspheres should be suitable for aerosol administration and delivery into the rat lungs by intratracheal insufflation.
Doan
T V P
TV
INSERM, ERI-23, 40 avenue du Recteur Pineau, 86000 Poitiers, France.
Olivier
J C
JC
D000085:Acetates / Q000737:chemistry; D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004339:Drug Compounding; D004655:Emulsions; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D008567:Membranes, Artificial; D008863:Microspheres; D009821:Oils / Q000737:chemistry; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011312:Pressure; D051381:Rats; D012293:Rifampin / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D014867:Water / Q000737:chemistry
D000085:Acetates; D000336:Aerosols; D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004655:Emulsions; D008567:Membranes, Artificial; D009821:Oils; D012997:Solvents; D014867:Water; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C007650:ethyl acetate; D012293:Rifampin