rifampin and ethyl-acetate

The solvent evaporation method with premix membrane homogenization was applied, with class-3 ethyl acetate as organic solvent, to produce narrowly size-distributed rifampicin (RIF)-loaded poly(lactide-co-glycolide) (PLGA) microspheres for sustained lung delivery as aerosol. Microsphere formulations (simple or multiple emulsions, different PLGA and RIF concentrations) and process parameters (transmembrane pressure, SPG membrane pore diameter) were investigated as their effects on RIF content, microsphere size, aerodynamic properties of the freeze-dried powder and in vitro release profiles. Narrowly size distributed microspheres with diameters from 2 to 8 μm, satisfactory RIF contents (from 4.9 to 16.5%), 80% RIF release from 12h to 4 days, and adequate aerodynamic properties were prepared from a multiple emulsion and using SPG membrane pore diameter of 19.9 μm. The premix membrane homogenization appeared to be a rapid and efficient method to prepare monodisperse drug-loaded microspheres suitable for lung delivery as sustained-release microsphere aerosol.

Topics: Acetates; Aerosols; Antibiotics, Antitubercular; Delayed-Action Preparations; Drug Carriers; Drug Compounding; Drug Delivery Systems; Excipients; Lactic Acid; Lung; Membranes, Artificial; Microspheres; Models, Theoretical; Particle Size; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers; Rifampin; Solvents

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.

Topics: Acetates; Administration, Inhalation; Aerosols; Animals; Anti-Bacterial Agents; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Carriers; Drug Compounding; Emulsions; Kinetics; Lactic Acid; Membranes, Artificial; Microspheres; Oils; Particle Size; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Pressure; Rats; Rifampin; Solubility; Solvents; Technology, Pharmaceutical; Water