Fabrication of PLG microspheres with precisely controlled and monodispersesize distributions

The size distribution of biodegradable polymer microspheres critically impa cts the allowable routes of administration, biodistribution, and release ra te of encapsulated compounds. We have developed a method for producing micr ospheres of precisely controlled and/or monodisperse size distributions. Ou r apparatus comprises spraying a polymer-containing solution through a nozz le with (i) acoustic excitation to produce uniform droplets, and (ii) an an nular, non-solvent carrier stream allowing further control of the droplet s ize. We used this apparatus to fabricate poly(D,L-lactide-co-glycolide) (PL G) spheres. The acoustic excitation method, by itself, produced uniform mic rospheres as small as 30 mum in diameter in which greater than or equal to 95% of the spheres were within 1.0-1.5 mum of the average. The carrier stre am method alone allowed production of spheres as small as similar to1-2 mum in diameter from a 100-mum diameter nozzle, but generated broader size dis tributions. By combining the two devices, we fabricated very uniform sphere s with average diameters from similar to5 to >500 mum. Furthermore, by disc retely or continuously varying the experimental parameters, we fabricated m icrosphere populations with predefined size distributions. Finally, we demo nstrate encapsulation and in vitro release of a model drug compound, rhodam ine B. In summary, our apparatus provides unprecedented control of microsph ere size and may allow development of advanced controlled-release delivery systems. (C) 2001 Published by Elsevier Science BN.