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.