The size distribution of biodegradable polymer microspheres critically impacts the allowable routes of administration, biodistribution, and release rate of encapsulated compounds. We have developed a method for producing microspheres of precisely controlled and/or monodisperse size distributions. Our apparatus comprises spraying a polymer-containing solution through a nozzle with (i) acoustic excitation to produce uniform droplets, and (ii) an annular, non-solvent carrier stream allowing further control of the droplet size. We used this apparatus to fabricate poly(D,L-lactide-co-glycolide) (PLG) spheres. The acoustic excitation method, by itself, produced uniform microspheres as small as 30 μm in diameter in which ≥95% of the spheres were within 1.0-1.5 μm of the average. The carrier stream method alone allowed production of spheres as small as ∼1-2 μm in diameter from a 100-μm diameter nozzle, but generated broader size distributions. By combining the two devices, we fabricated very uniform spheres with average diameters from ∼5 to >500 μm. Furthermore, by discretely or continuously varying the experimental parameters, we fabricated microsphere populations with predefined size distributions. Finally, we demonstrate encapsulation and in vitro release of a model drug compound, rhodamine B. In summary, our apparatus provides unprecedented control of microsphere size and may allow development of advanced controlled-release delivery systems.

Original languageEnglish (US)
Pages (from-to)59-74
Number of pages16
JournalJournal of Controlled Release
Issue number1
StatePublished - May 18 2001


  • Controlled release
  • Drug delivery
  • Poly(lactide-co-glycolide)
  • Uniform microspheres

ASJC Scopus subject areas

  • Pharmaceutical Science


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