Precise control of PLG microsphere size provides enhanced control of drug release rate

Cory Berkland, Martin King, Amanda Cox, Kyekyoon Kim, Daniel W. Pack

Research output: Contribution to journalArticlepeer-review

340 Scopus citations


An important limitation in the development of biodegradable polymer microspheres for controlled-release drug delivery applications has been the difficulty of specifically designing systems exhibiting precisely controlled release rates. Because microparticle size is a primary determinant of drug release, we developed a methodology for controlling release kinetics employing monodisperse poly(D,L-lactide-co-glycolide) (PLG) microspheres. We fabricated 20-, 40- and 65-μm diameter rhodamine-containing microspheres and 10-, 50- and 100-μm diameter piroxicam-containing microspheres at various loadings from 1 to 20%. In vitro release kinetics were determined for each preparation. Drug release depended strongly on microsphere diameter with 10- and 20-μm particles exhibiting concave-downward release profiles while larger particles resulted in sigmoidal release profiles. Overall, the rate of release decreased and the duration increased with increasing microsphere size. Release kinetics from mixtures of uniform microspheres corresponded to mass-weighted averages of the individual microsphere release kinetics. Appropriate mixtures of uniform microspheres were identified that provided constant (zero-order) release of rhodamine and piroxicam for 8 and 14 days, respectively. Mixing of uniform microspheres, as well as control of microsphere size distribution, may provide an improved methodology to tailor small-molecule drug-release kinetics from simple, biodegradable-polymer microparticles.

Original languageEnglish
Pages (from-to)137-147
Number of pages11
JournalJournal of Controlled Release
Issue number1
StatePublished - Jul 18 2002


  • Controlled release
  • Piroxicam
  • Poly(lactide-co-glycolide)
  • Uniform microspheres
  • Zero-order release

ASJC Scopus subject areas

  • Pharmaceutical Science


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