Fabrication of PLG microspheres with precisely controlled and monodisperse size distributions

• Published in: Journal of controlled release 2001-05, Vol.73 (1), p.59-74
• Main Authors: Berkland, Cory, Kim, Kyekyoon (Kevin), Pack, Daniel W
• Format: Article
• Language: English
• Subjects: Algorithms; Biological and medical sciences; Controlled release; Drug Carriers - chemistry; Drug Compounding; Drug delivery; General pharmacology; Lactic Acid - chemistry; Medical sciences; Microscopy, Electron; Microspheres; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Poly(lactide-co-glycolide); Polyglycolic Acid - chemistry; polylactide-co-glycolide; Polymers - chemistry; rhodamine B; Rhodamines - chemistry; Ultrasonics; Uniform microspheres
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/S0168-3659(01)00289-9

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.