Plasticization and spraying of poly (DL‐lactic acid) using supercritical carbon dioxide: control of particle size

• Published in: Journal of pharmaceutical sciences 2004-04, Vol.93 (4), p.1083-1090
• Main Authors: Hao, Jianyuan, Whitaker, Martin J., Wong, Ben, Serhatkulu, Gulay, Shakesheff, Kevin M., Howdle, Steven M.
• Format: Article
• Language: English
• Subjects: Air Pressure; backpressure; Biological and medical sciences; Carbon Dioxide - chemistry; Chromatography, Supercritical Fluid; Cold Temperature; Delayed-Action Preparations; Drug Compounding; General pharmacology; Lactic Acid - chemistry; Medical sciences; Microscopy, Electron, Scanning; Particle Size; particles; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; plasticization; Plasticizers; poly (DL‐lactide); Polyesters; Polymers - chemistry; Rheology; supercritical CO2
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.20002

Exposure of poly(DL‐lactic acid) (PDLLA), and related polymers, to supercritical CO2 (scCO2) at or below, physiological temperatures leads to very effective plasticization and liquefying of the polymers. The phenomenon arises from the high solubility and interaction of the scCO2 in the polymer. Under these unique conditions, temperature and solvent labile molecules can be mixed efficiently into the liquefied polymer. This liquefied polymer/drug/CO2 mixture can then be sprayed into a collecting chamber, and during this process particles of drug‐loaded polymer are formed. This process is very different from rapid expansion and antisolvent based techniques that have been previously reported. In this article, we describe a method of controlling particle size during the spray process by introducing a backpressure of N2 in the collecting chamber. This backpressure dynamically regulates the loss of CO2 from the issuing polymer/CO2 mixture, leading to control over sprayed particle size. In situ observation of the viscosity of the plasticized polymer indicates that a backpressure of 68bar or greater is necessary to ensure the production of fine particles. The influences of backpressure and saturation temperature on particle size for the sprayed products are discussed in terms of observed PDLLA/CO2 mixture viscosities.