Insulin and Insulin–Tripalmitin Particles Produced by a Supercritical Assisted Drying Process

Abstract

A supercritical assisted drying (SAD) process was employed to produce insulin submicroparticles from an ethanol/water solution. The effect of the processing conditions on the morphology, size, and thermodynamic activity of the produced particles was investigated. Insulin particles generated from the process were generally spherical with average sizes between 0.4 and 1.1 µm. FTIR, HPLC, the Lowry method, and DTA–TG were implemented to investigate the thermodynamic activity and solvent residue of the produced particles. Results showed that the ethanol content of the aqueous solution had a more sensitive effect on the thermodynamic activity of the insulin particles than other operating factors; a high content of ethanol tended to denature the insulin particles. A rapid expansion of supercritical solutions (RESS)–SAD combined process was proposed to produce insulin–tripalmitin composite particles. Results indicated that irregular composite particles with insulin content of 33.1%, having a bimodal particle size distribution with two peaks at 3.5 and 11.0 µm, were obtained at 50.0°C and 12.0 MPa. These particles revealed no initial burst with a sustained release of insulin of more than 400 min.

Keywords:

• Carbon dioxide
• Insulin particles
• Insulin-tripalmitin composites
• RESS
• Supercritical drying

ACKNOWLEDGMENTS

For financial support, the authors are grateful to NSFC (No. 21276212) and SRFDP (No. 20100121110009). The authors thank Prof. E.G. de Azevedo for use of the SigmaScan Pro software.

Notes

Note.

^a T = 45°C, p = 8.0 MPa, pH = 3, CO₂ flow rate = 13.7 NL/min, nozzle size = 100 µm.

Note:

^a The studied insulin samples can be found in these figures.

^b Thermodynamic activity determined by the Lowry method.

^c Determined by HPLC.