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Eucalyptol is the natural cyclic ether which constitutes the bulk of terpenoids found in essential oils of Eucalyptus spp. and is used in aromatherapy for treatment of migraine, sinusitis, asthma and stress. It acts by inhibiting arachidonic acid metabolism and cytokine production. Chemical instability and volatility of eucalyptol restrict its therapeutic application and necessitate the need to develop an appropriate delivery system to achieve extended release and enhance its bioactivity. However, the synthesis method of the delivery system must be suitable to prevent loss or inactivation of the drug during processing. In this study, supercritical carbon dioxide (scCO 2 ) was explored as an alternative solvent for encapsulation and co-precipitation of eucalyptol with polyethylene glycol (PEG) and/or polycaprolactone (PCL) using the particles from gas-saturated solution (PGSS) process. Polymers and eucalyptol were pre-mixed and then processed in a PGSS autoclave at 45 °C and 80 bar for 1 h. The mixture in scCO 2 was micronized and characterized. The presence of eucalyptol in the precipitated particles was confirmed by infrared spectroscopy, gas chromatography and mass spectrometry. The weight ratios of PEG-PCL blends significantly influenced loading capacity and encapsulation efficiency with 77% of eucalyptol encapsulated in a 4 : 1 composite blend of PEG-PCL. The particle size distribution of the PGSS-micronized particles ranged from 30 to 260 μm. ScCO 2 assisted microencapsulation in PEG and PCL reduced loss of the volatile drug during a two-hour vaporization study and addition of PCL extended the mean release time in simulated physiological fluids. Free radical scavenging and lipoxygenase inhibitory activities of eucalyptol formulated in the PGSS-micronized particles was sustained. Findings from this study showed that the scCO 2 -assisted micronization can be used for encapsulation of volatile drugs in polymeric microparticles without affecting bioactivity of the drug.

Microencapsulation of eucalyptol in polyethylene glycol and polycaprolactone using particles from gas-saturated solutions