Date of Award


Document Type


Degree Name

Master of Science in Chemical Engineering (MSChE)


Chemical and Petroleum Engineering

First Advisor

Dr Ali H. Al-Marzouqi, PhD

Second Advisor

Prof. Alaa-Eldin Salem, PhD

Third Advisor

Prof. Amr Amin, PhD


Saffron (Crocus sativus. Linn) has attracted much attention over the last decade because it has a large number of potent and biologically active compounds such as crocin, crocetin, picrocrocin and safranal. Researchers have shown that safranal has high antioxidant and cytotoxicity activities against several types of tumour cells (e.g., hepatocellular carcinoma) both in-vitro and in-vivo. However, the low aqueous solubility of safranal prevents using it as a therapeutic or preventive agent.

β-cyclodextrin (β-CD) inclusion complexes are being used in pharmaceutical applications to alter physicochemical properties (e.g., solubility, volatility, stability, chemical reactivity, and bio-availability) of poorly water soluble drugs. Thus the aim of this work is to investigate the potential of different methods for the preparation of safranal-β-CD inclusion complexes in order to enhance the poor solubility and dissolution rate of safranal in aqueous solutions.

Inclusion complexes having a molar ratio of 1:2 (safranal-β-CD) were prepared using different methods such as kneading (KN), co-evaporation (COE), sealed-heating (SH), and supercritical CO2 (SC-CO2). Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD), scanning electron microscopy (SEM) and proton nuclear magnetic resonance spectroscopy (H-NMR) were used to identify the physicochemical properties of inclusion complexes. Phase solubility and dissolution measurements were also studied. Effects of temperature (35 and 55 °C) and pressure (100 and 300 bar) on the inclusion complexes prepared using the SC-CO2 method were also investigated.

The results indicated that the formation of safranal-β-CD inclusion complexes was affected by the preparation method being used, and the SC-CO2 method proved to be more effective than conventional techniques. FT-IR and H-NMR results indicated the formation of inclusion between β-CD and safranal in the complex prepared by different methods. A “Bs” type solubility with an apparent solubility constant (Ks) of 51.48 M-1 for safranal was obtained from the initial slope of phase solubility diagram. The intrinsic solubility of safranal was increased from 3.852 mM to 5.217 mM in the presence of 10.00 mM of β-CD. Therefore, the initial phase solubility of safranal was enhanced by about 35% in water solution. Dissolution rate studies showed that inclusion complexes might dissolve faster than pure safranal or even physical mixture of safranal-β-CD. Hence, β-CD could be useful for solid safranal formulations. The solvent-free product prepared by SC-CO2 showed high aqueous solubility and may provide minimal side effects for human use.