Captisol®: an efficient carrier and solubilizing agent for essential oils and their components

Email: lamotte@univ littoral.fr ‐ Abstract Essential oils (EOs) and their individual components have several biological properties and are used in cosmetics, food and pharmaceutical industries. However, their application still presents a challenge owing mainly to their volatility and their poor aqueous solubility and stability. The aim of this study was to evaluate, for the first time, the ability of Captisol® (sulfobutylether‐ ‐ β cyclodextrin, SBE CD) and Captisol G® (sulfobutylether cyclodextrin, SBE CD) to encap‐ ‐ β ‐ ‐ ‐ γ ‐ ‐ γ sulate the main volatile components of six essential oils (EOs), to enhance the aqueous solubility of these EOs and to generate controlled release systems. The performance of these CDs was compared to hydroxypropyl cyclodextrin (HP CD) and cyclodextrin ( CD), respectively. ‐ ‐ β ‐ ‐ β γ‐ γ‐ Formation constants (K f ) of the 40 inclusion complexes were determined by Static Headspace‐ Gas Chromatography (SH GC). Then, Total Organic Carbon (TOC) was used to explore and quan‐

where A 0 and A CD stand for the peak areas of each EO component in the absence and the presence of CD, respectively; [CD] 0 is the initial concentration of CD.
K f values for the standard guests were determined using a SH GC titration method using different CD concentrations and a constant guest concentration as described previously. 15 All measurements were conducted using an Agilent headspace autosampler and a Perkin Elmer Autosystem XL equipped with a flame ionization detector using a DB624 column gas chromatography.
Temperature conditions were set as follows: initial temperature of 50°C for 2 min, increased to 190°C at 5°C/min giving a total runtime of 30 min. Nitrogen was used as carrier vector. Main volatile components in EOs were identified on the basis of GC retention times, determined by using EO standard components in the same conditions.

| Phase solubility studies
Phase solubility studies were carried out according to the method described by Higuchi and Connors (1965). 21

| Release studies
The release studies were performed using multiple headspace extrac- where A t and A 0 are the peak area of each EO component at time t and time 0.
The remaining percentages of free or encapsulated EO were also determined as follows: where A Σ t and A Σ 0 stand for the sum of peak areas of the entire EO at time t and time 0.
The GC settings were set as described in the section above.

| Statistical analysis
The solubility values of EOs in the presence of HP CD or Captisol® --β were compared using Student's t test. The significance level was set at Results are listed in Table 2.
It's worthy to note that the number of glucose units determines the cavity diameter of CDs ( Figure 1). Thus, HP CD and Captisol® --β present the same cavity diameter, narrower than that of Captisol G® and CD which in turn have identical cavity diameter. Moreover, no γ-K f values were previously reported for all the ten guests, neither with

Melaleuca alternifolia
Tea tree Terpinene 4 ol, terpineol, terpinene, terpinene, terpinolene, As we can obviously see in Table 2, K f values determined by both, the rapid and the titration, SH GC methods were consistent. Captisol® and HP CD showed better complexation ability than Captisol G® --β and CD towards all ten guests reflected by higher K γf values. This is due to the fact that the performance of CDs mainly depends on the geometric complementarity between their cavity and the guest. 23 Conversely, K f values revealed weaker binding potential of Captisol G® and CD for all guests. Only caryophyllene, a bicyclic γ-βsesquiterpene, is well recognized by Captisol G® and CD. This bulky γ-compound fits better into the cavity of CD and its derivatives than γlinear or monocyclic compounds. 26 For all aromas, Captisol® and HP CD showed better complexa---β tion ability than Captisol G® and CD with Captisol® being the most γefficient. These results indicated that Captisol® could be considered as an encouraging candidate to formulate aroma inclusion complexes for pharmaceutical applications.

| Phase solubility studies
The studied EOs are very complex mixtures and present a large variety of components (Table 1) Table 3.

At each CD concentration, values obtained for HP CD and --β
Captisol® were compared using statistical analysis. No significant differences were found for the two CDs ( < 0.05). Despite that p Captisol® showed higher binding affinity (higher K f values) than   Table 4 and illustrated for Mandarin EO, as an example, in Figure 5.
We could notice from Figure 5 and Table 4