Efficient Improvement of Eugenol Water Solubility by Spray Drying Encapsulation in Soluplus® and Lutrol F 127
Abstract
Herein, we present an elegant and simple method for significant improvement of eugenol water solubility using the polymers Soluplus® and Lutrol F 127 as carriers and spray drying as an encapsulation method. The formulations were optimized by adding myo-inositol—a sweetening agent—and Aerosil® 200 (colloidal, fumed silica)—an anticaking agent. The highest encapsulation efficiency of 97.9–98.2% was found for the samples containing 5% eugenol with respect to the mass of Soluplus®. The encapsulation efficiencies of the spray-dried samples with 15% eugenol are around 90%. Although lowering the yield, the addition of Lutrol F 127 results in a more regular particle shape and enhanced powder flowability. The presence of Aerosil® 200 and myo-inositol also improves the rheological powder properties. The obtained formulations can be used in various dosage forms like powders, granules, capsules, creams, and gels.
Introduction
Eugenol is a natural liquid compound with a spicy flavor and pleasant strongly aromatic scent. Its name originates from the old name of clove Eugenia caryophyllata (Syzygium aromaticum is the current one), since eugenol represents around 89% of the clove oil [1]. Other aromatic plants such as cinnamon, nutmeg, and basil also contain eugenol. Eugenol not only finds application in the food industry, cosmetics, and as a pesticide in agriculture, but also due to its antioxidant, antifungal, antibacterial properties, and even analgetic effect [2,3,4,5,6,7,8,9,10,11,12,13] is beneficial for pharmaceutical use. Eugenol and its derivates show in vitro activity against Mycobacterium tuberculosis and non-tuberculous mycobacteria [14]. For more than 90 years, in combination with ZnO, it has been used in dental medicine as a root canal sealer (endodontic sealer) [15,16]. However, eugenol is practically insoluble in water (less than 1 mg/mL at 20 °C) [17], which limits its bioavailability. An elegant way to improve its water solubility is by encapsulation in a water-soluble substance(s). Polymers such as Soluplus® and Lutrol F 127 are very suitable candidates for this purpose, since they are water-soluble and are approved for pharmaceutical use. Furthermore, Soluplus® is developed by BASF with the purpose to act as a matrix polymer for solid solutions and due to its amphiphilic chemical nature is capable of solubilizing poorly soluble drugs in aqueous media [18,19,20,21,22,23]. Lutrol F 127, also created by BASF, is a kind of poloxamer—a copolymer of ethylene and propylene oxides. Since it has an influence on the viscosity, it can be applied as a stabilizer for topically administrated suspensions and finds application in toothpastes and mouthwashes [24]. Its excellent solubilizing properties are useful for active substances with low solubility and it could also be applied to essential oils [24].
Spray drying is a widely used technique, which allows dry powders to be obtained from liquid solutions in one step [25,26,27,28]. It is used in the chemical, food, and pharmaceutical industries [29]. The speed of the process and the short drying time allow drying without degradation of even temperature-sensitive substances [30,31]. Several studies report the encapsulation of drugs and substances with therapeutic potential in Soluplus® by spray drying [18,32,33,34], but so far there is a lack of data in the literature on loading eugenol in Soluplus® and Lutrol F 127 using spray drying or other methods.
Peng et al. improved eugenol solubility by nanoliposome encapsulation using ethanol injection and dynamic high-pressure microfluidization [35]. The encapsulation efficiency was 59.2 ± 4.7%. Enhancement of the solubility of eugenol was also achieved by β-cyclodextrin inclusion complexes [36,37,38]. Talón and co-authors encapsulated eugenol by spray drying using soy lecithin and whey protein for the purpose of preparing antioxidant and antimicrobial powders for food applications [39]. They also studied how the addition of maltodextrin, oleic acid, and chitosan would influence the encapsulation efficiency, thermal stability, and release kinetics, as well as the antioxidant and antimicrobial activities of eugenol. Using UV-VIS spectroscopy they determined the encapsulation efficiency and found higher encapsulation efficiencies of 95–98% for the formulations with only soy lecithin or whey protein. Bittencourt and co-authors also loaded eugenol by spray drying in low-lactose whey protein, bovine serum, rice bran protein, albumin, and carrageenan [40]. The best encapsulation of 80.5% was established for the formulation with bran protein, bovine serum albumin, and carrageenan. Encapsulation of clove oil in casein by the spray drying method with an encapsulation efficiency of 97.78% was also reported [41]. Woranuch and co-workers improved the thermal stability of eugenol by encapsulation into chitosan nanoparticles using an emulsion–ionic gelation cross-linking method with a highest encapsulation efficiency of 20% [42]. Paulo and Santos loaded eugenol in an ethyl cellulose polymer-based matrix by a double emulsion solvent evaporation technique and achieved an encapsulation efficiency of 94.7% [43]. Food polymers—zein, sodium caseinate, and pectin—were also used to encapsulate eugenol and stable nanoparticles were obtained via a heat- and pH-induced complexation process [44]. Shao et al. obtained eugenol-loaded nanoemulsions using the ionotropic gelation method with ultrasound-mediated emulsification and chitosan as a carrier with an encapsulation efficiency of up to 12% [45].
Myo-inositol is an isomer of cyclohexanehexol, which is biosynthesized from glucose in our body [46]. Impressive benefits from the intake of inositol have been reported like relieving symptoms of polycystic ovary syndrome, lowering the serum insulin level, and improving insulin resistance [47]. In spray drying powder technology, as a member of the group of sugar alcohols, it acts as a sweetening, hydrophilizing, and powder structure-forming agent. Aerosil, a colloidal silicon dioxide, is widely used as an excipient in pharmaceutical formulations, food products, and cosmetics [48]. In spray drying powder technology, colloidal silicon dioxide acts as a dispersion stabilizer, pore-forming, and powder gliding agent.
This study aims to increase the water solubility of eugenol by encapsulation in Soluplus® and Lutrol F 127 using green, high-yield low-temperature spray drying technology using pharmacopoeial and GRAS (generally recognized as safe) listed active substances and excipients. The solvent selected for the spray drying solutions was water, which is the greenest possible solvent. Formulations containing myo-inositol and Aerosil® 200 were prepared to study how the quantity of the entrapped eugenol, the morphology, and the size of the spray-dried particles will be influenced. Additionally, the effect of the spray drying inlet/outlet temperatures was also considered for selected compositions using the following combinations 90/45 °C, 80/41 °C, and 70/30 °C. The amount of the embedded eugenol in the obtained spray-dried samples was estimated using UV/VIS spectroscopy and the dissolution profiles of selected spray-dried powders were compared. The morphology was studied via scanning electron microscopy (SEM) and the size of the particles in a water solution was determined by dynamic light scattering (DLS). The samples were also characterized using Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC).
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Materials and Reagents
Eugenol (AlfaAesar, 99 % purity), Soluplus®, and Lutrol F 127 (BASF SE, Ludwigshafen, Germany) were used (Figure 10). Ethanol Absolute 99.8+%, Certified AR for Analysis (Fisher Chemical™), myo-inositol, and Aerosil 200 (colloidal silica) were also used.
