Abstract
Background/Objectives: In this study, we present a green, scalable platform for the production of water-dispersible powders co-encapsulating the lipophilic bioactives curcumin (Cur) and eugenol (Eug) within the amphiphilic polymer Soluplus® (SP) via low-temperature spray drying.
Methods: The amount of Cur (1%, 5%, and 10%) and Eug (5%, 10%, 15%, and 20%) was varied to achieve single- and double-loaded water-soluble powders with the maximum amount of active substances. The powders containing a higher loading of Cur, 5% and 10% (and Eug), were obtained from water/ethanol mixtures (2:1 and 5:1 v/v ratio), while the formulation with 1% of Cur was spray-dried by using water as a solvent.
Results: By leveraging aqueous or aqueous–ethanolic feed systems, we achieved high loading of the bioactive substances—up to 10% Cur and 20% Eug (w/w)—while minimizing organic solvent use. Myo-inositol was incorporated as a stabilizing excipient to modulate particle morphology, improve powder flowability, and enhance redispersibility. Physicochemical characterization revealed nanoscale micellization (53–127 nm), amorphization of both actives as confirmed by XRD and DSC, and the absence of crystalline residue. Encapsulation efficiencies exceeded 95% for Cur and 93% for Eug. Dissolution tests demonstrated a rapid release from the 5% Cur/5% Eug formulation (>85% in 5 min), while higher-loaded single-formulations showed progressively slower release (up to 45 min).
Conclusions: This work demonstrates a robust and environmentally responsible encapsulation strategy, suitable for delivering poorly water-soluble phytochemicals with potential applications in oral nutraceuticals and pharmaceutical dosage forms.
Introduction
Curcumin (Cur) and eugenol (Eug) are natural bioactive substances possessing antioxidant, antifungal, antibacterial, anti-inflammatory, and anticancer properties [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20]. In particular, Cur is a crystalline substance with a bright orange–yellow color. It is one of the main constituents in the roots of Curcuma longa L., known in Asian cuisine as the spice turmeric [21]. Cur finds applications in food colorings and food additives. Eug is a light-yellow oil, which was first isolated in 1826 from cloves. Eug is used in pharmaceuticals, cosmetics, dentistry, the food industry, and agriculture as a pesticide [22,23]. Curcumin and eugenol have demonstrated significant potential for synergistic therapeutic activity. Recent studies suggest that combining curcumin’s anti-inflammatory and antioxidant properties with eugenol’s complementary antimicrobial and analgesic effects could enhance their pharmacological efficacy [24,25]. Co-encapsulation of both substances in a water-soluble formulation may thus provide improved bioavailability and an expanded therapeutic profile compared to their individual applications. However, both compounds are poorly water-soluble, limiting their bioavailability. The solubility of Cur and Eug in water can be increased by embedding them into polymer micelles through hydrophobic interactions [26,27,28]. Soluplus® (SP) is a graft copolymer composed of a hydrophobic part made of polyvinyl caprolactam and polyvinyl acetate and a hydrophilic segment of polyethylene glycol. SP is a copolymer with amphiphilic properties that forms nanosized structures in water. SP-based drug delivery systems, such as micelles, solid dispersions, nanosuspensions, and nanoemulsions, are widely investigated for improving the solubility and bioavailability of various therapeutic agents [29]. Spray drying is considered a green method for preparing powders that have fast solubility [30]. It is a rapid one-step method appropriate for temperature-sensitive compounds with an industrial application in pharmacy, chemistry, and food preparation [31,32,33,34,35,36,37]. Kamal et al. developed a curcumin-loaded powder by spray drying using SP and Neusilin® as solid carriers and ethanol as a solvent [38]. They formulated a self-emulsifying drug delivery system (SEDDS) by dissolving curcumin in sulforaphane, followed by mixing with cremophor EL and acconon CC6 (1:1 (w/w) mixture). The obtained powders, which were determined as the optimal composition with good flow characteristics, contained 0.9% of Cur based on the mass of the polymer. Other research also reported encapsulation of Cur using spray drying in ternary-composite wall materials like β-cyclodextrin, modified corn starch, maltodextrin, gelatin, pectin, tamarind gum, and inulin [39]; soy protein isolate nanocomplexes [40]; gum arabic [41]; gum arabic, sodium alginate and modified chitosan [42]; and maltodextrin, whey protein isolate and HI-CAP®100 (modified starch) [43].
Al-Akayleh et al. also investigated the effect of the solubility and dissolution rate of Cur using SP [44]. They reported a significant improvement in the solubility and in vitro release of curcumin. Besides the spray drying method, Cur-loaded Poloxamer® 188 and SP nanoparticles were obtained by antisolvent crystallization followed by freeze drying [45]. Curcumin-loaded mixed Soluplus/D-α-tocopheryl polyethylene glycol succinate (TPGS 1000) micelles were also reported [46]. Similarly, SP, Syloid® XDP 3150, Syloid® 244, and Poloxamer® 188 in combination with HPMC E5 (binary carrier) dispersions containing curcumin using the solvent evaporation method were prepared [47]. Another study also examined the interaction of SP with curcumin using UV/VIS, fluorescence, and infrared spectroscopies [48].
Using the spray drying method, Eug was encapsulated in various carriers such as maltodextrin and gum arabic, soy lecithin and whey protein, as well as rice bran protein, albumin, and carrageenan [49,50,51]. In a previous study, we obtained Eug-loaded Soluplus® and Lutrol F 127 spray-dried powders starting from a water dispersion [28]. We optimized the flowability of the formulations by the addition of myo-inositol (cyclohexanehexol isomer—a sweetener, hydrophilizing, and powder structure-forming agent) and Aerosil® 200 (amorphous colloidal silica—thermal stabilizer, pore-forming, anticaking, and powder gliding agent). As far as we know, formulations comprising both Cur and Eug are limited. Cur- and Eug-containing mucoadhesive gel for periodontal disease was recently formulated using Poloxamer 407 and Carbopol 934 [52,53].
However, there are currently no data in the literature on the simultaneous encapsulation of curcumin and eugenol in SP. The main objective of our study is to obtain water-soluble spray-dried powders, containing curcumin and eugenol, based on SP as a carrier. Although using water as a solvent is preferable, it was not possible to obtain stable feed solutions for spray-drying that contain more than 1% curcumin. Therefore, a mixture of water and ethanol was used for the high concentrations of the active ingredient(s). Combining water with water-miscible solvents such as ethanol is advantageous for improving the solubility of poorly water-soluble therapeutic agents, as well as for adjusting the final boiling point, thereby enabling spray drying at lower temperatures [54]. We minimized the use of organic solvents, which, on the one hand, guarantees an environmentally friendly approach and, on the other, makes the process more economically viable.
Optimization of the conditions for preparing Cur/Eug-loaded powders was performed by varying the amount of active ingredients, the water/ethanol ratio (2:1 and 5:1), and the concentration of the spray drying feed solutions. The ultimate goal of the series of experiments was to develop powders containing the maximum amount of active ingredients, which are water-soluble and form stable Cur/Eug-loaded colloidal nanoparticles upon dissolution in water. Several studies have reported the impressive benefits of inositol intake, such as alleviating symptoms of polycystic ovary syndrome, lowering serum insulin levels, and improving insulin resistance approximately twice as well as pioglitazone or metformin, which are used as therapies for patients with glucose intolerance [55]. Therefore, as in our previous study [28], we optimized the composition by the addition of myo-inositol to improve the flowability and solubility of the powders.
The powders were characterized using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (ATR-FTIR), X-ray diffractometry (XRD), and differential scanning calorimetry (DSC). The zeta potential, particle size, and dispersity index of the colloidal solutions after dissolving the powders in water were determined by dynamic light scattering (DLS). UV–VIS spectroscopy was used to evaluate the amount of encapsulated curcumin and eugenol.
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Materials
Curcumin (Fluorochem, Glossop, UK, 95% purity), Eugenol (AlfaAesar GmbH & Co. KG, Karlsruhe, Germany, 99% purity), Soluplus® (BASF SE, Ludwigshafen, Germany), myo-inositol (AlfaAesar GmbH & Co. KG, Karlsruhe, Germany, 98.0% purity), and Aerosil® 200 (Evonik Operations GmbH, Essen, Germany), were used for preparing the formulations (Figure 17). Distilled water and Ethanol Absolute 99.8%, Certified AR for Analysis (Fisher Chemical™, Pittsburgh, PA, USA), were used as a solvent for the preparation of the feed spray drying dispersions, as ethanol has also been used for the curcumin and eugenol assay.
Koleva, I.Z.; Kamenova, K.; Petrov, P.D.; Tzachev, C.T. Water-Soluble Formulations of Curcumin and Eugenol Produced by Spray Drying. Pharmaceuticals 2025, 18, 944. https://doi.org/10.3390/ph18070944
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