Microparticles of greenish-brown propolis extract: phytochemical, physicochemical characterisation and in vitro dissolution profile

Abstract

The low solubility of propolis in water and its limited bioavailability reduce the effectiveness of bioactive compounds, demonstrating the necessity of techniques that can overcome these limitations. Spray-drying is a promising approach to overcoming these challenges. In this study, microparticulate systems containing greenish-brown propolis extract were produced and characterised. The following analyses were performed: antioxidant activity; total phenol and flavonoid content; UV–Vis and FTIR spectroscopy; thermal analysis; scanning electron microscopy (SEM); and in vitro dissolution tests. The extracts and microparticles exhibited a total flavonoid content of 5.15% and 1.13%, respectively (equivalent to quercetin), and a total phenol content of 14.16% and 4.81% (equivalent to gallic acid). Antioxidant activity was assessed using the IC₅₀ method, yielding values of 13.77 µg.cm⁻³ for the propolis extract and 60.80 µg.cm⁻³ for the propolis microparticles. UV–Vis and FTIR analyses confirmed the encapsulation of the phenolic compounds, while thermal analysis demonstrated the thermal protection provided by the excipients. In vitro dissolution tests showed that the microparticulate system released an average of 66% of flavonoids in different dissolution media over 240 min, highlighting their low solubility in water. These results suggest that adding pharmacotechnical adjuvants could enhance the dissolution of active compounds, thereby expanding the therapeutic potential of encapsulated brown-green propolis in pharmaceutical and nutraceutical applications.

Introduction

Propolis is a complex mixture of resinous and balsamic substances collected by bees, primarily from the Apis mellifera species, from tree branches, flowers, pollen, buds and exudates. The bees then add their own salivary secretions and enzymes, resulting in a mixture of different herbal exudates, salivary enzymes and bees wax, which is used to protect the hive of insects, virus, bacteria and fungi [1].

Propolis’s immunological protection and antioxidant properties derive from its bioactive phytochemical components. Several compounds have been identified in propolis, with the composition varying depending on the area of production. These include phenolic acids, flavonoids, esters, diterpenes, sesquiterpenes, lignans, aromatic aldehydes, alcohols, amino acids, fatty acids, vitamins and minerals [2].

In this context, research into uncatalogued greenish-brown propolis from mountainous Alagoas, Brazil, highlights its unique biological profile, justifying its potential inclusion in national classification systems and future geographical indication applications [3]. Addressing the lack of previous literature, a pioneering study characterised seasonal influences on key chemical markers (flavanones, flavanonols, flavones, flavonols and hydroxycinnamic acids) and utilised multivariate analysis to correlate this composition with in vitro antioxidant, antimicrobial and antileishmanial potential of this type of propolis [3].

Despite its great therapeutic potential, propolis’s low solubility in water limits its application in several areas, hindering the bioavailability of its chemical compounds such as polyphenols [4]. Currently, powder engineering is being increasingly applied in the pharmaceutical sector to optimise the physicochemical, micromeritic and/or pharmacokinetic properties of drugs and bioactive compounds to increase their efficacy [5].

Spray-drying is one of the most widely used techniques for this purpose, as it is a low-cost, fast, effective and accessible microencapsulation technique that lends itself well to industrialisation. Furthermore, it enables continuous production [4, 5]. This technology is also advantageous for protecting bioactive compounds that are sensitive to degradation by free radicals, light and oxygen [6]. Spray-dried powders have low water content, have excellent reconstitution characteristics and are suitable for transportation and storage. The main protective function of this technology is to form a membrane or shell around the particles or droplets of the active ingredients being encapsulated (the core material) [4,5,6,7]. Therefore, an effective encapsulating agent should possess emulsifying and film-forming properties, be low in hygroscopicity, have a low viscosity even at high solids content, be resistant to the gastrointestinal tract, be biodegradable and non-toxic, be economical, have a neutral flavour and be soluble in aqueous solvents [8].

Dosage forms obtained by spray-drying include microparticulate systems, which fall into two main categories: microspheres, where the active compound and raw material are homogeneously dispersed or dissolved; and microcapsules, which have a membrane surrounding and delimiting the core, which can be solid, liquid or gas, where the active ingredient is stored [8].

In this context, encapsulation strategies have been explored in the literature to optimise the functionality of propolis, using various polymer matrices and synthesis methods. The use of biopolymers such as inulin, alginate, pectin, and chitosan via spray-drying has proven effective in promoting controlled release in the gastrointestinal tract, increasing the bioavailability of phenolic compounds compared to the free extract [9]. Additionally, the use of gelatin and sodium alginate allowed for encapsulation efficiencies of 92%, resulting in microcapsules with high solubility, rapid dissolution and low hygroscopicity [10]. In the context of complex coacervation, the interaction between chia mucilage and gelatin proved to be a promising strategy for stabilising bioactive compounds, aiming at the development of functional foods with potential health benefits [11]. Specifically, regarding Brazilian biodiversity, the use of biopolymers to encapsulate red propolis from Alagoas via spray-drying produced particles with thermal stability and optimised dissolution and antioxidant activity profiles, reinforcing the potential of these systems to modulate the release of regional ingredients [12].

However, the low bioavailability and variability in potency of propolis-containing extracts pose significant obstacles to their clinical application, as does the growing demand for natural and efficient alternatives in the pharmaceutical field. Against this backdrop, the formulation of microparticulate systems using an ethanolic extract of brown propolis emerges as an innovative strategy to optimise the release and absorption of bioactive compounds. This study aims to develop such systems containing greenish-brown propolis by spray-drying and evaluate their in vitro dissolution and thermal profiles and antioxidant capacity. The study will deepen our understanding of microparticulate systems and contribute to the development of new propolis-based pharmaceutical formulations.

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Chemicals and materials

Analytical standards for gallic acid, quercetin and naringenin, as well as the free radical DPPH (2,2-diphenyl-1-picrylhydrazyl) and Folin–Ciocalteu reagent, were purchased from Sigma-Aldrich (St. Louis, Missouri, USA). Biopolymers, including gelatin, starch, colloidal silicon dioxide (Aerosil® 200) and microcrystalline cellulose, were purchased from Synth® (São Paulo, Brazil). The excipient croscarmellose sodium (Explocel®) was purchased from Blanver© (São Paulo, Brazil). Reagents used for phytochemical analysis, antioxidant activity and dissolution studies, including sodium carbonate, calcium carbonate, aluminium chloride hexahydrate, methanol, equimolar phosphate buffer solution (pH 6.8), 1% polysorbate 60, 1% sodium lauryl sulphate and 0.05 M hydrochloric acid (pH 1.5), were purchased from Exodo Científica (São Paulo, Brazil).

de Oliveira Silva, L.R., Freitas, J.M.D., Oliveira, J.V.L. et al. Microparticles of greenish-brown propolis extract: phytochemical, physicochemical characterisation and in vitro dissolution profile. J Therm Anal Calorim (2026). https://doi.org/10.1007/s10973-026-15885-7