Novel technologies to enhance solubility of food-derived bioactive compounds: A review
Introduction
In light of consumer perception and preferences toward health promoting foods, the development of new functional food is a leading trend in food industry. Various bioactive compounds have been obtained from natural sources and classified into different categories based on their chemical structure and functions: phenolic compounds, vitamins, carotenoids, alkaloids, and organosulfur compounds (Hamri et al., 2011, Jeong et al., 2015, Lim et al., 2017). Many of bioactive components were identified and isolated from vegetables, fruits, legumes, oils, nuts, and whole grains and have shown numerous beneficial effects on human health including antioxidant, anti-inflammatory, antibacterial, and immunomodulatory activities (Hsieh et al., 2015, Imm et al., 2014, Kris-Etherton et al., 2002). Therapeutic effects of these compounds for instance; allicin (from garlic), curcumin (from turmeric), catechines (from tea polyphenols) helps to prevent diseases including cancer, cardiovascular illness, neuronal degenerative diseases, diabetes, etc. (Pandey and Rizvi, 2009, Pham-Huy et al., 2008). However, the incorporation of these bioactive molecules into commercial food products is a challenging task due to their poor stability and low rate of solubility (Lee et al., 2015, Teleki et al., 2013, Yousuf et al., 2016). Furthermore, the therapeutic health effects of orally administered bioactive compound depend on several factors such as solubility in an aqueous environment and permeability through the epithelial cell membrane, concentration of bioactive compounds in blood/plasma and molecular interactions in gastro intestinal fluids. Numerous technologies and novel food delivery systems have been developed to overcome these solubility and permeability issues.
Solubility is one of the important parameters to achieve the desired concentration of drug/bioactive substance in systemic circulation for therapeutic response (Vemula, Lagishetty, & Lingala, 2010). The aqueous solubility is a major indicator for the solubility in the intestinal fluids and its potential contribution to bioavailability issues (Stegemann, Leveiller, Franchi, De Jong, & Lindén, 2007). Extracted bioactive compounds from plant resources can be used in cosmetics and medicines. For instance, antioxidants derived from plant sources are used in skin and hair care products that affect the biological function of skin and hair and enhance the beauty and health. More than 40% of newly developed drugs in the pharmaceutical industry are practically insoluble in water (Savjani, Gajjar, & Savjani, 2012). The limited aqueous solubility of these compounds results in a low absorption rate in the gut, leading to decreased bioavailability but increased side effects such as gastrointestinal tract irritation because of using high doses or high concentration of surfactants in emulsions (Sivakumar et al., 2014, Wang et al., 2014). In this context, powerful solubilizing methods have been developed for improved absorption and bioavailability with lower manufacturing cost. The solubility of bioactive compounds can be altered through particle engineering techniques and several formulation approaches. Particle engineering techniques are developed to produce defined particles to modify phycochemical properties of poorly soluble substances (Kale et al., 2014, Koshy et al., 2010). Particle engineering, which includes mechanical particle-size reduction techniques (wet-milling, dry-milling, and high-pressure homogenization), cryogenic particle engineering techniques (lyophilization, spray freezing), and other micro/nanoparticle preparation methods such as nano-precipitation, supercritical fluid processing (Kale et al., 2014, Morales et al., 2016). In formulation strategy, the drugs or bioactive compounds are formulated in solutions which consist of water/oil, stabilizer, drug, and other excipients. General formulations include solid formulations, lipid formulations (for example, emulsion based drug delivery systems) and amorphous formulations (example, amorphous solid dispersions) (Merisko-Liversidge et al., 2003, Pouton, 2006). These formulations are prepared using spray drying, milling and other techniques.
The amount of solute that can be dissolved in a solvent depends on various factors, including temperature, pressure, chemical nature, and physico-chemical forms of substances.
The smaller the particle size, the greater the dissolution rate. The thickness of the diffusion layer around each particle reduced with particle specific surface area increases. Therefore, a decrease in particle size with high surface area results in an increase in dissolution rate (Mosharraf and Nyström, 1995, Niebergall et al., 1963). Furthermore, symmetrical molecules are less soluble than unsymmetrical ones (Pinal, 2004). Solubility of hydrophobic molecules can be increased by disruption of molecular symmetry without any increase of molecular weight (Ishikawa & Hashimoto, 2011).
The solubility for many solids and liquids usually increases with temperature increases. The kinetic energy increases with temperature and it allows the solvent molecules to more effectively break apart the solute molecules that are held together by intermolecular attractions (Feriyanto, Idris, & Sebayang, 2014).
Generally greater molecular weight substance will be less soluble. In the case of organic compounds, the solubility increases with the amount of carbon branching. The solubility of branched polymer will be higher than the linear polymer of same molecular weight. Because the branched chains have smaller radius of gyration (Rg), and decreased degree of chain entanglement, thus the branched-chain molecules exhibit smaller volume/dimension in solution and dissolve more readily (Harris, 2006, Jadhav and Pandey, 2013, Ravve, 2013).
Generally Polar solutes/substances are dissolve in polar solvents, and nonpolar substances dissolve in nonpolar solvents. The solvent particles hold the solute particles by intermolecular attractive forces. Polar and ionic solutes generally cannot dissolve in non-polar solvents and vice versa.
Amorphous forms of bioactives have greater aqueous solubility than the crystalline form. Polymorphs have different solubilities. The physical arrangements of the constituents in the crystal lattice have immense potential to influence the physicochemical properties of the bioactive substance and subsequently therapeutic outcomes. Therefore, the study of polymorphic forms has become important (Raza, Kumar, Ratan, Malik, & Arora, 2014).
The pH of a solution can influence the solubility of solute, therefore, the state of solute can be changed by changing the pH of solution. Many hydrophilic and lipophilic compounds exhibit different solubilities at different pHs. Weak acids and weak bases undergo an ionization reaction in solution. The ionized form of substance will be more soluble in water.
An emulsifier referred as surface-active compounds (i.e., surfactants) which contain both hydrophilic head group and lipophilic tail. The role of stabilizers or emulsifiers reduce the interfacial tension between the oil and water interface and increase the solubility (Krog, 1977).
Section snippets
Techniques for enhancing solubility of poorly water-soluble bioactive natural products
The solubility of poorly water-soluble bioactive compounds can be improved by modifying their physical and chemical properties. The physical and chemical modification of bioactive molecules may be achieved by various traditional and novel techniques, which are discussed in this review. Developing nanoparticle formulations in food industry by using nanotechnology is an innovative approach for substantial improvement of solubility and bioavailability of bioactive ingredients (Acosta, 2009,
Conclusions and future prospects
In early twentieth-century, functional foods were mainly focused to prevent or reduce the risk of nutritional deficiency diseases such as iron deficiency anemia, rickets, and scurvy diseases. The examples include vitamin C, vitamin D and iron fortified beverages. Later, consumer awareness of health and wellness are increased rapidly and they interested to consume healthier food products to avoid chronic diseases. Thus, food companies shifted their focus to develop fortified foods with various
Conflict of interest
The authors confirm that this article content has no conflict of interest.
Acknowledgement
This work was carried out with the support of “Cooperative Research Program for Agriculture Science & Technology Development (Project No. PJ012615)” Rural Development Administration, South Korea.
References (128)
Bioavailability of nanoparticles in nutrient and nutraceutical delivery
Current Opinion in Colloid & Interface Science
(2009)- et al.
A review on the use of cyclodextrins in foods
Food Hydrocolloids
(2009) - et al.
Polymeric amorphous solid dispersions: A review of amorphization, crystallization, stabilization, solid-state characterization, and aqueous solubilization of biopharmaceutical classification system class II drugs
Journal of Pharmaceutical Sciences
(2016) - et al.
α-Tocopherol nanosuspensions produced using a supercritical assisted process
Journal of Food Engineering
(2015) - et al.
Lipid – An emerging platform for oral delivery of drugs with poor bioavailability
European Journal of Pharmaceutics and Biopharmaceutics
(2009) - et al.
Solid self-microemulsifying system (S-SMECS) for enhanced bioavailability and pigmentation of highly lipophilic bioactive carotenoid
Powder Technology
(2015) - et al.
Hydrotropic extraction of bioactive limonin from sour orange (Citrus aurantium L.) seeds
Food Chemistry
(2008) - et al.
Increasing solubility of red bell pepper carotenoids by complexation with 2-hydroxypropyl-β-cyclodextrin
Food Chemistry
(2016) - et al.
Formulation of β-carotene by precipitation from pressurized ethyl acetate-on-water emulsions for application as natural colorant
Food Hydrocolloid
(2012) Cyclodextrins and their uses: A review
Process Biochemistry
(2004)
Inclusion compounds
Journal of Pharmaceutical Sciences
Preparation of a chemically stable quercetin formulation using nanosuspension technology
International Journal of Pharmaceutics
Nanosuspension for improving the bioavailability of a poorly soluble drug and screening of stabilizing agents to inhibit crystal growth
International Journal of Pharmaceutics
Antioxidant activity and bioaccessibility of size-different nanoemulsions for lycopene-enriched tomato extract
Food Chemistry
Thermal stability of the linoleic acid/α-and β-cyclodextrin complexes
Food Chemistry
Natural bioactives in cancer treatment and prevention
Biomed Research International
Spray freezing into liquid (SFL) particle engineering technology to enhance dissolution of poorly water soluble drugs: Organic solvent versus organic/aqueous co-solvent systems
European Journal of Pharmaceutical Sciences
Solubilization of poorly soluble compounds using 2-pyrrolidone
International Journal of Pharmaceutics
Nanoencapsulation of lutein with hydroxypropylmethyl cellulose phthalate by supercritical antisolvent
Chinese Journal of Chemical Engineering
Particle design using supercritical fluids: Literature and patent survey
The Journal of Supercritical Fluids
Drug nanocrystals of poorly soluble drugs produced by high pressure homogenisation
European Journal of Pharmaceutics and Biopharmaceutics
Pharmaceutical particle technologies: An approach to improve drug solubility, dissolution and bioavailability
Asian Journal of Pharmaceutical Sciences
Bioactive compounds in foods: Their role in the prevention of cardiovascular disease and cancer
The American Journal of Medicine
Modelling the solubility of solids in supercritical fluids with density as the independent variable
The Journal of Supercritical Fluids
Improving drug solubility for oral delivery using solid dispersions
European Journal of Pharmaceutics and Biopharmaceutics
Stability and solubility enhancement of ellagic acid in cellulose ester solid dispersions
Carbohydrate Polymers
Solid dispersion of quercetin in cellulose derivative matrices influences both solubility and stability
Carbohydrate Polymers
Nanoemulsion-based delivery systems for poorly water-soluble bioactive compounds: Influence of formulation parameters on polymethoxyflavone crystallization
Food Hydrocolloid
Overview of milling techniques for improving the solubility of poorly water-soluble drugs
Asian Journal of Pharmaceutical Sciences
Cyclodextrins as resveratrol carrier system
Food Chemistry
Nanosizing: A formulation approach for poorly-water-soluble compounds
European Journal of Pharmaceutical Sciences
The effect of particle size and shape on the surface specific dissolution rate of microsized practically insoluble drugs
International Journal of Pharmaceutics
Solid-state characterization and dissolution characteristics of gliclazide-β-cyclodextrin inclusion complexes
International Journal of Pharmaceutics
Nanoparticle formation of lycopene/β-cyclodextrin inclusion complex using supercritical antisolvent precipitation
The Journal of Supercritical Fluids
Dissolution rate studies II. Dissolution of particles under conditions of rapid agitation
Journal of Pharmaceutical Sciences
Characterization of antioxidant methylcellulose film incorporated with α-tocopherol nanocapsules
Food Chemistry
Optimization of α-tocopherol loaded nanocapsules by the nanoprecipitation method
Industrial Crops and Products
Novel ultra-rapid freezing particle engineering process for enhancement of dissolution rates of poorly water-soluble drugs
European Journal of Pharmaceutics and Biopharmaceutics
Applications for supercritical fluid technology in food processing
Food Chemistry
Colloidal delivery systems in foods: A general comparison with oral drug delivery
LWT – Food Science and Technology
Cyclodextrins as encapsulation agents for plant bioactive compounds
Carbohydrate Polymers
Formulation of poorly water-soluble drugs for oral administration: Physicochemical and physiological issues and the lipid formulation classification system
European Journal of Pharmaceutical Sciences
Nanoemulsion delivery systems: Influence of carrier oil on β-carotene bioaccessibility
Food Chemistry
Formation of nanoemulsions stabilized by model food-grade emulsifiers using high-pressure homogenization: Factors affecting particle size
Food Hydrocolloid
Crystallization of hydrocortisone acetate: Influence of polymers
International Journal of Pharmaceutics
Understanding the behavior of amorphous pharmaceutical systems during dissolution
Pharmaceutical Research
Solubilization patterns of lutein and lutein esters in food grade nonionic microemulsions
Journal of Agricultural and Food Chemistry
Past and future evolution in colloidal drug delivery systems
Expert Opinion on Drug Delivery
Cyclodextrins as food additives and in food processing
Current Nutrition & Food Science
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