Waleed Mustafa
Bioavailability of Nutraceuticals
Bioavailability indicates the rate and extent at which the active ingredients enter into the systemic circulation and are delivered to the target site. This determines the effectiveness of a given dose usable by the body and is the defining indicator of level of absorption. There are many factors that affect the bioavailability of an active nutraceutical ingredient some of which are stated below:
- Pharmaceutical factors: The formulation/nature/components of a nutraceutical can greatly influence its bioavailability. This includes the type of active ingredient used, its chemical properties, and the delivery mechanism. For instance, the solubility and stability of an ingredient can affect how well it is absorbed in the gastrointestinal tract [1]. Additionally, the presence of excipients or other compounds in the formulation can enhance or inhibit absorption, which is a key consideration for formulators aiming to deliver potent and rapidly absorbed ingredients [1].
- Administrative Route: Different methods, such as oral, sublingual, or intravenous delivery, can lead to varying absorption rates and extents. Oral formulations, for instance, must survive the harsh conditions of the gastrointestinal tract (acidic pH) before entering systemic circulation, which can limit their bioavailability compared to other routes. The design of the study that evaluates bioavailability, such as whether it involves single or multiple doses, also affects outcomes by influencing the pharmacokinetics involved [3].
- Patient related factors: Individual variability among patients also plays a crucial role in bioavailability. Factors such as age, gender, genetic makeup, and overall health can impact how a nutraceutical is absorbed and metabolized. For example, patients with certain metabolic disorders may process active ingredients differently, leading to variations in effectiveness [2]. Furthermore, lifestyle choices, including diet and medication use, can also influence bioavailability by altering gastrointestinal conditions or competing for absorption pathways [3].
Main challenges in Bioavailability of Nutraceuticals formulations:
- Solubility issues: The primary challenge among majority ingredients is their poor solubility. Nearly 40% of new molecular entities developed in the pharmaceutical industry suffer from solubility and bioavailability issues, which hinder their therapeutic effectiveness. Poorly soluble compounds often have limited absorption in the gastrointestinal tract, significantly affecting their systemic availability. This challenge is compounded by physiological barriers such as intestinal tight junctions, transporters, and enzymatic barriers that further limit the oral absorption of drugs and nutraceuticals [4].
- Nutraceutical formulation: Formulators face the challenge of delivering potent ingredients that can be quickly absorbed by the body to maintain consumer appeal [1]. Strategies to enhance solubility, such as using lipid-based nanocarriers or innovative delivery systems, are being explored to overcome these obstacles [4]. Moreover, issues related to the stability of active ingredients can lead to degradation before they exert their desired effects in the body, making formulation complexity a key consideration for developers.
- Individual Variability: The health and habits of the person taking the nutraceutical significantly defines the bioavailability of the nutraceutical. This is because of factors such as gut microbiome composition, dietery patterns and genetic predispositions influence the absorbption and utilization of the nutraceutical.
Strategies to imporve Bioavailability:
- Delivery Systems: Major innovations in delivery systems can play a critical role in improving the bioavailability of the active ingredients. Bio-based delivery systems can potentially stabilize active ingredients which can prolong their life in the systemic routes. This includes developing lipid based formulations, micelles, core shell particles etc, where a biopolymer can engulf or encapsulate the poorly soluble or degradable material prolonging its life and release profile in the body. There is plethora of literature available on design of such nano and micro particles for delivery and therapy.
- Technological systems: Promising technologies such as 3D bioprinting or, in current case, electrospraying can lead the revolution of using nutraceuticals for nano/micro sized formulations having multiple ingredients produced in a single step eleminating multiple synthesis and stabilizing processes. The advantages of electrospraying have been discussed earlier breifly.
Electropspraying: A single step production method of Nano/Microparticles for Nutraceuticals
Electrospraying, a technique rooted in electro-hydrodynamic atomization, has evolved significantly since its inception. The process, which utilizes electrical forces for liquid atomization, has gained traction within various industries, particularly in food nanotechnology and the encapsulation of nutraceuticals. The process of spraying using electrical field enables the production of micro and nano sized particles with controlled properties. Furthemore, multiple materials can be arranged via core-shell method or encapsulation method for many applications such as safely delievering essential compounds to their target site e.g., biomedicine.
These advancements have made electrospraying a revolutionizing method for encapsulating nutraceuticals, such as vitamins, minerals and phytochemicals as nutritional supplements, allowing for better stability and bioavailability of active compounds [5]. By adjusting parameters such as flow rate and voltage, researchers have optimized the electrospraying process for various applications, including food ingredient stabilization, drug delivery, and film coating [6]. The growing understanding of nutraceuticals, defined as food-derived products offering health benefits beyond basic nutrition, further propelled the adoption of electrospraying techniques. By the 2000s, the emphasis on health and wellness, combined with increased consumer interest in dietary supplements and functional foods, encouraged manufacturers to seek innovative methods to enhance the efficacy of nutraceuticals. As a result, electrospraying has been increasingly recognized for its ability to produce encapsulated nutraceuticals with improved performance characteristics [6][7][8]. Currently, electrospraying is considered a critical technology in the nutraceutical industry, continuously evolving to meet the demands for more effective health and multi functional products.
Electrospraying mechanisms:
Electrospraying, a method of electrohydrodynamic atomization, utilizes a voltage-driven technique to generate particles or fibers from a liquid solution, typically a polymer solution, emulsion, or dispersion. The fundamental mechanism of electrospraying involves the application of a high voltage to a liquid jet, which results in the formation of a charged droplet, typically of polymers, that can be atomized into smaller particles.
Taylor cone formation: The process begins when a liquid is ejected through a capillary needle/nozzle or bulging surface resulting in a small pool at an edge or tip under the influence of an applied electric field. The electrical charges accumulate on this surface, causing the liquid to deform into a conical shape known as the Taylor cone. This deformation occurs because the surface tension of the liquid must balance the electrical forces acting on it [9]. Once the electrical forces surpass the surface tension, the liquid jet is ejected from the tip of the Taylor cone.
Jet instability and droplet formation: After exiting the surface, the liquid jet experiences Rayleigh-Plateau instability which further breaks down into smaller droplets due to Columbic repulsion and surface tension as it is moving towards the collector. The droplet size is optimizable with the process parameters including solution flow rate, voltage and working distance between nozzle and collector surface. Major optimizations can be achieved via optimizing solution parameters such as viscosity, choice of particles and molecular weights. All these factors combined can give a particle sizes ranging from 20 nm upto 30 µm [9].
Advantages of Electrospraying for Nutraceuticals:
Main advantages of using electrospraying system compared to conventional methods are pointed below:
- Enhanced Bioavailability: The process of nanoencapsulation protects sensitive compounds from environmental degradation, such as moisture and thermal exposure, ultimately enhancing their stability and functional properties [9]. This is particularly important for bioactives that exhibit poor solubility or low permeability, as electrospraying can mask undesirable properties and facilitate controlled release, improving the effectiveness of the nutrients when ingested[10].
- Dry particles: Generation of dry particles in a single step and minimizes agglomoration due to droplet repulsion allowing better dispersion.
- Scalability: Easily scalable to multi-nozzle system or open surface systems for pilot and industrial setups making it feasible for nutraceutical, pharmaceutical and food processing industries.
- Versatility: Fine tuning of particle morphology possible allowing various active ingredients to be encapsulated or protected simulatenously. Additionally, morphology design is possible using multiple features of the spraying process including 2-shell or multi-shell core schemes.
- Environmental and Economic impact: Electrospraying is a highly cost effective and simple method compared to other conventional nanoparticle production techniques. It’s high efficiency also ensures its lower impact as many natural ingredients can be sprayed using water based solutions which makes the process green and environment friendly.
References
[4]https://www.clinicaltrialsarena.com/buyers-guide/leading-bioavailability-studies-companies/
[5]https://www.mdpi.com/1420-3049/28/8/3592
[7]https://www.chemijournal.com/archives/?year=2019&vol=7&issue=5&ArticleId=7105
[8]https://www.canadagazette.gc.ca/rp-pr/p2/2022/2022-07-06/html/sor-dors146-eng.html
[10]https://atlantiaclinicaltrials.com/blog/regulatory/are-nutraceuticals-regulated-by-the-fda