The global nutraceutical industry is one among the fastest–growing industries today. In 2019, the worldwide nutraceutical ingredients market price was estimated at USD 152.0 billion and was projected to succeed in USD 228 billion by 2025, at a CAGR of seven . a number of the key factors driving this growth are rising awareness about better dietary sources, growing aging population, and increasing prevalence of chronic diseases.

The terms ‘’nutraceuticals’’ and ‘’dietary supplements’’ are often used interchangeably. Although there's no regulatory definition of nutraceuticals, the term generally implies purified components derived from botanical sources and alleged to have medicinal properties to treat and cure acute and chronic disorders. Dietary supplements, on the opposite hand, are clearly defined by regulatory bodies. consistent with the Dietary Supplement Health and Education Act (DSHEA), a dietary supplement

is a product (other than tobacco) that's intended to supplement the diet that bears or contains one or more of the subsequent dietary ingredients: a vitamin, a mineral, a herb or other botanical, an amino acid, a dietary substance to be used by man to supplement the diet by increasing the entire daily intake, or a concentrate, metabolite, constituent, extract, or combinations of those ingredients;
is intended for ingestion in pill, capsule, tablet, or liquid form;
is not represented to be used as a standard food or because the sole item of a meal or diet;
is labeled as a dietary supplement;
includes products like an approved new drug, certified antibiotic, or licensed biologic that was marketed as a dietary supplement or food before approval, certification, or license (unless the Secretary of Health and Human Services waives this provision).
Nutraceuticals are different from dietary supplements in that:

nutraceuticals are alleged to aid within the prevention and/or treatment of disease/disorder additionally to supplementing the diet
nutraceuticals must be represented either within the sort of a standard food or a sole sort of meal or diet
Typical nutraceuticals include:

Plant materials
Extracts from plants
Foods containing additional active ingredient aside from vitamin or minerals and providing other health benefits which are proven scientifically
Extracts from marine sources
Products derived from animals and microorganisms
Why is manufacturing nutraceuticals challenging?

Sourcing and standardisation

The biggest drawback of plant-sourced products is that the lack of reproducible activity. This variation within the biochemical profile can occur thanks to several reasons, for instance , plants harvested at different times and locations, differences in plant variety, variations within the extraction methods also as in assays employed for activity determination ꟷall these factors affect reproducibility. Also, the biological activity of plants may be a results of additive or synergistic interaction with the opposite components. Still, taking specific measures like standardisation of qualitative and quantitative methods for bioactive content determination and optimisation and control of plant growing conditions can make the manufacturing cost-effective without compromising quality.

Physicochemical properties

Usually, herbal products are a mix of several constituents that are liable for the activity. Also, the processing of those products involves variety of variables like.

Source and quality of staple
Harvesting method
Storage and transportation
Mode of extraction
Polarity of the extracting solvents
Stability of constituents
Particle shape and size
All these variables can make manufacturing operations difficult. as an example , powders of barks and roots are usually needle-shaped fibers that inhibit flow during processing. Such powders require milling to get fine size particles before blending. Besides particle shape and size, there are other factors like moisture absorption, oiliness, waxy consistency, and electricity that also cause flow inhibition. to bypass this problem, glidants like silica , calcium silicate, and talc are often added to the powders. Being of extremely small size, glidants coat the surface of larger particles and reduce friction, absorb excess moisture, and thus, improve flow. Such smooth–flowing powders further facilitate processing on high-speed tableting or encapsulation machines.

The form of botanical raw materials, starting from crude powdered leaf or root to finely powdered extract, also creates challenges during formulation development. Hygroscopic herbal powders cause poor flow and stability issues.

Minerals within the formulation not only impart poor taste but also react with nutrients and vitamins within the presence of warmth and moisture, causing bioavailability, solubility, and tolerability issues. Different techniques like microencapsulation, taste-masking, stabilisation with carriers (hydrophilic proteins, polysaccharides), chelation with a complexing agent, micro pulverisation, and liposome applications are often wont to overcome the challenges related to mineral fortification. The recommended dose of trace minerals is typically in micrograms which also poses a challenge in preparing a uniform blend for typical batch size.

Certain phytochemicals like phytosterols clog the mill during milling operation due to their waxy nature and thus exhibit poor flow property. they're also difficult to compress due to their low bulk density. Hence, such phytochemicals are usually formulated as capsules.

Microbiological challenges

Most of the raw materials utilized in the nutraceutical formulations are either derived from plants or animals. Therefore, it becomes imperative to put strict controls on the bioburden (natural microbial count) of raw materials and follow rigorous microbiological process controls throughout the manufacturing process. Such measures not only keep cross-contamination to a minimum but also ensure acceptable microbial quality within the final product. Further, the staple suppliers must be evaluated from a microbiological perspective.

Analytical challenges for dietary supplement

The inherent variability of the plant components and their specific nature poses another set of problems when it involves their analysis, as are often seen within the following examples.
Change in cyanocobalamin manufacturer led to method interference with other vitamins.
Interaction of minerals with vitamins like ascorbic acid, vitamin D, and vitamin A results in oxidation/reduction reactions.
Use of coated vitamins and minerals to minimise interaction resulted in poor analyte recovery.
Trace amounts of vitamins or minerals within the presence of huge quantities of other analytes/matrix led to poor recovery/detectability.
Different types of herbal formulations
An array of techniques is employed to extract the active component from the plant materials. A typical method is to grind or steep the plant parts (macerate) containing the medicinal component and soak them during a liquid (menstruum) for extraction. Following are the various methods employed for herbal products.


Infusions are solutions of botanical principles obtained by soaking the powdered botanical in hot or cold water or ethanol or hydroalcoholic mixture for a specified time and straining. Typically, infusions are 5% in strength.


Decoctions are solutions of botanicals prepared by boiling in water for at least 15 minutes and straining. Typically, decoctions are 5% in strength.


Tinctures are solutions of botanical substances in alcohol and water obtained by extracting the powdered, flaked, or sectioned botanical.


These are powdered extracts of the active component prepared by evaporating the extraction solvent.

Fluid extracts

A fluid extract is an alcoholic liquid extract made by percolation of a botanical so that 1 ml of the fluid extract represents 1 g of the botanical.

Granulation techniques

Spray drying

For most of the plant extracts, spray-drying is employed as a preliminary step before proceeding to granulation. Since spray-dried plant extracts usually exhibit alittle particle size and poor flow, they often cause weight variation and poor content uniformity within tablets. employing a proper granulation technique, the particle size are often increased to enhance the flow .

Direct compression

The selection of the direct compression technique depends upon the number of ingredients within the formulation. it's not a feasible method for dietary supplements which contain quite one plant or mineral ingredient. Direct compression is suggested for moisture-sensitive herbal actives.
The use of other granulation techniques, including fluid bed granulation, wet granulation, and roller compaction, depends upon the character of the plant materials and therefore the production feasibility.

Storage and stability
Phytochemicals are generally labile substances and hence, must be stored at low temperatures throughout the manufacturing process. Dry powders stored for an extended time may have altered active content concentration, and it must be accounted for when producing the ultimate dosage form. Different extraction methods and processing steps can impact the physical and chemical properties of the ultimate plant extract. Manufacturers must have a radical physicochemical characterisation of the plant extracts obtained from multiple suppliers.

Manufacturing plant-based nutraceuticals have always remained a difficult task for manufacturers. the various nature of the plant materials, variability within the active component quantity, and therefore the associated microbial load make the general manufacturing operations quite complex, demanding careful planning of the whole production process. However, the extensive knowledge of the physicochemical properties of the active ingredients can significantly relieve the manufacturers, guiding them in selecting the proper granulation technique for the merchandise and setting appropriate quality control .


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