Manufacturing plant-based products and nutraceuticals



The global nutraceutical industry is one of the fastestgrowing industries today. In 2019, the global nutraceutical ingredients market value was estimated at USD 152.0 billion and was projected to reach USD 228 billion by 2025, at a CAGR of 7%. Some 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 is no regulatory definition of nutraceuticals, the term generally implies purified components derived from botanical sources and purported to have medicinal properties to treat and cure acute and chronic disorders. Dietary supplements, on the other hand, are clearly defined by regulatory bodies. According to the Dietary Supplement Health and Education Act (DSHEA), a dietary supplement 

  • is a product (other than tobacco) that is intended to supplement the diet that bears or contains one or more of the following dietary ingredients: a vitamin, a mineral, a herb or other botanical, an amino acid, a dietary substance for use by man to supplement the diet by increasing the total daily intake, or a concentrate, metabolite, constituent, extract, or combinations of these ingredients; 
  • is intended for ingestion in pill, capsule, tablet, or liquid form; 
  • is not represented for use as a conventional food or as the sole item of a meal or diet; 
  • is labeled as a dietary supplement; 
  • includes products such as 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 supposed to aid in the prevention and/or treatment of disease/disorder in addition to supplementing the diet 
  • nutraceuticals must be represented either in the form of a conventional food or a sole form of meal or diet  

Typical nutraceuticals include: 

  • Plant materials  
  • Extracts from plants 
  • Foods containing additional active ingredient apart 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 the lack of reproducible activity. This variation in the biochemical profile can occur due to several reasons, for example, plants harvested at different times and locations, differences in plant variety, variations in the extraction methods as well as in assays employed for activity determination all these factors affect reproducibility. Also, the biological activity of plants is a result of additive or synergistic interaction with the other components. Still, taking specific measures such as 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 mixture of several constituents that are responsible for the activity. Also, the processing of these products involves a number of variables such as 

  • Source and quality of raw material 
  • 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. For instance, powders of barks and roots are usually needle-shaped fibers that inhibit flow during processing. Such powders require milling to generate fine size particles before blending. Besides particle shape and size, there are other factors such as moisture absorption, oiliness, waxy consistency, and static electricity that also cause flow inhibition. To circumvent this problem, glidants such as silicon dioxide, calcium silicate, and talc can be 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 smoothflowing powders further facilitate processing on high-speed tableting or encapsulation machines.  

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

Minerals in the formulation not only impart poor taste but also react with nutrients and vitamins in the presence of heat and moisture, causing bioavailability, solubility, and tolerability issues. Different techniques such as microencapsulation, taste-masking, stabilisation with carriers (hydrophilic proteins, polysaccharides), chelation with complexing agent, micro pulverisation, and liposome applications can be used to overcome the challenges associated with mineral fortification. The recommended dose of trace minerals is usually in micrograms which also poses a challenge in preparing a homogenous blend for typical batch size.  

Certain phytochemicals such as phytosterols clog the mill during milling operation because of their waxy nature and therefore exhibit poor flow property. They are also difficult to compress because of their low bulk density. Hence, such phytochemicals are usually formulated as capsules.       

  • Microbiological challenges 

Most of the raw materials used in the nutraceutical formulations are either derived from plants or animals. Therefore, it becomes imperative to place 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 in the final product. Further, the raw material suppliers must be evaluated from 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 comes to their analysis, as can be seen in the following examples. 

  • Change in cyanocobalamin manufacturer led to method interference with other vitamins. 
  • Interaction of minerals with vitamins such as ascorbic acid, vitamin D, and vitamin A leads to oxidation/reduction reactions. 
  • Use of coated vitamins and minerals to minimise interaction resulted in poor analyte recovery. 
  • Trace amounts of vitamins or minerals in the presence of large quantities of other analytes/matrix led to poor recovery/detectability.   

Different types of herbal formulations 

An array of techniques is used 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 in a liquid (menstruum) for extraction. Following are the different methods employed for herbal products. 


Types   Definitions  
Infusions   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   Decoctions are solutions of botanicals prepared by boiling in water for at least 15 minutes and straining. Typically, decoctions are 5% in strength. 
Tinctures   Tinctures are solutions of botanical substances in alcohol and water obtained by extracting the powdered, flaked, or sectioned botanical. 
Pulverata   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 used as a preliminary step before proceeding to granulation. Since spray-dried plant extracts usually exhibit a small particle size and poor flow, they often lead to weight variation and poor content uniformity within tablets. Using a proper granulation technique, the particle size can be increased to improve the flow rate. 

  • Direct compression 

The selection of the direct compression technique depends upon the quantity of ingredients in the formulation. It is not a feasible method for dietary supplements which contain more than one plant or mineral ingredient. Direct compression is recommended for moisture-sensitive herbal actives.     

The use of other granulation techniques, including fluid bed granulation, wet granulation, and roller compaction, depends upon the nature of the plant materials and 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 a long time may have altered active content concentration, and it needs to be accounted for when producing the final dosage form. Different extraction methods and processing steps can impact the physical and chemical properties of the final plant extract. Manufacturers must have a thorough physicochemical characterisation of the plant extracts obtained from multiple suppliers. 


Manufacturing plant-based nutraceuticals have always remained a difficult task for manufacturers. The diverse nature of the plant materials, variability in the active component quantity, and the associated microbial load make the overall manufacturing operations quite complex, demanding careful planning of the entire production process. However, the extensive knowledge of the physicochemical properties of the active ingredients can significantly relieve the manufacturers, guiding them in selecting the right granulation technique for the product and setting appropriate quality controls.  



Handbook of pharmaceutical granulation technology, Edited by Dilip Parikh, 3rd edition 


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