INTRODUCTION:

A substance that is employed to deliver a medication, i.e., with just the purpose of serving as an inert carrier for the active ingredients, is referred to as an excipient¹. The Latin word excipients, which means to receive, together, to the out, is the origin of the English word excipient. The production procedures, active pharmaceutical ingredients (API), and excipients employed in the formulation all affect the product's quality. These excipients significantly contribute to the performance of the API, supporting the product's safety and efficacy.² Excipients are typically utilised in conventional dosage forms such tablets and capsules as diluents, binders, disintegrants, adhesives, glidants, and sweeteners³.

The pharmaceutical industry uses a number of plant-derived pharmaceutical excipients as binding agents, disintegrants, sustaining agents, protective, colloids, thickening agents, gelling agents, bases in suppositories, stabilisers, and coating materials⁴. Starch, agar, alginates, carrageenan, guar gum, xanthan gum, gelatin, pectin, acacia, and tragacanth are some of the excipients in these products. Herbal excipients are affordable, non-toxic, and biodegradable (with some exceptions) because they are natural. Customers are drawn to products that are biocompatible, environmentally safe, and can be chemically altered. Plant resources can offer a consistent supply of raw materials because they are renewable and can be grown or harvested in a sustainable manner. Waste from the food industry could be used as a raw material to extract herbal excipient. As excipients for plant-derived polymers, herbal materials are increasingly in demand for the following reasons: The diverse uses of plant-based polymers in medications as diluents, binders, thickeners, suspending agents, and other components have resulted in a considerable surge in research on the textile and paper sectors⁵. Excipients are now understood to have the capacity to affect a drug's rate and/or amount of absorption, contrary to the long-held belief that they are inert and have no therapeutic or biological effects or alter the biological activity of the pharmacological ingredient. Herbal excipients play a significant part in pharmaceutical formulation because they are non-toxic and compatible. As a result, this article provides a summary of natural excipients that are utilised in both traditional and cutting-edge drug delivery methods⁶. Because they are renewable and can be grown or harvested sustainably, plant resources can provide a steady supply of raw materials. Herbal excipients can be extracted from waste products from the food industry as a starting point. For the reasons listed above and others, there is an increasing demand for herbal materials as excipients⁷.

CLASSIFICATION OF HERBAL EXCIPIENTS:

Excipients are frequently categorised in accordance with how they are used and perform in pharmaceutical products:

· Diluents and binders

· Polishing

· Lubricants, gliders, and disintegrants,

· Film makers and coatings professionals

· Suspending agents, colorings, and plasticizers

· Antioxidants, flavourings, sweeteners, and taste-improving ingredients

· Inks for printing, Dispersing agents, Gums⁵

Binder:

Acacia

In order to provide the finished product more mechanical strength, binder excipients are intended to act as an adhesive, binding powders, granules, and other dry materials together. Binders are used to create granule formulations that are more effective and predictable. They can also add volume to low active dosage tablets, which are frequently used in wet granulation. For instance, solution binders are categorised based on their use and are dissolved in a solvent like gelatin cellulose derivatives. To polyvinyl pyrrolidone starch, sucrose and polyethylene glycol are added.⁸

Examples of natural binders – Acacia, Alginic acid, Corn starch etc

Diluents:

Starch

A diluent is a diluting agent (also known as a filler, diluent, or thinner). Some liquids are either too thick to flow from one place to another or too viscous to be easily pumped. This can be problematic since it might not be profitable to transfer these fluids in this form. To help with the restricted mobility, diluents are utilised. This lowers the cost of pumping and transporting as well as the viscosity of the fluids.⁹

Examples of some natural diluents : Starch, cellulose, Lactose, mannitol etc.

Fillers:

To make the material larger and easier to process so that it can be produced into a size that is suitable for eating, filler excipients are utilised. They can assist in manufacturing and product stabilisation as well. In several dosage forms, such as tablets, pills, pellets, paste, solutions, suspensions, and emulsions, filler and diluent are employed. 10

Examples of natural fillers are – Plant cellulose, Gelatin, Lactose, Sucrose, Glucose etc

Lubricant:

Aloe Vera

Excipients called lubricants are used to lubricate processes, which involves adding substances to make them operate more smoothly. In the manufacturing process, lubricants are utilised to prevent the clumping of components used in formulations. Lubricants keep the formulation sticky and lessen friction between particles and machinery used for processing. Similar to solid dosage forms, lubricants are incorporated into formulations in very small amounts. Tablets, capsules, pills, pastes, suppositories, pellets, and other dosage forms are examples of dosage forms in which lubricants are used.¹¹

Examples of some natural Lubricant : Aloe vera, Castor oil, Mineral oil, Paraffin oil etc

Glidants:

Tragacanth

To enhance the flow of the tablet-core mix material, glideants are used into the formulation. During the initial phases of compression, glideants are added to the particle configuration of the tablet powder mix to improve flow and homogeneity inside the die cavity of tablet presses. Talc has a concentration restriction because of its retardant influence on the dissolution-disintegration profile, despite the fact that it is regarded to be a better glidant than starch. Glidants make it easier for tablet granulation to flow by reducing friction between particles.¹²

Examples of some natural glidants are : Tragacanth,

Disintigrants:

Agar

To aid in de-aggregation, disintegrants are added to oral solid dose forms. Disintegrants are substances that are intended to swiftly dissolve solid dosage forms when they come into contact with moisture.¹³

Example of some natural disintigrants : Agar, chitosan, microcrystalline cellulose, Guar gum, silicon etc.

Polishing film formers:

Paints contain film formers, which are employed as a surface application on steel surfaces. They function as corrosion inhibitors and are inexpensive chemical agents that aim to preserve steel's immaculate appearance. Film formers also shield the steel surface from contaminants like rust and corrosion.¹⁴

Coating agents:

Beeswax

Coating agents are equally useful in individuals as they are in pharmaceutical solid dosage forms. To coat or create a film, coating agents are added to the dosage form. These coating techniques alter medication release while enhancing drug protection. Depending on the precise site of drug release, coating agents are used to prevent the stomach from being affected and to absorb the medication from the intestines. Coating agents increase a formulation's attractiveness.^{15, 16}

Typical dose forms for coating agents include: pills, capsules, tablets, etc.

Examples of some natural coating agents : Gelatine, beeswax, parrafin wax, shellac etc

Plastisizers:

Plasticizers are chemicals added to materials to soften and make them more flexible; some are better at this than others¹⁷. Ester and petroleum oils are the two categories of plasticizers for elastomers. In general, polar elastomers gain from ester plasticizers while nonpolar elastomers benefit from petroleum oils when it comes to processing.¹⁸ Ester and petroleum oils are the two categories of plasticizers for elastomers. In general, polar elastomers gain from ester plasticizers while nonpolar elastomers benefit from petroleum oils when it comes to processing.¹⁹

Coloring agents:

Annato

Examples of dose forms that contain colouring agents: Tablets, pills, pallets, capsules, pastes, ointments, syrups, emulsions, and suspensions, among other things.

Examples of some natural coloring agents are : Annatto, Carotene, Chlorophyll, cochineal, Curcumin

Classification:

Natural dyes made from plant materials including berries, flowers, bark, leaves, seeds, and so on are categorised as:

• Natural hues originating from insects, such as cochineal and lac

• Mineral-based natural colours including clay, ochre, and malachite;

• Animal-derived natural dyes like mollusk, murex snail, cuttlefish, and shellfish.²⁰

Suspending agents:

Gum acacia

The most often used suspending agents are aqueous biological polymers like methylcellulose (MC), sodium carboxymethylcellulose (CMC), and hydroxypropylmethylcellulose (HPMC). There are many different viscosities and molecular weights of suspending agents.²¹

There are so many herbal suspending agents in nature.

Example : Alginates, acacia gum, tragacanth, guar gum, bean gum, carrageenan, xanthan gum, microcrystalline cellulose, powdered cellulose)

Preservatives :-

Vinegar

Chemical substances known as preservatives can be found in the food, cosmetics, and pharmaceutical industries. They are incorporated into formulation to prevent microbial growth from causing product degradation. Additionally, they stop the harmful chemical changes from happening. The two types of preservatives that are most frequently utilised are anti-oxidants and antimicrobial preservatives.²²

Natural preservatives are obtained by herbal plants.

Examples : Vinegar, rosemary extract, neem oil, citrus oils, citric acid, grapeseed

Antioxidants:

Beetroot

A substrate known as an antioxidant prevents molecules within a cell from oxidising. It is a well-known chemical process that enables the removal of electrons or hydrogen from a substance. Antioxidants are frequently used as food supplements, and researchers have looked into how well they help shield against illnesses like cancer and heart disease. Examples of flavouring agents include sweeteners, flavour enhancers, and flavouring agents.²³

Some herbal plants are used as antioxidant property

Example : Beetroot, Broccoli, spinach, carrots and potatoes

Flavoring agents:

Peppermint

Combining the senses of touch, taste, smell, and sight creates flavours. Today, the artificial flavouring sector uses technology to create a wide variety of flavours. Medicinal products like cough syrups, sedatives, antimalarials, and antibiotics all contain flavours. The food business frequently uses flavours as well. Organoleptic agents include flavouring substances. To cover up an unpleasant taste or dose form order, flavours are used as taste masking agents.²⁴

Natural flavoring agents are obtained by herbal plants.

Some flavouring agents extracted from herbal plant.

Example : Peppermint, Ginger, rose, lemon, clove, strawberry, raspberry, orange, etc.

Sweeteners:

Honey

Food additives known as sweeteners are said to be used or intended to be used as tabletop sweeteners or to give meals a sweet flavour. Tabletop sweeteners, which are often used as a sugar alternative, are sweeteners that are composed of or comprise any of the approved sweeteners and are intended for sale to the final consumer. Sugar and honey, which are used to sweeten food, are not additives and are therefore exempt from regulatory regulations. Sweeteners are split into two groups: bulk and high intensity.²⁵

There are so many natural sweetners are available in nature, they are obtain by plant sources

Examples : Honey, dates, Stevia,etc.

Taste improving agent:

Stevia

Monosodium glutamate (MSG), sodium chloride (NaCl), and sweeteners are just a few examples of dietary ingredients that have been given the name "taste enhancers," yet their main effect is to simply add additional molecules that generate greater taste or smell sensations. For instance, MSG, salt, and sweeteners just add to the meaty/savory, salty, or sweet qualities of other chemosensory features rather than actually enhancing them.²⁶

Some natural taste improving agents are :

Example : Stevia, Honey, liquorice, serendipity berry, thaumatin,etc

Printing inks:

Lavender

Printing inks are put to the surface in a very thin layer, as opposed to paints and varnish coats, with a thickness that can range from 2 to 30 m, depending on the printing method. Liquid substances called inks are used for writing and printing. Their main function is to stain a surface and leave behind a pattern, picture, or text²⁷.

Natural inks are made up of plant pigments .

Example : Red/Pink ink – Crush rose, lavender, and hibiscus.

Blue ink – Hyacinth flowers.

Green ink – Lily of the valley.

Yellow ink – Marigolds, daffodils, buddleia and dandelions.

Orange ink - Dyer's Coreopsis.

Purple ink - Red peonies

Dispersing agents :-

Castor oil

The dispersion agents for coatings and ink formulations include solutions for aqueous, solvent-based, high solids, 100% solids, and universal pigment concentrates. These surfactant-based, polymeric, and oligomeric technologies are renowned for their adaptability to low-VOC and APEO-free systems as well as their superior colour development, viscosity reduction, increased gloss, and durability.²⁸

Some examples of dispersing agents –

Castor oil

Gums :-

Gum Acacia

Gums are amorphous, translucent substances that are made by plants. Gums are typically pathological byproducts that arise when a plant is injured or growing in unfavourable conditions. Anionic or nonionic polysaccharides called gums are present in plants. When gums are hydrolyzed, sugar and salts of uronic acid are produced.²⁹

Examples of natural gums :

gum Arabic (Acacia senegal), gum ghatti, (Anogeissus latifolia), neem gum (Azadirachta indica), gum karaya (Sterculia urens; Cochlospermum gossypium), Joel or Jingan gum (Lannea coromandelica), and Mesquite gum (Prosopis juliflora)

ADVANTAGES OF HERBAL EXCIPIENTS:

· Biodegradable: All living things produce polymers that occur spontaneously. They don't have any detrimental effects on people or the environment.

· Biocompatible and non-toxic: These plant ingredients are almost all carbohydrates, which are repeating monosaccharide units in nature. They are therefore not poisonous.

· Economical: Compared to synthetic materials, they are less expensive to produce.

· Safe and without side effects: Because they come from a natural source, they are risk-free and without negative consequences.

· Easy accessibility: They are produced in numerous nations as a result of their widespread use in a variety of industries³¹.

DISADVANTAGES OF HERBAL EXCIPIENTS:

· Microbial contamination - Because they are exposed to the environment outside while being produced, this is a potential risk.

· Variation - Unlike natural polymer manufacture, which depends on the environment and a number of physical parameters, synthetic manufacturing is a regulated process with fixed constituent quantities.

· The unregulated rate of hydration – The proportion of chemical elements present in a specific substance may vary depending on when the natural materials were collected, the species, the locality, and the climate.

· Slow Process: Since the environment and a host of other elements influence the manufacturing pace, it is unchangeable. So the rate of construction of natural polymers is slow.

· Heavy metal contamination: Herbal excipients are frequently linked to heavy metal contamination.^32,33.

APPLICATIONS OF HERBAL EXCIPIENTS:

Tamarind Gum:

A member of the 21 perennial families is the tamarind tree, Tamarindus indica. Tamarind xyloglucanis, commonly known as tamarind kernel powder (TKP), is obtained from the endosperm of the seed of the tamarind. The size range of the produced microspheres was 230-460 m. Another study looked into Diclofenac sodium matrix tablets that contained TSP. The drug release characteristics of the tablets made using the wet granulation process were assessed^34,35.

Guar gum:

The endosperm of the nut of the legume plant Cyamopsis tetragonolobus is where guar gum is derived from. When the thin layer of fibrous material that makes up the husk is cut off and separated from the endosperm halves by polishing, refined guar splits are obtained. Alkalies in high concentrations also have a tendency to reduce viscosity since they both prefer to hydrolyze substances and disregard viscosity. Most hydrocarbon solvents cannot dissolve it³⁶.

Locust bean gum:

Carob gum, also referred to as locust bean gum (LBG), is made from the refined endosperm of seeds from the Ceretonia siliqua L. carob tree. It is a tree in the family of legumes that is evergreen. The endosperm from carob tree seeds must be separated and processed in order to produce carob bean gum³⁷.

Honey locust gum:

It is known botanically as Gleditsia triacanthos and is a member of the Leguminosea family (suborder Mimoseae) The gum is acquired from the seeds^38,39.

Khaya gum:

Khaya gum is a polysaccharide obtained from the tree Khaya grandifoliola's incised trunk (family Meliaceae). The gum's availability in nature, low cost, and lack of toxicity have further stoked interest in growing it for therapeutic purposes. In the formulation of 61 controlled release tablets, additional research has also demonstrated its potential as a directly compressible matrix system⁴⁰.

Aloe mucilage:

Aloe barbadensis Miller leaves are used. In addition to the various carbohydrates, the aloe parenchyma tissue or pulp has been discovered to contain proteins, lipids, amino acids, vitamins, enzymes, inorganic chemicals, and tiny organic molecules. Numerous researchers have determined that pectic material is the major polysaccharide of the gel, along with partly acetylated mannan (also known as acemannan)⁴¹.

Hakea Gum:

Exudates from the Proteaceae family's dried Hakea gibbosa plant. Arabicagalactans are found in acidic gums (type A). Molar percentages (%) of sugar's component parts The proportions of glucuronic acid, galactose, arabinose, mannose, and xylose are 12:43:32:5:8.⁴².

Pectin:

Pectins are linear polysaccharides that aren't starches that are taken out of plant cell walls⁴³. To increase the stability of folic acid in food preparation, microcapsules containing the vitamin were created using alginate and combinations of alginate and pectin polymers. In comparison to capsules made with alginate alone, those with an integrated alginate and pectin polymer matrix increased the folic acid encapsulation efficiency and reduced leakage from the capsules. They also demonstrated higher folic acid retention after freeze drying and storage⁴⁴.

Alginates:

Alginates are naturally occurring polysaccharide polymers that were extracted from brown seaweed (Phaeophyceae). Alginate can be transformed into its salts, of which sodium alginate is the most widely utilised type right now. Alginates have a wide range of uses in drug administration, including the transfer of biomolecules in tissue engineering applications, matrix type alginate gel beads, liposomes, and modifying gastrointestinal transit time⁴⁵.

CONCLUSION:

The development of natural excipients is receiving a lot of attention at the moment. Polymers are essential for the delivery of drugs. Therefore, choosing the right polymer is crucial in the production of pharmaceuticals. Carrageenan, alginate, konjac glucomannan, gum arabic, guar gum, and locust bean gum are a few examples of plant-derived polysaccharides that have demonstrated excellent potential as carrier materials in matrix-type controlled release dosage forms like microparticles, beads, tablets, and cross-linked hydrogels. Before being utilised in approved dosage forms, excipients that have never been used before must undergo strict regulatory standards.

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Received on 24.01.2023 Modified on 21.02.2023

Res. J. Pharmacognosy and Phytochem. 2023; 15(2):118-124.

DOI: 10.52711/0975-4385.2023.00018