Binders Need and used in Solid Formulation

 

Vikranti W. Koli*, Manohar D. Kengar, Amruta B. Kamble, Suraj B. Kumbhar,

Rahul P. Jadhav

Department of Pharmaceutics, Rajarambapu College of Pharmacy, Kasegaon, Dist –Sangli, Maharashtra,

India 415404.

*Corresponding Author E-mail: vikrantikoli28@gmail.com

 

ABSTRACT:

Binders are agents employed to impart cohesiveness to the granules. This ensures the tablet remains intact after compression. The development of new excipients for potential use as binding agent in tablet formulations continues to be of interest. This is because different binding agents can be useful in achieving various tablet mechanical strength and drug release properties for different pharmaceutical purpose. Natural polysaccharides are widely used in the pharmaceutical and food industry as excipients and additives due to their low toxicity, biodegradable, availability and low cost. Natural binders like different starches, gums, mucilages dried fruits possess binding capacity as well as some other properties like disintegrants, filler, sustain release, and these natural polymers are much safer and economical than polymers like PVP. Different starches like rice, potato, maize, corn, wheat, tapioca starch and gums like ferula gummosa boiss, gum olibanum, beilschmiedia seed gum, okro gum, aegle marmelod gum, gum cordial, okra gum and cassia roxburghii seeds gum and plant fruit like date palm fruit and orange peel pectin shows good potency as a binding agent.

 

KEYWORDS: Excipients, polymer, granule, tablet.

 

 


INTRODUCTION:

In recent years, plant derived polymers have evoked tremendous interest due to their diverse pharmaceutical applications such as diluent, binder, disintegrant in tablets, thickeners in oral liquids, protective colloids in suspensions, gelling agents in gels and bases in suppository. They are also used in cosmetics, textiles, paints and paper-making[1]. Natural gums and mucilages are naturally occurring components in plants, which are essentially cheap and plentiful, are widely employed as natural excipients for conventional and novel dosage forms and show potential to be biodegradable polymeric materials.

 

With the increasing interest in polymers of natural origin, the pharmaceutical world has compliance to utilize most of them in the formulations. In recent years, there has been an incredible growth in natural products, which are essential to be used for a variety of purposes [2]. Many studies have been conducted in the fields including food technology and pharmaceuticals using gums and mucilages. The predictable use of excipients in drug formulations was to act as inert vehicles to provide the required weight, consistency and volume for the correct administration of the active ingredient, but in modern pharmaceutical dosage forms they often fulfil multi-functional roles such as modifying release, enhancement of the stability and bioavailability of the active ingredient, upgrading of patient acceptability and ensure simplicity of manufacture. A large number of plant-based pharmaceutical excipients are available today. Several researchers have explored the usefulness of plant-based materials as pharmaceutical excipients like binder, disintegrating agent, emulsifying agent etc. Capability to produce a wide range of material based on their properties and molecular weight, natural polymers became a thrust area in majority of investigations in drug delivery systems. Natural gums and mucilages can also be modified to meet the requirements of drug delivery systems and thus can compete with the synthetic excipients available in the market [3]. The aim of this article is to highlight the natural gums and mucilages as natural binding agent in various pharmaceutical dosage forms.

 

Binding agents:

Binding agent or binders are employed to convey the cohesiveness to the granules. Binders are added to the tablet formulation to impart plasticity as well as increases inter-particulate bonding strength in the tablet that ensure the tablet remains intact after compression. To hold various powders together to form a tablet, binder is added either in dry mix or mix in granulating liquid and form matrix with fillers and drug embedded in it. On drying solid binder forms glue which holds the particles together, the wet binder is the most important ingredient in the wet granulation process; most binders are hydrophilic & most times soluble in water. Different

 starches like rice, potato, maize, corn, wheat, tapioca starch and gums like ferula gummosa boiss, gum olibanum, beilschmiedia seed gum, okra gum, aegle marmelod gum, gum cordial, okra gum and cassia roxburghii seeds gum and plant fruit like date palm fruit and orangepeel pectin shows good potency as a natural binding agent. They also holds some other properties like filler, disintegrant, thickening agent and are safe and economical than synthetic polymers like PVP. A binding agents is substance that are holds others materials together mechanically or adhesive to form a cohesive whole.

 

Types of binder:

a.     Classification on the basis of their resource

 

Types of binder according to the source:

 Natural binder: Example-Methyl cellulose, Ethyl cellulose, carboxy methyl cellulose etc

a.     Animal Source: E.g. Chitin, Chitosan

b.     Marine Source: E.g. Agar, algimic acid

c.     Microbial Source: E.g. Xanthan, dextran

d.     Plant Source: E.g. Acacia, tragacanth

 


 

B Classification on the basis of their function

 

 


Advantages of natural binder:

a.       They can be used to alteration of the drug release and thereby influences the absorption and bioavailability of the integrated drugs.

b.       Natural binders are widely used in the pharmaceutical and food industry as excipients and additives due to their low toxicity, biodegradable, accessibility and low in cost.

c.        They act as vehicles which convey the integrated drug to the absorption site and precision and accuracy of the dosage, and also improve the organoleptic properties of the drugs where required in order to enhance patient faithfulness.

d.       They should conduct the performances of dosage forms during manufacturing as well as when patients consume them.

 

Disadvantages of polymer binders:

a.       Polymers binder can lead to processing problems such as rapid over granulation, tablet hardness increases & dissolution rate is decrease.

b.       In case of polymer binders, addition of strong disintegrates usually required but these are huge expensive and have a negative effect on product stability.

 

Classification of natural gum and mucilage:

Gums are present in elevated quantities in varieties of plants, animals, seaweeds, fungi and other microbial sources, where they act upon a number of structural and metabolic functions; plant sources make available the largest amounts. The different available Gums can be classified as follows:

 

According to the source:

a.     Animal source: chitosan and chitin, chondroitin, sulphat.

b.     Marine source: Agar, alginic acid, laminarin

c.     Microbial source (bacterial & fungal): Xanthan, dextran

d.     Plant source: Shrubs/tree exudates – example: gum Arabica, gum ghatti etc.

·      Seed gums – example: guar gum, locurt gum etc. 

·      Extracts – example: pectin, larch gum etc. 

·      Tuber and roots - example: potato starch etc.

 

According to the shape:

a.     Linear: Example - Amylose, cellulose, pectin

b.     Branched: Short branch – Example - Xylan, xanthan

c.     Branch on branch–Example-Amylopectin, gim arabic

 

According to the charge:

a.     Non-ionic: Example – Guar gum, xanthan gum, dextrin

b.     Anionic: Example – Alginic acid, pectin, karaya gum

c.     Cationic: Example – Chitosan, chitin, cationic guar gum

d.     Amphoteric: Example – Carboxymethyl chitosan, N-Hydroxyldicarboxyethyl chitosan

e.     Hydrophobic: Example–Cetylhydroxyethyl cellulose, polyquaternium

 

According to the monomeric units present in chemical structure

a.     Homoglycan: Example–Amylose, arabinose, cellulose

b.     Diheteroglycan: Example–Algins, carragennans, galactomannans

c.     Triheteroglycans: Example – Arabino xylans, gellan gum, xanthan gum

d.     Tetrahetero glycans: Example–Gum arabic, psyllium sed gum

e.     Pentahetero glycans: Example–Gum ghatti, gum tragacanth

 

According to the preparation

a.       Semi Synthetic:

        Starch derivative – Example: Starch acetate, starch phosphate
 Cellulose derivative–Example: Carboxymethyl cellulose, HPMC

b.       Synthetic: Example–Dextrin, scleroglucan

Advantages of natural gum and mucilage:

In comparison to the synthetic polymer, natural polymer (gum and mucilage) posses a lot of advantages and these are as follows:

 

Biodegradable:

Biodegradable polymers that are widely available in nature are produced by all living organisms. They are from recyclable sources and have no side effects on human health.

 

Local availability:

In most of the developing countries, the production of plant such as tragacanth and guar gum are promoted by the government. This is because the application of this material increases day by day in various industries.

 

Low cost:

As these are widely distributed and available in nature, the production cost is less as compare to the synthetic one.

 

Biocompatible and nontoxic:

As nearly all the gum and mucilages that are obtained from plant resources, are composed of repeating monosaccharide units and are carbohydrates. Hence they are nontoxic and biocompatible.

 

Eco-friendly processing:

As the collection of the gum taking place seasonally from different sources and ease of production procedure, hence they are ecofriendly.

 

Patient tolerance:

These produces better patient tolerance as well as public acceptance because of their production from natural source and less side effect as compare to the synthetic polymer.

 

Disadvantages of synthetic polymer:

Though the utility of synthetic polymers are increasing day by day, these shows certain disadvantages. These are as follows:

a.       The synthetic polymers are non recyclable, creates environmental pollution during synthesis, very high in cost, produces side effects and poor patient compliance.

b.       Certain processing difficulties can be created by the Polymer binder such as rapid over granulation, increase in tablet hardness and decrease in dissolution performance.

c.        Additions of strong disintegrating agent are needed with polymer binder which is very expensive and have a negative outcome on product stability.

d.       Studies in rats have shown that 5% polyvinyl alcohol aqueous solution when given in subcutaneous injection produces anaemia and can infiltrate various organs and tissues.

e.        Acute and chronic adverse effects (eye and skin irritation) have been observed in workers handling the related substances like methyl methacrylate and poly methyl methacrylate.

 

 

Some drawbacks of natural gum and mucilage’s:

Microbial contamination-The equilibrium moisture content present in the gums is normally 10% or more and, structurally, they are carbohydrates and, during production, they are exposed to the external environment and, so there is a chance of microbial contamination. However, this can be prevented by proper handling and the use of preservatives. Batch to batch variation-Synthetic manufacturing is a controlled procedure with fixed quantities of ingredients, while the production of gums is dependent on environmental and seasonal factors.

 

Examples of natural gum and mucilages are binders.

 

Natural gum and mucilage as binder:

Most of the natural polymer (gum and mucilage) are formed by high molecular weight carbohydrates. They are biodegradable, biocompatible and non-hazardous polymers showing irregular physical-chemical properties and environmentally sustainable features. Carbohydrates represent the most abundant biological molecules, covering a large array of fundamental roles in living things: from the reserve and transport of energy, (starch and glycogen), to the development of structural components (cellulose in plants, chitin in animals), to the linking between intercellular walls (hemicellulose). The high molecular weight carbohydrates derived, are known as polysaccharides.

 

Dioscorearotundata as a binding agent:

The use of Dioscorea rotundata as a binder and disintegrant in tablet formulation and Itiola also investigated the compressional properties of this particular starch [4]. The effects of pigeon pea and plantain starches on the compressional, mechanical and disintegration properties of Paracetamol tablets have been investigated. The role of ginger starch as binder in acetaminophen tablets was found.

 

Starch 1500 as a binding agent:

Starch 1500 performed as an excellent binder producing a granulation that was compressible and produced Lamivudine tablets of improved hardness and friability compared with those prepared with povidone. The formulation of Lamivudine tablets with Starch 1500 exceeded the disintegration and dissolution performance of the povidone formulation that utilized a super disintegrant [5]. The nature and amount of the binders were found to alter the disintegration and dissolution rates of the tablets by reducing their wet ability as measured by the adhesion tension of water. During pharmaceutical granulation, the objective is to produce granules that have a uniform (and repeatable) distribution of drug particles within the bulk carrier (excipient) solid [6]. This can be difficult to achieve and both drug depletion and enrichment in granules can occur [7]. A linear relationship has found to exist between adhesions of water.

 

Tapioca starch as binging agents:

The use of a natural product tapioca starch as binding agent in the formulation of Diclofenac tablets was identified. To establish two other commonly used disintegrating agents potato starch and maize starch were selected and formulated for comparison. Different formulations were prepared by using above three disintegrants in the concentration of 20 mg per tablet. The tablets were prepared by wet granulation technique. All the formulations were subjected to in in-vitro evaluation and the results were compared. The nature and amount of the binders were found to alter the disintegration and dissolution rates of the tablets by reducing their wet ability as measured by the adhesion tension of water.

 


 

Mechanism of natural binder:

 

Fig. no- 1 Mechanism of natural binder


Some common gum and mucilages and their application in pharmacy

Table no-1 some common gum and mucilages and their application in pharmacy

Gum and Mucilage

Botanical Source

Family

Application in Pharmacy

Reference

Almond gum

Prunus communis

Rosaceae

Suspending agent Thickening agent Stabilizer

[8]

Gum moringa

Moringa olifera

Moringaceae

Disintegrating agent

[9]

Okra mucilage

Abelmoschus esculentus

Malvaceae

Suspending agent Disintegrating agent

[10, 11, 12]

Aegle gum

Aegle marmelos

Rutaceae

Binder Thickening agent

[13]

Gum acacia

Acacia catechu

Leguminosae

Suspending agent Antioxidant Astringent

[14]

Tamarind gum

Tamarindus indica

Fabaceae

Gelling agent, Stabilizer, Binder

[15]

Prunus gum

Prunus domestica

Rosaceae

Binder, tonic

16]

Gum ferula

Ferula gummosa

Apiaceae

Binder

[17]

Cassia roxburghii mucilage

Cassia roxburghii

Fabaceae

Binder Thickening agent

([8, 19]

Fenugreek mucilage

Trigonella foenum-graenum

Leguminosae

Solubulizing agent Binder

[20]

Brachystegia mucillage

Brachystegia eurycoma

Leguminosae-caesalpinioideae

Emulsifying agent Stabilizer Thickening agent

[21]

Ayoyo gum

Cochorus olitorius

Tiliaceae

Emulsifying agent Thickening agent Binder

[22]

Gum kondagogu

Cochlospermum gossypium

Bixaceae

Thickening agent Emulsifying agent

[23]

Cordia gum

Cordia obliqua

Boraginaecae

Binder Stabilizer

[24]

Gum odina

Odina wodier

Anacardiaceae

Binder Stabilizer

[25]

Cassia tora mucilage

Cassia tora

Caesalpiniaceae

Binder Disintegrating agent

[26]

Cassia fistula

Cassia fistula

Caesalpiniaceae

Granulating agent Binder

[27]

 


CONCLUSION:

There are great numbers of natural substances have been used in pharmaceutical preparations. Natural substances like gums, mucilage’s, and also dried fruits can be used as binding agent. They have been shown good potential as binding agent as well as they hold some other properties like fillers, disintegrating agent, sustain releasing agent. Natural gums and mucilages exposed good binding property in wet granulation for the manufacturing of tablets; granules are stable and less friable in contrast with other binders. Natural binders are non-polluting renewable resources for sustainable supply of cheaper pharmaceutical excipients or product. They are also act as vehicle which transports the incorporated drug to the site of the absorption and stability of incorporated drug to the site of absorption.

 

ACKNOWLEDGEMENT:

Authors are highly Acknowledge the help of teaching staff of Rajarambapu College of Pharmacy, Kasegaon. For providing necessary information required for research work. Also we are highly Acknowledge the help and guidance of Dr. Mangesh A. Bhutkar.

 

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Received on 02.03.2019          Accepted on 10.04.2019         

© Asian Pharma Press All Right Reserved

Asian J. Pharm. Tech.  2019; 9(2):129-134.

DOI: 10.5958/2231-5713.2019.00022.9