Tablet binders or binding agents are substances that are added in a formulation to form granules either in dry or liquid form during wet granulation or in dry form during dry granulation or directly compressed tablets[1]. Examples of tablet binders or binding agents are starch, pregelatinized starch, PEG, sorbitol, and HPMC, etc.
Tablet Binders and disintegrants have the opposite use in an oral solid formulation. Binding agents delay tablet disintegration while disintegrant increases tablet disintegration. Do you know the name of disintegrants used in pharmaceutical preparations? So, the proper amount of tablet binders is required for a proper formulation. They play a vital role in making sure pellets or granules and tablets remain in shape until they reach their target by holding all ingredients (API and Excipients) together in any solid dosage form. Selecting the correct binder is critical to maintaining the integrity of the tablet. Which is the desired release profile (immediate or modified) a formulator must know before choosing a binder?
Table of Contents
Classification of Tablet Binders
Based on their source:
- Natural: These are less toxic, biodegradable, availability at low cost. Examples include starch, pregelatinized starch, Sodium alginate, and gelatin, etc.
- Synthetic/ Semisynthetic: These are the most widely used and required a low amount in a formulation. Examples include Polyvinyl Pyrrolidone (PVP), Methylcellulose, Hydroxy Propyl Methyl Cellulose (HPMC), Polymethacrylates, Sodium Carboxy Methyl Cellulose, Polyethylene Glycol (PEG) and Methylcellulose, etc.
- Saccharides and their derivatives: Disaccharides such as lactose and sucrose; Polysaccharides and their derivatives such as starches, cellulose, or modified cellulose such as MCC and cellulose ethers such as hydroxypropyl cellulose (HPC); Sugar derivatives such as sorbitol, xylitol, and mannitol, etc.
Image of Carboxymethyl Cellulose
Based on their application in the manufacturing process:
- Dry tablet binders: These are added to the powder blend, either after a wet granulation step or as part of a direct compression (DC) formula. Examples of Dry tablet binders include cellulose, Polyvinyl Pyrrolidone (PVP), Hydroxy Propyl Methyl Cellulose (HPMC), Sodium CarboxyMethyl Cellulose, Polyethylene Glycol (PEG), and Methyl Cellulose.
2. Solution tablet binders: These are used in wet granulation processes. These are dissolved in a different solvent such as water or isopropyl alcohol. Examples of Solution tablet binders include cellulose, gelatin, cellulose derivatives, polyvinyl pyrrolidone, starch, sucrose, mannitol, polyethylene glycol, and liquid glucose, etc.
Why Tablet Binders is necessary for Granulation?
During compression fine particles of power, (both active and inactive ingredients) or granules must have two properties:
Firstly, Proper Flow property: Fine particles have fewer flow properties and thus, they make problems such as weight variation, and segregation of powder particles during manufacturing.
Secondly, Proper Compressibility: Particles of powder or granules of the tablet should have proper compressibility. Compressibility is required for the proper compression of tablets.
Binding agents can accumulate fine particles to large particles (granules) and these large particles have adequate flow properties and compressibility. Certainly, during compression particles need to compact and this is possible when one or more binders are used in a formulation. Thus, tablet binders are added either in dry or liquid form during wet granulation to form granules or to promote cohesive compacts during dry granulation or directly compressed tablets. In addition, the binder ensures the tablet shape remains unbroken after compression.
List of Tablet Binders Used in Pharmaceutical Preparations [2]
| Name of Tablet Binders | Concentration (%) |
| Acacia | 1.0 – 5.0 |
| Calcium carboxymethylcellulose; calcium cellulose glycolate; carmellose calcium; | 2.0 – 5.0 (In direct compression) 2.0 – 5.0 (In wet granulation) |
| Carbomer | 0.75 – 3.0 |
| Corn Starch and Pregelatinized Starch | Commercially known as STARCH 1500 |
| Calcium carboxymethylcellulose; calcium cellulose glycolate; Carmellose calcium; | 5.0–15.0 |
| Carboxymethylcellulose Sodium, Carmellose Sodium | 1.0–6.0 |
| Ceratonia | 0.15 – 0.75 [3] |
| Chitosan Hydrochloride | Chitosan is a well-known polysaccharide |
| Dextrates | Ethylcellulose is blended dry or wet granulated with a solvent such as ethanol (95%). |
| Dextrin | Low-molecular-weight carbohydrates |
| Ethylcellulose | Hydroxyethyl methyl Cellulose |
| Liquid Glucose | 5.0 – 10.0 |
| Guar Galactomannan,/ Guar Gum | Up to 10.0 |
| Hydroxyethyl Cellulose | Derived from cellulose |
| Hydroxyethylmethyl Cellulose | Derived from cellulose |
| Hydroxypropyl Cellulose | 2.0 – 6.0 |
| Low-Substituted Hydroxypropyl Cellulose | Most widely used |
| Hydroxypropyl Starch | modified starch |
| Pregelatinized Starch | Concentrations between 2% and 5% w/w may be used as a binder |
| Inulin | Naturally occurring polysaccharides |
| Magnesium Aluminum Silicate | 2.0 – 10.0 |
| Maltodextrin | 2–40 (direct compression) 3–10 (wet granulation) |
| Methylcellulose | 1.0–5.0 |
| PEG (Polyethylene Glycol) | Depending on MW (molecular weight) of PEG, it is also known as polyethylene oxide (PEO) or polyoxyethylene (POE). |
| Polyethylene Oxide | 5.0 – 85.0 |
| Povidone | 0.5 – 5.0 |
| Sodium Alginate | 1.0 – 3.0 |
| Starch | 3–20% w/w (usually 5–10%, depending on the starch type) as a binder for wet granulation |
| 5–20 as a dry binder in tablet formulations | 5-10% w/w |
| Sucrose | 2–20 (Dry granulation) 50–67 (Wet granulation) |
| Compressible Sugar | 10–35 Dry mix [4] 15–35 as a solution (4.5–10.5% w/w solids) |
| Zein | 30 (Wet granulation) |
| Gelatin | 1–3 Wet mix [4] |
| Polymethacrylates | Sodium Alginate |
| Sorbitol | 2–10 Wet mix [4] |
| Glucose | 2–25 Wet mix [4] |
| Sodium alginate | 1–3 Wet mix |
Ideal properties of tablet binding agents
- Physiologically inert.
- Acceptable to regulatory agencies.
- Physiologically and chemically stable.
- Should not interfere with the bioavailability of the drug.
- Commercially available in a stable form.
- Meet the standards of regulatory requirements.
- Able to cohesive compacts for directly compressed tablets.
We know that the tablet is one of the most used and preferred dosage forms. Tablets are formed by using either
- Direct Compression
- Dry Granulation
- Wet Granulation
However, tablet binders are one of the most essential excipients for tablet manufacturing. They are used in the formulation of solid oral dosage forms to hold the API (active pharmaceutical ingredient) and excipients (inactive ingredients) together and to promote cohesive compacts for directly compressed tablets.
Also, You may read:
- Problems in Tablet Manufacturing.
- What are disintegrating agents or disintegrators or disintegrants?
- List of Sweetening agents used in Pharmaceutical Preparations.
References
- Lachman, Lieberman, H.A. and Kanig, J.L., The Theory and Practice of Industrial Pharmacy, Lea and Febiger, New York, 15th edition., 2013.
- Rowe, R. C., Sheskey, P. J., Owen, S. C., & American Pharmacists Association. (2006). Handbook of pharmaceutical excipients. London: Pharmaceutical Press.
- Gaud, R. S. (2008). Natural excipients. Pune, India: Nirali Prakashan.
- Cantor, Stu & Augsburger, Larry & Hoag, Stephen & Gerhardt, Armin. (2008). Pharmaceutical Granulation Processes, Mechanism and the Use of Binders.