Pharmaceutical formulation is a blend of art and science. It precisely balances ingredients, processes, and techniques to create effective, safe, and stable medicines. Binders are an essential component of Oral Solid Dosage formulations. They act as cohesive agents, helping to convert individual particles into cohesive granules. Binders play a crucial role in the formation of granules, leading to control over the compression process of tablet manufacturing or filling the granules in capsules. They also directly impact the physical attributes of tablets, such as friability, chipping and important quality factors, such as hardness, disintegration time, and drug dissolution rate.

Selecting the suitable binder for wet granulation involves considering several critical criteria:

  • Solubility:The binder should be soluble or dispersible in the granulation solvent to ensure uniform distribution and effective binding.
  • Compatibility:The binder must be compatible with other formulation ingredients, including active pharmaceutical ingredients (APIs) and excipients, to prevent interactions that could affect stability or performance.
  • Granule Properties:The binder should contribute to the desired granule characteristics, such as size, strength, and flowability, to facilitate downstream processing steps.
  • Binder Concentration:Optimise the binder concentration to achieve the desired granule properties without causing issues like excessive stickiness or poor flow.
  • Processability:The binder should be easy to handle and process during wet granulation, drying, and subsequent manufacturing steps, ensuring efficient granulation and reproducible production.
  • Adhesion Properties:Select a binder with good adhesive properties to ensure proper binding of granules without excessive moisture or binder concentration.
  • Cost-effectiveness:While considering the cost of the binder, always keep in mind the ultimate goal-to ensure that it offers the desired performance at a reasonable price, contributing to the overall formulation economics.
  • Safety and Regulatory Compliance:Ensure that the binder complies with regulatory standards for pharmaceutical use and does not introduce toxic or harmful substances into the formulation.

Selection of the Right Solvent System:

Pharmaceutical granulation binders are commonly dissolved or dispersed in solvent systems like water, alcohol-water mixtures, or organic solvents like acetone. Co-solvents like glycols or surfactants may enhance solubility. Selection depends on binder properties, process requirements, and safety concerns, with water being the most common choice due to its availability and environmental friendliness.

 Commonly used binders in wet granulation

Binders% used in the formulationSolvent System
Natural polymers
Pregelatinized starch2-10Water
Alginic acid1–5Water
Sodium alginate1–3Water
Synthetic polymers
PVP0.5–10Water or isopropyl alcohol or Hydro-alcoholic
Methyl cellulose1-10Water
HPMC2-10Water or isopropyl alcohol or Hydro-alcoholic
Sodium Carboxymethylcellulose1-10Water
Ethyl cellulose1-10Ethanol
Hydroxy propyl cellulose2-5Water or isopropyl alcohol


Sugars are commonly used as binders due to their adhesive properties and solubility in water.

Glucose: Glucose, when utilised in wet-granulation processes as a syrup, exhibits favourable bonding properties. It yields granules and tablets of moderate strength, characterised by hardness and brittleness. Glucose serves as both a diluent and binder in the direct compression process.

Sucrose: Sucrose syrup serves as a binder in wet-granulation processes and is commercially available in various forms, including granular, fine granular, and superfine powder. It can also be employed as a dry binder, granulated with water or hydroalcoholic solutions. Sucrose yields robust and brittle tablets, with tablet hardness being regulated by the binder’s quantity in the formulation. Softer granules can be achieved using hydroalcoholic mixtures. Tablets containing large amounts of sucrose may experience hardening over time, potentially resulting in slower disintegration and dissolution rates.

Sorbitol: Sorbitol, renowned for its high hygroscopicity at a relative humidity of 65%, primarily serves as a humectant in pharmaceutical formulations, effectively controlling moisture levels. Its capacity to absorb and retain moisture makes it an ideal choice for formulations where moisture control is crucial. Furthermore, Sorbitol can also be harnessed as a binder in pharmaceutical granulation processes, capitalising on its inherent ability to promote cohesion among granule particles. By leveraging Sorbitol’s dual functionality as both a humectant and a binder, formulators can enhance the stability and manufacturability of pharmaceutical products while ensuring optimal performance and shelf-life.

Natural Polymers

Natural polymers are derived from natural sources such as plants, animals, or microorganisms. They offer various advantages, such as biocompatibility and biodegradability.

 Starch: Starch, a polymeric carbohydrate recognised as Generally Recognised As Safe (GRAS), is a binder in tablet formulations. It is insoluble in cold water and alcohol but forms a translucent paste when mixed with hot water. Tablet granulations with freshly prepared starch paste (5-25% w/w) yield relatively soft and friable granules, leading to tablets that readily disintegrate upon administration.

Pregelatinised Starch: Pregelatinised, modified starch functions as a binder, diluent, and disintegrant in tablet formulations. Soluble in warm water without boiling, it can be used as a solution or dry mixing followed by wetting with water. Partially pregelatinised starch, containing 10-20% cold-water-soluble fraction, acts as a binder, facilitating tablet disintegration.

Gelatin: Gelatin, derived from animal collagens through hydrolysis, is insoluble in cold water and alcohol but forms a gel in hot water, requiring warm use to avoid gel formation. Although rarely used as a tablet binder due to its tendency to produce hard tablets with slow disintegration, its properties are advantageous in lozenge formulations for a smooth mouthfeel.

Acacia: Acacia, a natural gum obtained from acacia trees, is available in powdered, granular, or spray-dried forms. Used as a binder in aqueous solution or added in dried form before moistening with water, it yields very hard tablets with slow disintegration, limiting its use in granulation.

Alginic Acid: Alginic acid, extracted from seaweed, serves as a binder at 1–5% concentrations. It gradually hydrolyses at room temperature and is best incorporated in a dry state. Incompatibility with strong oxidising agents and forming insoluble alginates with alkaline earth metals may delay tablet disintegration due to their gelling properties.

Sodium Alginate: Sodium alginate dissolves slowly in water to form a viscous solution. It is commonly utilised at concentrations of 3-5% in wet granulation processes. It also finds application in sustained-release formulations, delaying drug release from tablets.

Synthetic Polymers

Synthetic polymers are chemically synthesised compounds that exhibit specific properties suitable for pharmaceutical applications. They offer precise control over characteristics such as solubility, viscosity, and mechanical strength.

Polyvinylpyrrolidone (Povidone): Polyvinylpyrrolidone (PVP) stands as one of the most commonly used binders, readily soluble in water and alcohol. Typically utilised in solution form, it can also be added in a dry state and granulated with a solvent. Concentrations ranging from 0.5% to 5% serve as effective binders, with low to medium viscosity grades preferred to prevent dissolution issues. PVP’s high hygroscopicity necessitates careful handling to prevent moisture absorption and deliquescence.

Methyl Cellulose: Methyl Cellulose (MC) offers versatility through its various grades, with binding strength depending on the degree of substitution and molecular weight. It is practically insoluble in hot water, ethanol, and other solvents, swelling and dispersing slowly in cold water. Generally added as a dry powder or solution, it yields robust tablets with moderate hardness, which remains stable over time.

Hydroxypropyl Methyl Cellulose (Hypromellose): Hydroxypropyl methyl cellulose (HPMC) provides similar binding properties to MC and is soluble in cold water, forming a viscous solution. It is commonly utilised in concentrations of 2–5% in wet or dry granulation processes, albeit incompatible with certain oxidising agents.

Sodium Carboxymethyl Cellulose: Sodium carboxymethyl cellulose (Na-CMC) offers a variety of viscosity grades, dispersing easily in water to form a colloidal solution. Used in concentrations of 5-15%, it produces softer granules with good compressibility, though tablets may harden with age due to their high hygroscopicity.

Ethyl Cellulose: Ethyl cellulose, available in various grades, is used as a binder in concentrations of 2-10% in ethanol. It produces softer granules with good compressibility, which is ideal for water-sensitive formulations, although it may result in slower drug release due to insolubility in water.

Polymethacrylates (Eudragit): Polymethacrylates, such as Eudragit NE 30D and Eudragit RS 30D, are synthetic polymers widely used in pharmaceutical formulations. They are available as 30% aqueous dispersions and are often employed as binders in both aqueous and non-aqueous wet-granulation processes. These polymers offer excellent film-forming properties and can contribute to the controlled release of active pharmaceutical ingredients (APIs) in tablets. Eudragit polymers are pH-sensitive, allowing for targeted drug release in specific gastrointestinal tract regions. Additionally, they provide enhanced stability and protection for moisture-sensitive or light-sensitive APIs.

Polyvinyl Alcohol (PVA): Polyvinyl alcohol (PVA) is a water-soluble polymer frequently utilised in pharmaceutical formulations. It is available in various viscosity grades, ranging from 10 to 100 cps, making it suitable for a wide range of tablet granulations. PVA offers excellent adhesive properties, promoting cohesion among granule particles and facilitating the formation of robust tablets. Moreover, tablets formulated with PVA as a binder typically exhibit resistance to hardening over time, ensuring consistent performance and dissolution characteristics throughout their shelf life. Additionally, PVA can serve as a film-forming agent in coating formulations, providing a protective barrier for tablets and enhancing their stability. Overall, PVA is valued for its versatility, biocompatibility, and effectiveness in pharmaceutical applications.

Hydroxypropyl Cellulose (HPC): Hydroxypropyl cellulose (HPC) is a versatile binder used in pharmaceutical formulations, soluble in both water and organic solvents. Concentrations typically range from 2% to 5%, providing effective binding properties. HPC can be used in both wet and dry granulation processes and is known for forming strong, flexible films, which can enhance the mechanical strength of tablets. Additionally, HPC’s thermoplastic properties make it suitable for hot melt extrusion processes, broadening its application in drug delivery systems. Its high solubility and low viscosity grades help prevent issues with dissolution, making it a preferred choice for many formulations. 

Solvent-Compatible Equipment

When handling alcoholic solvents in granulation processes, special considerations are necessary to ensure safety, efficiency, and product quality.

Here are some key features and considerations for specialised granulation equipment for handling alcoholic solvents:

Explosion-Proof Design: Alcoholic solvents, such as ethanol, methanol, and isopropanol, are highly flammable and require equipment with explosion-proof features. This includes explosion-proof motors, switches, and electrical components to prevent ignition sources.

Closed-Loop Systems: Closed-loop systems, such as closed-bowl granulators or closed-drum coaters, are essential for containing alcoholic solvents within the equipment during granulation processes. These systems recirculate solvents, reducing emissions and minimising environmental impact.

Temperature Control: Precise temperature control features are critical for handling alcoholic solvents to prevent solvent evaporation or condensation. Equipment should include heating or cooling capabilities to regulate temperature as needed.

Safety Interlocks and Alarms: Granulation equipment should be equipped with safety interlocks and alarms to monitor solvent levels, pressure, temperature, and other critical parameters. These features help prevent accidents and ensure compliance with safety regulations.

anish equipment emerges as the trusted ally for pharmaceutical manufacturers endeavouring to achieve flawless granulation processes across various solvent types. Our equipment’s adeptness in handling diverse solvents provides unparalleled versatility, efficiency, and safety within pharmaceutical manufacturing operations. This adaptability simplifies production workflows and guarantees unwavering product quality and adherence to stringent regulatory standards. By embracing our equipment, manufacturers can boldly tackle the intricacies of solvent-based granulation, optimise resource allocation, and propel their manufacturing endeavours to unprecedented levels of success.