Binders play an important role in the tableting process of pharmaceuticals. They are used to improve the cohesion and plasticity of the powder mixture, which enhances the processability of the tablet and reduces the risk of tablet breakage during manufacture.
The quantity of binder excipient used in the tableting process varies depending on the specific application, but typically ranges from 2-10% of the tablet weight.
Binder are distinct from fillers and diluents, which have different functions in the tablet. Fillers are added to increase the bulk of the tablet, while diluents are added to reduce the potency of the active ingredient. Binder excipients, on the other hand, are added specifically to improve the tablet’s mechanical properties.
Ideal properties of tablet binder
• Physiologically inert.
• Acceptable to regulatory agencies.
• Physiologically ad chemically stable.
• Commercially available in a stable form.
• Meet the standards of regulatory requirements.
• Should not interfere with the bioavailability of the drug.
• Able to cohesive compacts for directly compressed tablets.
Effect of Binder in different properties of Tablet
Effect of binders on the mechanical strength of directly compressed tablets:
The addition of a binder to a compound has been suggested to change the surface proprieties of the coarse compound particles as they are covered by the small binder particles. It was proposed that this surface coverage increased the surface area available for inter particulate bonding, thus increasing the number of bonds and also possibly creating stronger bonds, with a subsequently increased mechanical strength (Nystrom et al., Dub erg and Nystrom, 1985; Nystrom and Glazer, 1985).
The addition of a binder that increases elasticity can decrease tablet strength because of the breakage of bonds as the compaction pressure is released (Nystrom C et al.,1982).
Effect of amount of binder and compaction pressure on tablet porosity:
Increasing the amount of binder added to a compound resulted in a gradual decrease in tablet porosity as more of the inter particulate voids were filled with the binder. For example, the addition of the binders most prone to undergo plastic deformation gave the most pronounced effect of the amount of binder of tablet porosity.
An increase in compaction pressure during tableting resulted in a gradual decrease in porosity as more of the inter particulate voids were filed with a binder. For example, the addition of the binders most prone to undergo plastic deformation gave the most pronounced effect of the amount of binder on tablet porosity.
An increase in compaction pressure during tableting resulted in a gradual decrease in porosity as the particles were brought into closer proximity to each other. It appeared that the effect of the binder on tablet porosity was generally more pronounced when the compaction pressure was low.
Effect of binder on tablet strength:
The addition of a binder to a compound generally increases the tablet strength. The increase in tablet strength was influenced by properties associated with both the binder and the compound and these will be dealt with in the followings section. The strength of tablets composed of some mixture was higher than that of tablets made often individual materials, referred to a synergistic effect.
Effect of binder deformability and particle size on tablet strength:
The addition of a binder with a high propensity for plastic deformation resulted in a pronounced increase in tablet strength compared to that of the pure compound. This result is associated with poor compatibility and moderate deformability that had only a small effect on both tablet strength and porosity.
Effect of amount of binder and compaction pressure on tablet strength:
Earlier studies regarding the amount of binder have suggested that the amount corresponding to a surface area ratio of unity, i.e., the amount required to cover the compound particles with the binder, resulted in the highest tablet strength [Nystrom et al.,1982]. The addition of a binder above this amount had less effect on tablet strength. The amount corresponding to a surface area ratio of unity was assumed to be necessary to increase and change the nature of the surface area available for inter particulate bonding and thereby increase tablet strength.
CLASSIFICATION ON THE BASIS OF THEIR APPLICATION:
1. Solution binders:
These are dissolved in a solvent (for example water or alcohol can be used in wet granulation processes). Examples include gelatin, cellulose, cellulose derivatives, polyvinyl pyrrolidone, starch, sucrose and polyethylene glycol.
2. Dry binders:
These are added to the powder blend, either after a wet granulation step, or as part of a direct powder compression (DC) formula. Examples include cellulose, methyl cellulose.
Binders can be of different origins and divided into
Natural Polymers: Arabic gum, Gelatin, Sodium Alginate, Pullulan, Starch, Pregelatinized Starch and Tragant
Semi-Synthetic Polymers: Carboxymethylcellulose Sodium, Dextrin, Hydroxyethylcellulose, Hydroxypropylcellulose, Hypromellose, Maltodextrin, Methylcellulose
Synthetic Polymers: Copovidone, Macrogols, Polyvinyl Alcohols (PVA), Povidone, Polymers with sustained release properties: Amino methacrylat-Copolymer (Type A),Aminomethacrylat-Copolymer (Typ B), Celluloseacetate,Celluloseacetatbutyrate, Chitosan, Ethylcellulose, Polyacrylat-Dispersion 30 %, Poly(vinylacetat), Poly(vinylacetat)-Dispersion 30, Schellack, Zein Other Binders with sustained release properties: Fatty alcohols, Fat and Waxes, Hydrated Rizinius Oil, Stearic Acid Many excipients can be used as binders. The main ones are
Povidone (Polyvinylpyrrolidone, PVP)
Hydroxypropyl cellulose (HPC)
Microcrystalline cellulose (MCC)
Polyethylene glycol (PEG)
Pregelatinized starch
Starch
Carbomers
Sodium carboxymethyl cellulose (NaCMC)
Definitions According to the European Pharmacopeia (Ph. Eur.) and USP/NF
Povidone (Polyvinylpyrrolidone, PVP) Ph. Eur.:
Povidone, which is alternately referred to as PVP, is recognized as a versatile excipient that is used in complexation, solubilization, and film applications in addition to being one of the most widely used granulation and tablet binders. PVP is manufactured by radical polymerization of N-vinylpyrrolidone. PVP is available in multiple MW grades ranging from 2 to *1500 kDA. The high MW grades have been reported to have very high binder efficiency, however, medium and low MW grades are most often used as granulation and tablet binders since high MW grades may impede dissolution behavior (Table 2). PVP is listed in the USP/NF, Ph. Eur., and JP (4). Much of its versatility derives from favorable solution behavior. Povidone is highly soluble in water and freely soluble in many polar organic solvents such as ethanol, methanol, isopropyl alcohol, and butanol. It is insoluble in nonpolar organic solvents. PVP is generally used in the form of a solution, where its low viscosity allows solids concentrations as high as 15% to 20%. PVP can also be added dry to a powder blend and then granulated with just the solvent, but as with MC and HPMC, binder efficiency is significantly lower in this case. Although use levels in the literature are reported as 2% to 5%, higher levels up to 10% may have to be used in challenging, poorly compactable formulations. PVP is highly hygroscopic, and at 50% RH, typical equilibrium moisture content exceeds 15% by weight. It is therefore advisable to take precautions against uncontrolled and unnecessary exposure to atmospheric moisture.
Hydroxypropyl cellulose (HPC) Ph. Eur.:
HPC has compendial status in the National Formulary (USP/NF), European Pharmacopoeia (Ph. Eur.), Japanese Pharmacopeia (JP), and Food Chemicals Codex (FCC). HPC is fully soluble in water and polar organic solvents such as methanol, ethanol, isopropyl alcohol, and acetone. Water solubility is temperature dependent with a cloud point around 45degC. HPC is a true thermoplastic polymer and has shown equivalent binder efficiency and good compactibility when added as a solution or in dry, powder form, before granulation . Various molecular weight (MW) grades are available ranging from 60 to 1000 kDa; however, low MW grades are most typically used as binders . Moreover, for dry addition, fine particle size grades (60–80 mm mean diameter) are preferred because of faster hydration and uniform mixing and distribution. Coarse grades are preferred for solution addition as they disperse more easily without lumping than dry grades. Lump-free aqueous solutions are best prepared by dispersing the powder in 30% of the required final volume of water at 658C. After 10 minutes of hydration the remaining water can then be added cold while continuing to stir. Because of its high binder efficiency, HPC tends to be particularly well suited for high-dose, difficult-to-compress tablets, where only small amounts of binder can be added. In general, use levels above 8% are not recommended as they tend to cause excessive slowing of disintegration and dissolution times. HPC is also frequently used in film coating and melt extrusion.
Microcrystalline cellulose (MCC) Ph. Eur.:
Microcrystalline Cellulose (MCC) is a very popular binder and diluent in tablet and capsule formulations due to its excellent compressibility, stability and safety.When used as binder and diluent in tablet formulation, it undergoes plastic deformation under pressure leading to hydrogen bonds between adjacent cellulose molecules. Tablets made with PARMCEL exhibit a very high tensile strength at even low compression forces, thus potentially reducing the wear on tableting tools. Despite forming hard tablets, PARMCEL does not affect the disintegration time. Due to the hydrophilic nature of cellulose, aqueous pores are formed after contact with water and leads to the disintegration of the tablet.
Polyethylene glycol (PEG) Ph. Eur.: A water-soluble polymer that can be used as a binder excipient in tablet formulations. USP/NF: A water-soluble polymer that is used as a lubricant and solubilizing agent in pharmaceutical formulations.
Gelatin Eur.: A protein derived from collagen that is used as a binder and gelling agent in pharmaceutical formulations. USP/NF: A protein derived from collagen that is used as a binder and gelling agent in tablet and capsule formulations.
Pregelatinized starch (PGS):
Pregelatinized starch (PGS) is classified as a modified starch. Chemical and mechanical treatment is used to rupture all or part of the native starch granules. Pregelatinization enhances starch cold-water solubility and also improves compactibility and flowability. PGS is marketed as a multifunctional excipient, providing binding, disintegration, good flow, and lubrication. PGS monographs can be found in the USP/NF, Ph. Eur., and JPE (6). It is typically used from solution in wet granulation; it can also be dry added, but this reduces efficiency significantly. Furthermore, at 15% to 20%, use levels are usually higher for PGS relative to other binders. PGS is not compatible with organic solvents and thus is used only in aqueous binder systems. While it tends to have high equilibrium moisture levels, starch is known to hold water in different states, that is, only a portion of the sorbed water will be available as “free” water. This property can be exploited by using starch as a stabilizer or moisture sequestrant. Partially pregelatinized starch is the most frequently used form of PGS, but fully pregelatinized starch is also available. The degree of pregelatinization determines cold water solubility. Commercial, partially pregelatinized starch typically has around 20% pregelatinized or water-soluble content. The cold water–soluble part acts as a binder, while the remainder aids tablet disintegration. For this reason, fully pregelatinized starches tend to have higher binder efficiency, but not necessarily good disintegrant properties.
Starch Eur.:
Starch has traditionally been one of the most widely used tablet binders, although today PGSs are often preferred. Starch is polysaccharide carbohydrate consisting of glucose monomers linked by glycosidic bonds. The main sources for excipient-grade starch are maize and potato starch. References to wheat, rice, and tapioca starch can also be found in the literature. Starch is a GRAS-listed material with monographs in the USP/NF, Ph. Eur., and JP. Starch is not cold water or alcohol soluble; traditionally, it is used by gelatinizing in hot water to form a paste. Starch paste can be prepared by heating a starch suspension up to the boiling point with constant stirring. Binder use levels for starch are usually relatively high (5–25%). The high viscosity of starch paste can make granulation, efficient binder distribution, and substrate wetting somewhat problematic, however, an advantage of starch is that it tends to enhance tablet disintegration.
Carbomers Eur.: A family of water-soluble polymers that are used as thickening and emulsifying agents in pharmaceutical formulations. USP/NF: A family of water-soluble polymers that are used as thickening and emulsifying agents in topical and oral pharmaceutical formulations.
Sodium carboxymethyl cellulose (NaCMC) Ph. Eur.: A cellulose derivative that is used as a binder and disintegrant in tablet formulations. USP/NF: A cellulose derivative that is used as a binder and thickener in pharmaceutical formulations.
In conclusion, binder excipients are essential components in the tableting process of pharmaceuticals. They improve the cohesion and plasticity of the powder mixture, enabling the manufacture of robust and uniform tablets. Binder excipients differ from fillers and diluents, which serve different functions in tablet formulations. A variety of excipients, including povidone, hydroxypropyl cellulose, microcrystalline cellulose, polyethylene glycol, gelatin, starch, carbomers, and sodium carboxymethyl cellulose, are commonly used in the pharmaceutical industry. The definitions of these excipients according to the European Pharmacopeia and USP/NF reflect their various applications in pharmaceutical formulations.
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