Tablet
Content
TABLET
Disintegrant
Disintegrant is an excipient which is added to a tablet or capsule blend to aid in the break up of the compacted mass when it is put into a fluid environment. This is especially important for immediate release products where rapid release of drug substance is required.Disintegrant can be used with products that are wet granulated, dry granulated and direct compression. In wet granulation formulations, the disintegrant is normally effective when incorporated into the granule (intragranularly). It may be more effective if added 50% intragranularly, and 50% extragranularly. The simplest way to achieve quick disintegration is to use a superdisintegrant in concert with suitable diluents. Superdisintegrants such as croscarmellose sodium, crospovidone, and sodium starch glycolate are frequently used in tablet formulations to improve the rate and extent of tablet disintegration and thereby increase the rate of drug dissolution. There are three major mechanisms and factors affecting tablet disintegration as follows: A: Swelling: Although not all effective disintegrants swell in contact with water, swelling is believed to be a mechanism in which certain disintegrating agents (such as starch) impart the disintegrating effect. By swelling in contact with water, the adhesiveness of other ingredients in a tablet is overcome causing the tablet to fall apart. B: Porosity and Capillary Action (Wicking): Effective disintegrants that do not swell are believed to impart their disintegrating action through porosity and capillary action. Tablet porosity provides pathways for the penetration of fluid into tablets. The disintegrant particles (with low cohesiveness & compressibility) themselves act to enhance porosity and provide these pathways into the tablet. Liquid is drawn up or ³wicked´ into these pathways through capillary action and rupture the interparticulate bonds causing the tablet to break apart. C: Deformation: Starch grains are generally thought to be ³elastic´ in nature meaning that grains that are deformed under pressure will return to their original shape when that pressure is removed. But, with the compression forces involved in tableting, these grains are believed to be deformed more permanently and are said to be ³energy rich´ with this energy being released upon exposure to water. In other words, the ability for starch to swell is higher in ³energy rich´ starch grains than it is for starch grains that have not been deformed under pressure. It is believed that no single mechanism is responsible for the action of most disintegrants. But rather, it is more likely the result of inter-relationships between these major mechanisms. Disintegrants 1. Croscarmellose Sodium (Explotab, Primogel) : High swelling capacity with minimal gelling, effective at low concentrations ( 2.0% - 6.0%). Above 8%, disintegration times may actually increase due to gelling and its subsequent viscosity producing effects. 2. Crospovidone (Polyplasdone XL, Kollidon CL) : water insoluble and strongly hydrophilic. Rapidly disperses and swells in water, but does not gel even after prolonged exposure. Greatest rate of swelling compared to other disintegrants. Greater surface
area to volume ratio than other disintegrants. Recommended concentration: 1 to 3%. Available in micronized grades if needed to improve uniform dispersion in the powder blend. Sometimes, the surface of tablet after compression will be look ³pimpled´, especially in wet granulation. 3. L-HPC (Low-substituted hydroxypropyl cellulose) : Insoluble in water. Rapidly swells in water. Grades LH-11 and LH-21 exhibit the greatest degree of swelling. Certain grades can also provide some binding properties while retaining disintegration capacity. Recommended concentration 1-5%. Sodium Starch Glycolate Absorbs water rapidly, resulting in swelling which leads to rapid disintegration of tablets and granules. Recommended concentration: 1.0 ± 4.0% but may need to use up to 6.0%. Gels on prolonged exposure to water. High concentrations may cause gelling and loss of disintegration 4. Modified Cellulose- Internally cross-linked form of Sodium carboxymethyl cellulose. (Accelerates Dissolution), Nymcel.Wicking due to fibrous structure, swelling with minimal gelling. Effective Concentrations: 1-3% (Direct Compression), 24% (Wet Granulation) ADVANTAGES:
y y y
Effective in lower concentrations than starch Less effect on compressibility and flow ability More effective intragranularly
DISADVANTAGES:
y y
More hygroscopic (may be a problem with moisture sensitive drugs) Some are anionic and may cause some slight in-vitro binding with cationic drugs (not a problem in-vivo.)
Working Through Disintegrant The tablets of crospovidone exhibit significantly higher hardness than do those of croscarmellose sodium. Croscarmellose sodium aids in the disintegration and dissolution of pharmaceutical tablets, capsules, and granules. Coprocessing has been extensively examined for diluents. Croscarmellose sodium and crospovidone were selected in the present investigation since crospovidone acts by wicking action and croscarmellose sodium acts mainly by swelling action. Therefore, the superdisintegrants complement each other, accelerating the disintegration process when used together. The water uptake by the tablet is facilitated by the wicking action of crospovidone, while the tablet disintegration is facilitated by the swelling force exhibited by croscarmellose sodium. WHAT ARE DISINTEGRANTS? Disintegrants are agents added to tablet (and some encapsulated) formulations to promote the breakup of the tablet (and capsule ³slugs¶) into smaller fragments in an aqueous environment thereby increasing the available surface area and promoting a more rapid release of the drug substance.
There are three major mechanisms and factors affecting tablet disintegration as follows: A: Swelling:
Although not all effective disintegrants swell in contact with water, swelling is believed to be a mechanism in which certain disintegrating agents (such as starch) impart the disintegrating effect. By swelling in contact with water, the adhesiveness of other ingredients in a tablet is overcome causing the tablet to fall apart. B: Porosity and Capillary Action (Wicking):
Effective disintegrants that do not swell are believed to impart their disintegrating action through porosity and capillary action. Tablet porosity provides pathways for the penetration of fluid into tablets. The disintegrant particles (with low cohesiveness & compressibility) themselves act to enhance porosity and provide these pathways into the tablet. Liquid is drawn up or ³wicked´ into these pathways through capillary action and rupture the interparticulate bonds causing the tablet to break apart. C: Deformation:
Starch grains are generally thought to be ³elastic´ in nature meaning that grains that are deformed under pressure will return to their original shape when that pressure is removed. But, with the compression forces involved in tableting, these grains are believed to be deformed more permanently and are said to be ³energy rich´ with this energy being released upon exposure to water. In other words, the ability for starch to swell is higher in ³energy rich´ starch grains than it is for starch grains that have not been deformed under pressure. It is believed that no single mechanism is responsible for the action of most disintegrants. But rather, it is more likely the result of inter-relationships between these major mechanisms. The classical example of the earliest known disintegrant is Starch. Corn Starch or Potato Starch was recognized as being the ingredient in tablet formulations responsible for disintegration as early as 1906 (even though tablet disintegration was itself not given much importance in tablet formulations until much later). Until fairly recently, starch was the only excipient used as a disintegrant. To be effective, corn starch has to be used in concentrations of between 5-10%. Below 5%, there is insufficient ³channels´ available for wicking (and subsequent swelling) to take place. Above 10%, the incompressibility of starch makes it difficult to compress tablets of sufficient hardness. Although the connection between bioavailability of drug and tablet disintegration took some time to become appreciated, it is now accepted that the role of the disintegrant is extremely important. Other factors which affect the dissolution of Drugs from tablets are:
y y y y y y
Type and Concentration of Active Ingredient Type and Concentration of Binder Used Type and Concentration of Fillers Used (soluble vs. insoluble) Type and Concentration of Lubricant Used Type of Dissolution testing Used (Apparatus, Speed, Media) Manufacturing Process (wet granulation vs. compaction vs. direct compression)
In a direct compression process, drug is blended with a variety of excipients, subsequently lubricated and directly compressed into a tablet. A disintegrant used in this type of formulation, simply has to break the tablet apart to expose the drug substance for dissolution. In a wet granulation process, the drug substance is combined with other excipients and processed with the use of a solvent (aqueous or organic) with subsequent drying and milling to produce granules. The resulting granules are then blended with additional excipients prior to being compressed into a tablet. {Dry compaction is similar. But compression and milling are used (rather than solvents) to make the granules} A disintegrant used in granulated formulation processes can be more effective if used both ³intragranularly´ and ³extragranularly´ thereby acting to break the tablet up into granules and having the granules further disintegrate to release the drug substance into solution. However, the portion of disintegrant added intragranularly (in wet granulation processes) is usually not as effective as that added extragranularly due to the fact that it is exposed to wetting and drying (as part of the granulation process) which reduces the activity of the disintegrant. Since a compaction process does not involve its exposure to wetting and drying, the disintegrant used intragranularly tends to retain good disintegration activity. In addition to starch, the following are some of the disintegrants which were available prior to the use of the ³super-disintegrants´ to be discussed later: Pregelatinized Starch (Starch 1500) Pregelatinized starch is a directly compressible form of starch consisting of intact and partially hydrolyzed ruptured starch grains. Pregelatinized starch has multiple uses in formulations as a binder, filler and disintegrant. As a disintegrant, its effective use concentration is between 510%. It¶s major mechanism of action as a disintegrant is thought to be through swelling. Microcrystalline Cellulose (Avicel) Like pregelatinized starch, microcrystalline cellulose is widely used in formulations because of its excellent flow and binding properties. It is also an effective tablet disintegrant when used in a concentration of between 10-20%. Others Sodium Bicarbonate in combination with citric or tartaric acids is used as an ³effervescent´ disintegrant. Alginic Acid at a concentration of between 5-10% is an effective, but very expensive disintegrant. Ion Exchange Resins (Amberlite 88) has disintegrant properties at a concentration of between 1-5%. But this type of disintegrant is rarely used. SUPER DISINTEGRANTS: Because of the increased demands for faster dissolution requirements, there are now available, a new generation of ³Super Disintegrants´ in addition to the disintegrants discussed earlier. Three major groups of compounds have been developed which swell to many times their original size when placed in water while producing minimal viscosity effects: 1. Modified Starches- Sodium Carboxymethyl Starch (Chemically treated Potato Starch) i.e. Sodium Starch Glycolate (Explotab, Primogel) Mechanism of Action: Rapid and extensive swelling with minimal gelling.
Effective Concentration: 4-6%. Above 8%, disintegration times may actually increase due to gelling and its subsequent viscosity producing effects. 2. Cross-linked polyvinylpyrrolidone- water insoluble and strongly hydrophilic. i.e. crospovidone (Polyplasdone XL, Kollidon CL) Mechanism of Action: Water wicking, swelling and possibly some deformation recovery. Effective Concentration: 2-4% 3. Modified Cellulose- Internally cross-linked form of Sodium carboxymethyl cellulose. i.e. Ac-Di-Sol (Accelerates Dissolution), Nymcel Mechanism of Action: Wicking due to fibrous structure, swelling with minimal gelling. Effective Concentrations: 1-3% (Direct Compression), 2-4% (Wet Granulation) ADVANTAGES:
y y y
Effective in lower concentrations than starch Less effect on compressibility and flow ability More effective intragranularly
DISADVANTAGES:
y y
More hygroscopic (may be a problem with moisture sensitive drugs) Some are anionic and may cause some slight in-vitro binding with cationic drugs (not a problem in-vivo.)
BINDER USED in WET GRANULATION
Binder can be a sugar and polymer. Natural polymers binder: starch, gum (Acacia, tragacanth, gelatin) Synthetic polymers binder: PVP, methylcellulose, ethylcellulosa, hidroxypropylcellulosa\ Can be used in dry or wet granulation. Wet method requires less material.\ The amount of binder solution required for the 3 kg of filler are listed in the table 1. Starch (Amylum) Can be used as a filler, binder, and the disintegrant In the form of starch amili 5-10% Preparation :suspend starch 1:1 / 2-1 in cold water, add boiling water 2-4 times with constant stirring until the starch that can expand into a transparent diluted Another way: a suspension of starch in water heated Contains 11-14% water content, will cause the tablet disintegrated quickly - The making must be careful in order to obtain a good starch, is not hydrolyzed, and not making Best Use of a maximum of 30%. If a large dose of active ingredient, starch was replaced with a better disintegrant, namely Avicel.
Tablets containing a high concentration of starch tablets showed a fragile and difficult to be dried Unmodified starch does not have good compressibility properties and have a great friability, and the occurrence of capping in tablets if used in large quantities As disintegrant: Usage: 1-20%, is the most commonly used disintegrant Mechanism of action by forming hydrogen bonds during compression and rupture or expand when water entered Mell pore (capillary) Use is tailored to the type of starch, compression pressure, and water content of the mass Caution: C to remove absorbedrbefore use, starch must be dried at a temperature of 80-90 water 2. Starch 1500 Can be used as a binder in wet & dry granulation, and disintegrant Starch 1500 containing 20% maximum water-soluble fraction that functions as a binder while the rest are as disintegrant Starch 1500 takes 3-4 times as much starch amylum to produce tablets with the same hardness Should not be used as a filler in wet granulation because it will produce a gel that serves as a powerful binder As disintegrant, can be added in dry state, in the outer phase. The good flow is directly compressible starch Can be compressed own, but if mixed with 5-10% of drugs requires additional lubricant (eg, 0.25% colloidal silicon dioxide) Containing 10% moisture and cause the tablets become soft when combined with magnesium stearate> 0.5%, stearic acid used as a substitute As disintegrant: Represents good disintegrant and added to the dry mixture (in inner phase or outer phase in dry granulation or direct compression, or in the external phase on the wet granulation method) Caution: should not be given to the wet mass 3. Pregelatinized Starch It is a starch that has been cooked and dried again. Can be used as a substitute for starch paste is more easily soluble in warm water without heating Can be added to dry into a powder and then moistened with water to form moist mass
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Labels: Artesunate and Amodiaquine Tablet Formulation, Binder, Excipients, Extended Release Formulations of Metformin HCl 1000 mg by Wet Granulation
The Application of Starch 1500 (Pregelatinized Starch) in Solid Dosage Form
Pregelatinized starches have been used for a long time in the food industry, so does in Pharmaceutical industries. Starch 1500 is a unique pharmaceutical excipient combining several properties in a single product. Starch 1500 had multiple functions, such as binder, disintegrant, and flow-aid while having lubricant properties. It is extremely versatile, being effective in a variety of processing methods for solid oral dosage forms, such as direct compression, wet granulation, dry granulation/roller
compaction and encapsulation. Starch 1500 is particularly effective with moisture sensitive actives and low dose applications and exhibits synergy, enhancing the functionality of other commonly used excipients in formulations. The Advantages of Pregelatinized Starch (Starch 1500) Starch 1500 also has self-lubricating properties, which reduces the need for high levels of lubricants, thus improving mechanical strength and dissolution of the product. Pregelatinized starches had ability to thicken or gel promptly without the application of a substantial amount of heat necessary with normal starches. However, this ability to rapidly thicken or gel creates problems when these materials are used in dry products to be reconstituted in small portions by the ultimate consumer.
DISINTEGRANT USED IN WET GRANULATION
Function: to split tablets How to use: - when granulation - Before compressing (the best) 1. Starch (Amylum) 2. Starch 1500 3. Sodium starch glycolate (primogel, explotab) Usage: 1-20% with optimum concentration : 4% Explotab can not be use as disintegrant in inner phase Mechanism similar to starch in general, is a modified starch that can absorb water 200-300% Disintegration time is determined also by the amount of compression pressure Attention: at high temperature and high humidity can prolong disintegration time, slowing down the dissolution time 4. Cellulose (cellulose, methylcellulose, CMC, CMC-Na, Avicel, Acdisol) Acdisol is crosslinking of CMC-Na and excellent for use as disintegrant because water soluble and has a great affinity to water. Acdisol is listed on the super disintegrant. Usage: 2-5%.
The Important Parameter in Tablet Coating Process
Parameters Influences in Tablet Coating Process Tablet coating is a complex process that is affected by many variables. Some of those variables can be evaluated or controlled, others can¶t. Here are some of the parameters you should check when evaluating coating process to determine the source of defective coated tablets. 1. Control. Many problems occur in coating when you can¶t control every important parameter, such as temperature, pan pressure, spray rates, and atomization pressure. But, the tablet¶s
surface temperature can be measure with additional tools (out from the coating equipment) by using infra red thermometer (laser thermometer).
2. Tablet quality. Tablets must have the proper porosity, surface, hardness, and moisture content. You can¶t have consistent coating without consistent tablet quality. 3. Waiting period. Most tablets cannot be coated immediately after they¶ve been compressed. The energy within the tablets is still fairly high and they are still warm. In addition, tablet hardness changes over 24 to 48 hours. Let the tablets rest at least that long before you coat them meanwhile you can check the uncoated tablet for assay, dissolution or other specification by quality control. After the QC released the tablet, then you can start the coating process.
Disintegrant
Disintegrant is an excipient which is added to a tablet or capsule blend to aid in the break up of the compacted mass when it is put into a fluid environment. This is especially important for immediate release products where rapid release of drug substance is required.Disintegrant can be used with products that are wet granulated, dry granulated and direct compression. In wet granulation formulations, the disintegrant is normally effective when incorporated into the granule (intragranularly). It may be more effective if added 50% intragranularly, and 50% extragranularly. The simplest way to achieve quick disintegration is to use a superdisintegrant in concert with suitable diluents. Superdisintegrants such as croscarmellose sodium, crospovidone, and sodium starch glycolate are frequently used in tablet formulations to improve the rate and extent of tablet disintegration and thereby increase the rate of drug dissolution. There are three major mechanisms and factors affecting tablet disintegration as follows: A: Swelling: Although not all effective disintegrants swell in contact with water, swelling is believed to be a mechanism in which certain disintegrating agents (such as starch) impart the disintegrating effect. By swelling in contact with water, the adhesiveness of other ingredients in a tablet is overcome causing the tablet to fall apart. B: Porosity and Capillary Action (Wicking): Effective disintegrants that do not swell are believed to impart their disintegrating action through porosity and capillary action. Tablet porosity provides pathways for the penetration of fluid into tablets. The disintegrant particles (with low cohesiveness & compressibility) themselves act to enhance porosity and provide these pathways into the tablet. Liquid is drawn up or ³wicked´ into these pathways through capillary action and rupture the interparticulate bonds causing the tablet to break apart. C: Deformation: Starch grains are generally thought to be ³elastic´ in nature meaning that grains that are deformed under pressure will return to their original shape when that pressure is removed. But, with the compression forces involved in tableting, these grains are believed to be deformed more permanently and are said to be ³energy rich´ with this energy being released upon exposure to water. In other words, the ability for starch to swell is higher in ³energy rich´ starch grains than it is for starch grains that have not been deformed under pressure. It is believed that no single mechanism is responsible for the action of most disintegrants. But rather, it is more likely the result of inter-relationships between these major mechanisms. Disintegrants 1. Croscarmellose Sodium (Explotab, Primogel) : High swelling capacity with minimal gelling, effective at low concentrations ( 2.0% - 6.0%). Above 8%, disintegration times may actually increase due to gelling and its subsequent viscosity producing effects. 2. Crospovidone (Polyplasdone XL, Kollidon CL) : water insoluble and strongly hydrophilic. Rapidly disperses and swells in water, but does not gel even after prolonged exposure. Greatest rate of swelling compared to other disintegrants. Greater surface
area to volume ratio than other disintegrants. Recommended concentration: 1 to 3%. Available in micronized grades if needed to improve uniform dispersion in the powder blend. Sometimes, the surface of tablet after compression will be look ³pimpled´, especially in wet granulation. 3. L-HPC (Low-substituted hydroxypropyl cellulose) : Insoluble in water. Rapidly swells in water. Grades LH-11 and LH-21 exhibit the greatest degree of swelling. Certain grades can also provide some binding properties while retaining disintegration capacity. Recommended concentration 1-5%. Sodium Starch Glycolate Absorbs water rapidly, resulting in swelling which leads to rapid disintegration of tablets and granules. Recommended concentration: 1.0 ± 4.0% but may need to use up to 6.0%. Gels on prolonged exposure to water. High concentrations may cause gelling and loss of disintegration 4. Modified Cellulose- Internally cross-linked form of Sodium carboxymethyl cellulose. (Accelerates Dissolution), Nymcel.Wicking due to fibrous structure, swelling with minimal gelling. Effective Concentrations: 1-3% (Direct Compression), 24% (Wet Granulation) ADVANTAGES:
y y y
Effective in lower concentrations than starch Less effect on compressibility and flow ability More effective intragranularly
DISADVANTAGES:
y y
More hygroscopic (may be a problem with moisture sensitive drugs) Some are anionic and may cause some slight in-vitro binding with cationic drugs (not a problem in-vivo.)
Working Through Disintegrant The tablets of crospovidone exhibit significantly higher hardness than do those of croscarmellose sodium. Croscarmellose sodium aids in the disintegration and dissolution of pharmaceutical tablets, capsules, and granules. Coprocessing has been extensively examined for diluents. Croscarmellose sodium and crospovidone were selected in the present investigation since crospovidone acts by wicking action and croscarmellose sodium acts mainly by swelling action. Therefore, the superdisintegrants complement each other, accelerating the disintegration process when used together. The water uptake by the tablet is facilitated by the wicking action of crospovidone, while the tablet disintegration is facilitated by the swelling force exhibited by croscarmellose sodium. WHAT ARE DISINTEGRANTS? Disintegrants are agents added to tablet (and some encapsulated) formulations to promote the breakup of the tablet (and capsule ³slugs¶) into smaller fragments in an aqueous environment thereby increasing the available surface area and promoting a more rapid release of the drug substance.
There are three major mechanisms and factors affecting tablet disintegration as follows: A: Swelling:
Although not all effective disintegrants swell in contact with water, swelling is believed to be a mechanism in which certain disintegrating agents (such as starch) impart the disintegrating effect. By swelling in contact with water, the adhesiveness of other ingredients in a tablet is overcome causing the tablet to fall apart. B: Porosity and Capillary Action (Wicking):
Effective disintegrants that do not swell are believed to impart their disintegrating action through porosity and capillary action. Tablet porosity provides pathways for the penetration of fluid into tablets. The disintegrant particles (with low cohesiveness & compressibility) themselves act to enhance porosity and provide these pathways into the tablet. Liquid is drawn up or ³wicked´ into these pathways through capillary action and rupture the interparticulate bonds causing the tablet to break apart. C: Deformation:
Starch grains are generally thought to be ³elastic´ in nature meaning that grains that are deformed under pressure will return to their original shape when that pressure is removed. But, with the compression forces involved in tableting, these grains are believed to be deformed more permanently and are said to be ³energy rich´ with this energy being released upon exposure to water. In other words, the ability for starch to swell is higher in ³energy rich´ starch grains than it is for starch grains that have not been deformed under pressure. It is believed that no single mechanism is responsible for the action of most disintegrants. But rather, it is more likely the result of inter-relationships between these major mechanisms. The classical example of the earliest known disintegrant is Starch. Corn Starch or Potato Starch was recognized as being the ingredient in tablet formulations responsible for disintegration as early as 1906 (even though tablet disintegration was itself not given much importance in tablet formulations until much later). Until fairly recently, starch was the only excipient used as a disintegrant. To be effective, corn starch has to be used in concentrations of between 5-10%. Below 5%, there is insufficient ³channels´ available for wicking (and subsequent swelling) to take place. Above 10%, the incompressibility of starch makes it difficult to compress tablets of sufficient hardness. Although the connection between bioavailability of drug and tablet disintegration took some time to become appreciated, it is now accepted that the role of the disintegrant is extremely important. Other factors which affect the dissolution of Drugs from tablets are:
y y y y y y
Type and Concentration of Active Ingredient Type and Concentration of Binder Used Type and Concentration of Fillers Used (soluble vs. insoluble) Type and Concentration of Lubricant Used Type of Dissolution testing Used (Apparatus, Speed, Media) Manufacturing Process (wet granulation vs. compaction vs. direct compression)
In a direct compression process, drug is blended with a variety of excipients, subsequently lubricated and directly compressed into a tablet. A disintegrant used in this type of formulation, simply has to break the tablet apart to expose the drug substance for dissolution. In a wet granulation process, the drug substance is combined with other excipients and processed with the use of a solvent (aqueous or organic) with subsequent drying and milling to produce granules. The resulting granules are then blended with additional excipients prior to being compressed into a tablet. {Dry compaction is similar. But compression and milling are used (rather than solvents) to make the granules} A disintegrant used in granulated formulation processes can be more effective if used both ³intragranularly´ and ³extragranularly´ thereby acting to break the tablet up into granules and having the granules further disintegrate to release the drug substance into solution. However, the portion of disintegrant added intragranularly (in wet granulation processes) is usually not as effective as that added extragranularly due to the fact that it is exposed to wetting and drying (as part of the granulation process) which reduces the activity of the disintegrant. Since a compaction process does not involve its exposure to wetting and drying, the disintegrant used intragranularly tends to retain good disintegration activity. In addition to starch, the following are some of the disintegrants which were available prior to the use of the ³super-disintegrants´ to be discussed later: Pregelatinized Starch (Starch 1500) Pregelatinized starch is a directly compressible form of starch consisting of intact and partially hydrolyzed ruptured starch grains. Pregelatinized starch has multiple uses in formulations as a binder, filler and disintegrant. As a disintegrant, its effective use concentration is between 510%. It¶s major mechanism of action as a disintegrant is thought to be through swelling. Microcrystalline Cellulose (Avicel) Like pregelatinized starch, microcrystalline cellulose is widely used in formulations because of its excellent flow and binding properties. It is also an effective tablet disintegrant when used in a concentration of between 10-20%. Others Sodium Bicarbonate in combination with citric or tartaric acids is used as an ³effervescent´ disintegrant. Alginic Acid at a concentration of between 5-10% is an effective, but very expensive disintegrant. Ion Exchange Resins (Amberlite 88) has disintegrant properties at a concentration of between 1-5%. But this type of disintegrant is rarely used. SUPER DISINTEGRANTS: Because of the increased demands for faster dissolution requirements, there are now available, a new generation of ³Super Disintegrants´ in addition to the disintegrants discussed earlier. Three major groups of compounds have been developed which swell to many times their original size when placed in water while producing minimal viscosity effects: 1. Modified Starches- Sodium Carboxymethyl Starch (Chemically treated Potato Starch) i.e. Sodium Starch Glycolate (Explotab, Primogel) Mechanism of Action: Rapid and extensive swelling with minimal gelling.
Effective Concentration: 4-6%. Above 8%, disintegration times may actually increase due to gelling and its subsequent viscosity producing effects. 2. Cross-linked polyvinylpyrrolidone- water insoluble and strongly hydrophilic. i.e. crospovidone (Polyplasdone XL, Kollidon CL) Mechanism of Action: Water wicking, swelling and possibly some deformation recovery. Effective Concentration: 2-4% 3. Modified Cellulose- Internally cross-linked form of Sodium carboxymethyl cellulose. i.e. Ac-Di-Sol (Accelerates Dissolution), Nymcel Mechanism of Action: Wicking due to fibrous structure, swelling with minimal gelling. Effective Concentrations: 1-3% (Direct Compression), 2-4% (Wet Granulation) ADVANTAGES:
y y y
Effective in lower concentrations than starch Less effect on compressibility and flow ability More effective intragranularly
DISADVANTAGES:
y y
More hygroscopic (may be a problem with moisture sensitive drugs) Some are anionic and may cause some slight in-vitro binding with cationic drugs (not a problem in-vivo.)
BINDER USED in WET GRANULATION
Binder can be a sugar and polymer. Natural polymers binder: starch, gum (Acacia, tragacanth, gelatin) Synthetic polymers binder: PVP, methylcellulose, ethylcellulosa, hidroxypropylcellulosa\ Can be used in dry or wet granulation. Wet method requires less material.\ The amount of binder solution required for the 3 kg of filler are listed in the table 1. Starch (Amylum) Can be used as a filler, binder, and the disintegrant In the form of starch amili 5-10% Preparation :suspend starch 1:1 / 2-1 in cold water, add boiling water 2-4 times with constant stirring until the starch that can expand into a transparent diluted Another way: a suspension of starch in water heated Contains 11-14% water content, will cause the tablet disintegrated quickly - The making must be careful in order to obtain a good starch, is not hydrolyzed, and not making Best Use of a maximum of 30%. If a large dose of active ingredient, starch was replaced with a better disintegrant, namely Avicel.
Tablets containing a high concentration of starch tablets showed a fragile and difficult to be dried Unmodified starch does not have good compressibility properties and have a great friability, and the occurrence of capping in tablets if used in large quantities As disintegrant: Usage: 1-20%, is the most commonly used disintegrant Mechanism of action by forming hydrogen bonds during compression and rupture or expand when water entered Mell pore (capillary) Use is tailored to the type of starch, compression pressure, and water content of the mass Caution: C to remove absorbedrbefore use, starch must be dried at a temperature of 80-90 water 2. Starch 1500 Can be used as a binder in wet & dry granulation, and disintegrant Starch 1500 containing 20% maximum water-soluble fraction that functions as a binder while the rest are as disintegrant Starch 1500 takes 3-4 times as much starch amylum to produce tablets with the same hardness Should not be used as a filler in wet granulation because it will produce a gel that serves as a powerful binder As disintegrant, can be added in dry state, in the outer phase. The good flow is directly compressible starch Can be compressed own, but if mixed with 5-10% of drugs requires additional lubricant (eg, 0.25% colloidal silicon dioxide) Containing 10% moisture and cause the tablets become soft when combined with magnesium stearate> 0.5%, stearic acid used as a substitute As disintegrant: Represents good disintegrant and added to the dry mixture (in inner phase or outer phase in dry granulation or direct compression, or in the external phase on the wet granulation method) Caution: should not be given to the wet mass 3. Pregelatinized Starch It is a starch that has been cooked and dried again. Can be used as a substitute for starch paste is more easily soluble in warm water without heating Can be added to dry into a powder and then moistened with water to form moist mass
Read more »
Labels: Artesunate and Amodiaquine Tablet Formulation, Binder, Excipients, Extended Release Formulations of Metformin HCl 1000 mg by Wet Granulation
The Application of Starch 1500 (Pregelatinized Starch) in Solid Dosage Form
Pregelatinized starches have been used for a long time in the food industry, so does in Pharmaceutical industries. Starch 1500 is a unique pharmaceutical excipient combining several properties in a single product. Starch 1500 had multiple functions, such as binder, disintegrant, and flow-aid while having lubricant properties. It is extremely versatile, being effective in a variety of processing methods for solid oral dosage forms, such as direct compression, wet granulation, dry granulation/roller
compaction and encapsulation. Starch 1500 is particularly effective with moisture sensitive actives and low dose applications and exhibits synergy, enhancing the functionality of other commonly used excipients in formulations. The Advantages of Pregelatinized Starch (Starch 1500) Starch 1500 also has self-lubricating properties, which reduces the need for high levels of lubricants, thus improving mechanical strength and dissolution of the product. Pregelatinized starches had ability to thicken or gel promptly without the application of a substantial amount of heat necessary with normal starches. However, this ability to rapidly thicken or gel creates problems when these materials are used in dry products to be reconstituted in small portions by the ultimate consumer.
DISINTEGRANT USED IN WET GRANULATION
Function: to split tablets How to use: - when granulation - Before compressing (the best) 1. Starch (Amylum) 2. Starch 1500 3. Sodium starch glycolate (primogel, explotab) Usage: 1-20% with optimum concentration : 4% Explotab can not be use as disintegrant in inner phase Mechanism similar to starch in general, is a modified starch that can absorb water 200-300% Disintegration time is determined also by the amount of compression pressure Attention: at high temperature and high humidity can prolong disintegration time, slowing down the dissolution time 4. Cellulose (cellulose, methylcellulose, CMC, CMC-Na, Avicel, Acdisol) Acdisol is crosslinking of CMC-Na and excellent for use as disintegrant because water soluble and has a great affinity to water. Acdisol is listed on the super disintegrant. Usage: 2-5%.
The Important Parameter in Tablet Coating Process
Parameters Influences in Tablet Coating Process Tablet coating is a complex process that is affected by many variables. Some of those variables can be evaluated or controlled, others can¶t. Here are some of the parameters you should check when evaluating coating process to determine the source of defective coated tablets. 1. Control. Many problems occur in coating when you can¶t control every important parameter, such as temperature, pan pressure, spray rates, and atomization pressure. But, the tablet¶s
surface temperature can be measure with additional tools (out from the coating equipment) by using infra red thermometer (laser thermometer).
2. Tablet quality. Tablets must have the proper porosity, surface, hardness, and moisture content. You can¶t have consistent coating without consistent tablet quality. 3. Waiting period. Most tablets cannot be coated immediately after they¶ve been compressed. The energy within the tablets is still fairly high and they are still warm. In addition, tablet hardness changes over 24 to 48 hours. Let the tablets rest at least that long before you coat them meanwhile you can check the uncoated tablet for assay, dissolution or other specification by quality control. After the QC released the tablet, then you can start the coating process.
