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: before use, starch must be dried at a temperature of 80-90C to remove absorbed 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

FILLER/DILUENT FOR WET GRANULATION

Is an inert substance that is added in tablet formula intended to create a tablet weight as expected.
Usually tablets containing the active substance with a small dose requires a lot of filler material. If the tablet has big dose of active substance, the filler slightly or not at all.

1. Avicel (Microcrystalline Cellulose)
• Avicel 103 has the advantage compared with 101, 102 because of small specific volume, better flow and a shorter disintegration time.
• Insoluble, non-reactive, the flow is not good, hold 50% capacity.
• Generate a hard tablet with a small pressure (compressibility good) and low friability tablets, long-time stability.
• Generate a fast wetting and thus distribute the liquid evenly to the entire mass of powder; produce drug distribution and a uniform color.
• Acting as an auxiliary binding, resulting in a hard granules with minimal fines.
• Can be act as dry binder, disintegrant, lubricant and glidan.
• Its use requires a lubricant; its use can be combined with lactose, mannitol, starch, calcium sulfate.
• Helps overcome substances that if overwetting (too wet) to something like "clay" is difficult and when dry granulated , the granule becomes hard and resistant to disintegration. Example: kaolin, calcium carbonate.
• Avicel in wet granulation improve ties in the compression, reducing the capping and friability of tablets.
• Avicel assist with water-soluble drugs for homogeneous, preventing migration of water soluble dyes and helps for quick evaporation and uniform.
• For drugs with small doses, Avicel used as a filler and binder addition.
• 60% Avicel PH 101 and 40% amylum as 10% starch as a paste made easy moist granulated mass, forming a strong granules on drying with less fine than that just paste made from starch.
• Form PH 101: powder, PH 102: granule, PH 103: powder

As disintegrant:
- It is a very good disintegrant, especially at concentrations of 10% or higher.
- In wet granulation method, Avicel don’t have disintegrant properties.
- Attention: at high concentrations, Avicel can cause sticky on the tongue.

2. Calcium sulfate trihydrate
• Used as a filler for granulation with the amount of active ingredient 20-30%.
- Synonym: terra alba, snow white filler.
- Insoluble, non-hygroscopic.
- The higher the grade, increasingly white, most inexpensive filler, the active substance can be used for acidic, neutral, alkaline, have high absorban capacity for oil.
- Binder suggested: PVP, Croscarmellose, starch paste.


3. Calcium phosphate dibasic
• Used as a filler and binder for direct compression with the smallest in size, not expensive, can not be used with acid compounds or acid salt
• If you use a liquid binder that is too much then so sticky and hard, can not be granulated so that the solution combined with the starch / Avicel


Properties of Some Tablet Ingredients

1. Fines
The maximum amount of fines is 30% of the weight of the tablet, including the outer phase. If the total amount of fines more than 30% big possibility capping will occur. Different amounts, different distributions can be resolved by Hoover that does not vibrate and / or a add stirrer on the compression machine.

2. Eksplotab
Eksplotab is not an acid-resistant ingredient and only use as disintegrant in the outer phase, can not be able to be used for wet granulation. Use 3-5%, maximum 25%.

3. Starch 1500
Filler for direct compression tablets. If there is water, it going into gel so that the active substances are blocked, power expands less so disintegrant time will be long. Use as tablet filler : no more than 30%.

4. Avicel pH 101,102,103 good for direct compression tablet

Tablets Effervecent Ingredients

It should be noted that the ingredients used in tablet effervescent should have the contents moist very low and when the manufacture of this preparation must be done in a dry place.

Characteristic of Effervescent tablet ingredients:

1. In many ways, the principles used in producing Effervescent tablets similar to those used for conventional tablets. Many of the processes and tools the same process. Likewise, the general nature of granules required for obtaining tablets according to the requirements such as:
  • Particle Size
  • Particle shape
  • Granulometri
  • Uniformity of distribution
  • Free flow of granules
  • Granules must be compressed

2. The nature of raw materials selected for use in Effervescent Tablets that more important than tablets conventional is the moisture content, which means the raw materials used must be dry.
If the raw material used is not dry (containing moisture), then acid reaction will occur the carbonate will cause the product to be physically unstable and decompose. Once started the reaction it will continue much faster because the byproducts reaction is water added.

Example:
CH2COOH CH2COONa
CH2COOH + 3NaHCO3 CHCOONa + 3 CO2 + 3 H2O
CH2COOH CH2COONa

Therefore, the raw materials used must be in anhydrous (dry) with a few levels humid absorbed. The water molecule is still there but very little because it takes a little water to bind the granules because if the granules too dry, granules can not be compressed.

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