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
- 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
• Incompatible with: highly alkaline compound, ascorbic acid, salicylamide, pyrilamine maleate, phenilephrine HCl
• lactose hydrate granules contain 4-5% moisture content
• Lactose is the reductor sugar, reacts with amines to produce Maillard reaction
• Isomers: α and β (in the mixture are in equilibrium both forms)
• The most common filler, there are 2 forms: hydrated and anhydrous
• Rarely reacts with the drug (hydrated and anhydrous)
• For wet granulation use lactose hydrate. Anhydrous lactose did not experience Maillard reaction (with an active substance containing amines in the presence of metal stearate), but it absorbs moisture.
• In general, tablets show a good release rate, the granule quick to dry, disintegration of the tablets are not much affected by hardness.
• Disadvantages : lactose can change color in the presence of alkaline amines and Mg-stearate
• Known 4 kinds of forms: coarse granules (60-80 mesh), fine granules (80-100 mesh), spray dried granules (100-200 mesh), and anhydrous lactose
• Known as sugar milk.
• use as filler for direct compression, usually combined with Avicel. If it’s singular, used in a concentration of 40-50% as the carrier
• The nature of its direct compression is reduced if the water content <3%, can be mixed with 20-25% active substance without losing its properties of direct compression
• The capacity to hold the active substance 20-25%; have good flow and binding characteristics of lactose better than usual
• Disadvantages : can be blackened with a moist, amen, or other compounds containing furaldehid
• Use a neutral or acid lubricant
• Can act as filler or binder
• If used as sole binder, sucrose form hard granules and tablets were more likely be dissolved than disintegrated. Therefore, many in combination with other insoluble fillers
• If used as dry filler, usually granulated with water-soluble binder or hydroalcohol. Granules hardness depend on the amount of binder used. The mixture of water and alcohol will produce a softer granules.
• It has many forms, most commonly used form of "confectioner" for wet granulation containing 3% corn starch to prevent caking
• Sucrose is used as a sweetener in chewable tablet and is used as a binder to improve tablet hardness
• Disadvantages : tablets made with the composition of most of the sucrose will harden in storage. Sucrose rather than reducing sugars but become brown on storage and hygroscopic
• Derivatives of sucrose that can be used for direct compression:
a. Sugartab: 90-93% sucrose, 7-10% invert sugar
b. In the Pac: 97% sucrose, 3% modified dextrins
c. Nu Tab: 95% sucrose, 4% invert sugar, 1% corn starch, magnesium stearate
• Its application limited to wet granulation as filler and binder
• Used similar to sucrose, which tends to produce hard tablets, especially if using dextrose anhydrous
• To become brown on storage
• Good filler for chewable tablet because it’s taste good, slightly sweet, smooth, cool (negative heat solution)
• Non-hygroscopic, the flow is poor, needs more liquid binder
• Can be used for formulation of vitamins, produce finer granules than sucrose or dextrose
• Levels of moist granules are made from sucrose, dextrose, and mannitol after drying overnight at 140-150 0F is 0.2%
• Only a few absorbed in the gastrointestinal tract, if used a lot to be laxative
8. Emdex and Celutab
• Can react with amines at high temperature and high humidity
• Free flowing and can be compressed directly, containing 8-10% moisture, tablet hardness can be increased after compression
• Hydrolyzed starch containing 90-92% dextrose and 3-5% maltose
• Can be used as a substitute for mannitol in the chewable tablet as sweet and smooth taste.
9. Starch 1500