Specific role of excipients in tablet production

Prepared By:DR. ANANDA KUMAR.CH

Assoc. Prof Department of pharmaceutics

Lydia college of pharmacy

Subject: Pharmaceutical Formulation

Pharm.D IIIrd Year

CONTENTS• Diluents • Binder• Disintegrants • Lubricants• Glidants and anticaking agents • Coloring agents• Sweetening agents • Coating agents

Diluents• These are components that are incorporated into tablet or capsule

dosage forms to increase volume and weight. Some times referred to as fillers, its often comprise a significant proportion of the dosage form, and the quantity and type of diluent selected often depends on its physical and chemical properties. Because may comprise a large portion of the dosage form, successful manufacturing and dosage form performance depend on the measurement and control of these critical attributes.

• Mechanism: its role is desirable manufacturing properties(eg: powder flow, tablet compact strength, wet or dry granule formation, homogeneity) and performance (eg: content uniformity, disintegration, dissolution, tablet integrity, friability, physical chemical stability . Some diluents (microcrystalline cellulose) occasionally dry binders because high degree of tablet strength they important to the final compressed tablet.

Diluents

• Physical properties: Tablet/ capsule primary properties are direct effect on diluent and formulation performance.

1. Particle size and size distribution 2. particle shape 3. bulk/ true/tapped density, 4. specific surface area 5. crystallinity, 6. moisture content, 7. powder flow, 8. solubility, 8. compaction.

Diluents and specific role: 2. Lactose ( anhydrous and monohydrate): it is used for direct

compression due to superior compressibility.3. Microcrystalline cellulose: it is used for direct compression

now included in granules due to its excellent compressibility.4. Dextrose or Glucose: direct compression , used in chewable

tablets

Diluents

4. Starch and Derivatives: Versatile material that can be used as diluent binder, disintegrant.

5. Calcium Carbonate: Brittle material, an inert material used as filler.

6. Dicalcium Phosphate: Excellent flow properties 7. Magnesium Carbonate: Direct compression diluent.Eg of Diluents: Kaolin Starch, Lactose, Pregelatinised starch,

Modified Cellulose, Tapioca Cellulose, Powdered Maltodextrin Starch, Wheat Starch Maltose, sucrose dextrin Mannitol, Sugar, Calcium Carbonate Etc….

Binder • These are incorporated into formulations to facilitate the

agglomeration of powder into granules during mixing with granulating fluid such as water, hydroalcoholic mixture, other solvents.

Mechanism: Tablet/ capsule binders are soluble or partially soluble in granulating solvent or in the case of native starches, can be made soluble. The concentrated binder solutions also have adhesive properties. Upon addition of liquid, binders typically facilitate the production of moist granules by altering interparticle adhesion.

Physical Properties: Dispersion/ dissolution of binder in the granulation liquid depends on its physical properties like surface tension, particle size distribution, solubility, viscosity is more important.

BinderSpecific binders role in tablet production:1. Starch: the most commonly used binder, it has to be prepared

as paste, before use.2. Pregelatinised starch: soluble in cold water so easy to

prepare than starch.3. Acacia: it used as preparation of paste, retard the

disintegration times if used at high concentration.4. Polyvinyl Pyrrolidone: available in the range of M.w,

viscosity; soluble in water and ethanol. 5. HPMC&Mc: low viscosity grades widely used.Eg: Acacia, Alginic acid, Ammonio Methacrylate Copolymer,

Corbomer Copolymer, Gelatin, Glucose, Guar Gum, HPC, Cellulose Maltodextrin, Povidone, Starch, Corn starch, Potato starch.

Disintegrants • Tablet formulation the breakdown of the tablet into granules when

it reaches the GIT fluid. In case of enteric coated or controlled release tablets disintegrants are an important in formulation(disintegration of conventional tablets occur within 15 min).

• Specific role in tablet production:1. Starch: capillary action and swelling minimal at body tem.2. MCC: strong capillary action3. Gum: swell on react with water; viscous gels that retard

dissolution, thus limiting conc. That can be used.4. Alginic acid: swell like gum but less viscous gel5. Sodium starch glycolate Croscarmalose sodium: when swell in

react with water and strong capillary action.

Mechanism Physical properties Examples It increase the porosity and wettability of the compressed tablet matrix. The gastrointestinal fluids may readily penetrate the tablet matrix they are often referred as super disintegrants.

It is insoluble in water and facilitating the transport of liquid into the core of tablet, with the consequence tablet breaks into fragments

Starch, MCC, gelatin, Gums, sodium starch.

It may operate by swelling in the presence of Aq. Fluids, there by expediting tablet disintegration due to increase in the internal pressure within the tablet matrix. They are often super disintegrants .

It is insoluble in water, absorb water and swell, facilitate the disintegration of the tablets.

sodium starch glycolate croscarmellose sodium ( a cross linked sodium carboxymethylcellulose)

Whenever the tablets reacts Aq. Fluid the tablet disintegration by the production of gas. it is mechanism of effervescent tablet.

Tablet contains a mixtue of sod. Bicarbonate and tartaric or citric acid will effervescent when added water

Sodium bicarbonate, tartaric acid, citric acid

lubricants• It used to reduce the fractional forces between particles and metal

contact surfaces of manufacturing equipment such as tablet punches and dies used in the manufacturing the solid dosage forms.

Mechanism Physical properties Examples It is adhering to solid surface and reducing the particle particle friction or the particle metal friction

The primary properties that are possibly important for boundary lubricants include particle size, surface area, hydration state, and polymirphic form.

Calcium Stearate, SLS, Talc, SSF, Vegetable oil, Hydrogenated, Mg. Stearate, Starch, Zinc Stearate, Mineral Oil, Light Stearic acid, Polyethylene Glycol

lubricants

Specific role in tablet production:1. Talc: fine crystalline powder used as lubricant and diluent

has small particle size and large surface area helps in covering surface imperfection of granules.

2. Silicon dioxide: used as adsorbent antitacking agent disintegrant and glidant .

3. Starch: used as binder, disintegrant, and diluent but also used for glidant.

4. SLS: anionic surfactant, lubricant, and wetting agent.5. Mg. Stearate and Mineral Oil: Hydrophobic can be applied

to either formulation or tooling

Glidants and anticaking agents• There are used to promote powder flow and reduce the caking

or clumping that can occur when powders are stored in bulk.

Mechanism Physical properties Examples

It is combination of adsorption onto the surface of larger particles and reduction of particle- particle adhesive and cohesive forces, thus particles to move more easily relative to one another.

Potential importance of glidants and anticaking agents are particle size, particle size distribution, and surface area. It may be slightly hygroscopic.

Calcium Silicate, Silicon dioxide, Colloidal Mg. Stearate, Talc.

Glidants and anticaking agentsSpecific role in tablet production:

1. Talc: fine crystalline powder used as lubricant and diluent has small particle size and large surface area helps to improve flowability.

2. Silicon dioxide: Flowability; used as adsorbent, anticaking agent, disintegrant, and glidant.

3. Calcium Silicate: Anticaking and free flow agent in chemicals, excellent water and oil absorption, carrying agent in animal feedstuff,

Coloring agents • They are incorporated into dosage forms in order to produce a

distinctive appearance that may serve to differentiate a particular formulation from others that have a similar physical appearance. These are subdivided into dyes (water soluble substances)

• Lakes: insoluble forms of a dye that result from its irreversible adsorption onto a hydrous metal oxide.

• Inorganic pigments: substance such as titanium dioxide or iron oxides

• Natural colorants: colored compounds not considered as dyes such as riboflavin .

*in the federal Food, Drug, Cosmetic act 1938 three categories of coloring agents were created.

1. FD&C colors: Those certifiable for use in coloring foods, drugs, and cosmetics.

2. D&C colors: Dyes and Pigments considered safe in drugs and cosmetics when in contact with mucous membranes or when ingested .

3. Ext. D&C colors: Colorants that because of their oral toxicity are not certifiable for use in ingestible products but are considered safe for use in externally applied products.

Mechanism Physical properties Examples Water soluble dyes are usually dissolved in a granulating fluid for use, although may also be adsorbed onto carriers such as starch, lactose, or sugar form aqueous or alcoholic solutions

Particle size and size distribution of dyes and lakes can influence product processing times (blending and dissolution), color intensity, and uniformity of appearance.

Ferric oxide, Red Ferric oxide, Yellow Ferric oxide Blends, Caramel.

Sweetening agents • They are used to sweeten oral dosage forms and to mask

unpleasant flavors.

Mechanism Physical properties Examples

It is bind to receptors on the tongue that are responsible for the sensation of sweetness. The longer the sweetener molecule remains attached to the receptor, the sweeter the substance is perceived to be. The standard for sweetness is sucrose.

The primary physical properties relevant to sweeteners relate to their compatibility with the other ingredients in the formulation.

Acesulfame,Aspartame, Maltose, Sucrose Saccharin Sugar, Dextrose Saccharin, Fructose, Sorbital Galactose and sorbitol Solution

Coating agents • The pharmaceutical drug delivery systems include masking

unpleasant taste or odors, improving ingestion. Improving appearance, protecting active ingredients from the environment, controlling the rate of release of the active ingredient, and controlling drug release in the gastrointestinal tract.

Specific role in tablet production:1. Methyl cellulose: Soluble in cold water, GI fluids, and a range of

organic solvents. 2. Ethyl cellulose: Soluble in organic solvents, insoluble in water and

GI fluids; used alone in modified release formulation and in combination with water- soluble cellulose for immediate release formulations.

3. Hydroxyl propyl methyl cellulose: soluble in cold water, GI fluids, alcohols.

4. Sodium carboxy methyl cellulose: soluble in water and polar solvents

Coating agentsMechanism Physical properties Examples

The coating system forms a layer on the substrate. Eg: a particle or unit dosage form, and changes its appearance. On contact with the secretions of the GIT, the coating makes the product slide more easily over mucosal surfaces and helps control the rate and site of drug release.

The necessary physical properties for a coating system include adequate mechanical strength. The film must be strong enough to withstand tumbling during the coating process and resist film erosion. The solubility of the coating material must be adequate in either aqueous or nonaqueous solvents, depending on the nature of the material

CMC, Cellulose Acetate< Cellulose Acetate Phthalate, EC, Gelatin, HPC, Methacrylic Acid Copolymer, MC, Poly ethylene Glycol, Polyvinyl Acetate Phthalate, Shellac, Starch, Wax, Carnuba Wax and Microcrystalline wax.