Diluents 4q4243

Diluents PHRM 210

Diluents • Also known as bulking agents or fillers • Added to the active ingredient in sufficient quantity to make a reasonably sized tablet • A tablet should at least 50mg and therefore very low dose drugs (diazepam, clonidine hydrochloride) will invariably require a diluent to bring the overall tablet weight to at

Diluents • This agent may not be necessary if dose of drug per tablet is high (e.g. aspirin and certain antibiotics) • Usually the range of diluents may vary from 5-80%

Diluents: Primary reason of use • Inert substance designed to make up the required bulk of tablet when the drug dosage itself is inadequate to produce its bulk

Diluents: Secondary reason of use To provide better tablet properties such as: • Improved cohesion (maintain proper shape of tablet) • To permit use of direct compression manufacturing • To promotes flow • To adjust weight of tablet as per die capacity • 

Diluents INSOLUBLE TABLET DILUENTS

SOLUBLE TABLET DILUENTS

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• Starch • Powdered cellulose • Microcrystalline cellulose • Calcium phosphates

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• • • •

Lactose Sucrose Mannitol Sorbitol

Diluents: Lactose • Most widely used diluent in tablet formulation • Also used as a filler or diluent in capsule formulation • Several grades are available S u ita b le fo r  - Lactose (monohydrate) w et  - Anhydrous lactose g ra n u la tio n  - Spray dried lactose (better mixing)

Diluents: Lactose • Has no reaction with most drugs whether it is used in the hydrous or anhydrous form • Destroyed with amino compounds, lactates, acetates and alkaline lubricants • Lactose on storage tends to lose moisture

Diluents: Spray dried lactose • Spray dried lactose blended with microcrystalline cellulose constitutes a good directly compressible diluent • It may also be used as a disintegrant and a lubricant • If lactose is to be used as a directly compressible diluent it should constitute roughly 50% of the weight

Diluent: Microcrystalline cellulose • Microcrystalline cellulose, often referred to by the trade name Avicel, is a direct compression material. • Microcrystalline cellulose is prepared by hydrolysis of cellulose followed by spray drying • Two tablet grades of microcrystalline cellulose exist: PH 101 (Powder) & PH 102 (Granules)

Diluent: Microcrystalline cellulose • It is extremely compressible and is capable of yielding very hard tablets which at the same time disintegrate rapidly in water • It is relatively expensive when used as a diluent in high concentration and thus used in combined with other materials (lactose) • 5 to 15% concentration of microcrystalline cellulose is usually

Diluents: Manitol • Manitol is perhaps the most expensive sugar used as a tablet diluent • Manitol is used in chewable tablet as diluent because - Negative heat of solution  - Slow solubility  - Pleasant feeling in mouth • Relatively nonhygroscopic and can be used in vitamin formulation, in

Diluents: Modified Starch • Used as a diluent, binder & disintegrating agent: Sta-Rx 1500 and Celutab • Free flowing • Directly compressible • Used in chewable tablet in place of manitol because of their sweetness and smooth feeling in mouth • Contain 8 to 10% moisture & may increase hardness after

Diluents: Calcium phosphates

• The dihydrate and anhydrous form of dibasic calcium phosphate and tribasic calcium phosphate are used • They are widely used both as wet granulation and direct compression diluents in tablet formulation • Bulk density of calcium phosphates is higher than that of organic fillers

Diluents: Calcium phosphates

• They are non hygroscopic. They are used extensively in vitamin and mineral preparations • They are abrasive in nature and hence can cause wear of tablet tooling • Sometimes their alkalinity is a major source of drug instability •

Influence of diluents: Bioavailability • Although diluents are normally thought of as inert ingredients, they can significantly affect the biopharmaceutical, chemical and physical properties of tablet. • The calcium salts interfering with the absorption of tetracycline from the gastrointestinal tract. They make half the bioavailability of standard product.

Influence of diluents: Bioavailability • Antiepileptic drug sodium phenytoin will form poorly absorbable calcium-phenytoin complex, when calcium sulphate dihydrate used as diluent in the formulation. But using of lactose as diluent improves bioavailability of the antiepileptic drug significantly.

Influence of diluents: Incompatibility 

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Amine drugs + lactose (diluent)  ↓ used with Metal stearate (Mg stearate)  (Lubricant)  ↓ Discoloration of tablet with time