|
Functional classification of excipients for tablets and other pharmaceutical products differs for diverse purposes in pharmaceutical preparation and hence may require different material attributes to achieve the desired performance.
Functions of excipients in medicinal products are: they help processing, disintegration and dissolution in the human body and assist safeguard the drug substance against unfavourable conditions, both in vivo and in vitro. They also provide bulk, so that the product can be easily picked by the patient and conveniently used.
In most cases, it is not necessary to use all of the excipients for tablets because some excipients serve two or more functions. For example, starch is a multi-functional excipient for tablets. It may serve as a diluent, binder, and disintegrating agent. Besides, the function of some excipients is not necessary for some formulations. For example, a sweetener is necessary for chewable tablets, sublingual tablets, dispersible tablets, but not for film-coated tablets.
Common excipients used for tablets
Diluents - they are essential excipients for tablets to enhance weight or volume.
Lubricants - they are vital excipients for tablets to reduce the frictional forces between particle-particle as well as particles and metal-contact surfaces.
Glidants - they promote the flow properties of tablet granules or power materials.
Colouring agent - it gives a colour or identification of the tablets as either pigment or coating materials.
Flavouring agent - it is used only in some types of tablets such as chewable tablets or dispersible tablets or in coating suspension for bad smelled tablets such as Amlodipine + Olmesartan Medoxomil tablets.
Sweetener or sweetening agent - it is especially used in the chewable, dispersible and sublingual tablets.
Release-modifying agents - they are especially used to control drug release in modified-release formulations (prolonged-release or controlled-release tablet).
Coating materials - film former which may be enteric or non-enteric; solvent; plasticizer; colourant; opaquant-extender; and miscellaneous coating solution components.
Binders - they are vital excipients for tablets to facilitate the agglomeration of powder into granules.
Classification of excipients
Standard excipients - it is either a compendial or non-compendial inactive substance. For example, lactose as a diluent and magnesium stearate as a lubricant etc. Here, compendial means the excipient is indexed in the pharmacopoeia.
Mixed excipients - it is a simple physical mixture of two or more compendial or non-compendial excipients. Mixed excipients may be either liquid or solid. For example, Opadry, Opadry II, and Eudragit (grades), etc.
Co-processed excipients - it is a combination of two or more compendial or non-compendial excipients by various methods such as granulation, melt extrusion, spray drying, milling, etc. For example, Cellactose 80 (75 per cent alpha-lactose monohydrate with 25 per cent cellulose powder), StarLac (85 per cent alpha-lactose monohydrate and 15 per cent maize starch (corn starch)) Ludipress, (combining of three excipients: lactose as carrier and filler, binding agent Kollidon 30, and disintegrants Kollidon CL).
Excipients based on their origin
Animal sources: such as lactose, stearic acid, gelatin, beeswax, and lanolin, etc.
Vegetable sources: such as starch, peppermint, guar gum, and acacia, etc.
Mineral sources: such as calcium phosphate, silica, asbestos, talc, kaolin, and paraffin, etc.
Synthetic sources: such as boric acid, lactic acid, saccharin, polysorbates, povidone, and polyethylene glycols, etc.
Disintegrants - they are essential excipients for tablets to assist dosage form’s breakup or disintegration into small units/fragments. They are vital excipients for tablets, according to USP, disintegrants are functional components that are added to formulations to promote rapid disintegration into smaller units and to allow a drug substance to dissolve more rapidly.
A disintegrant is a substance or a mixture of substances added to a tablet to facilitate its breakup or disintegration into small units/fragments and allow a drug substance to fast dissolution.
When disintegrants come in contact with water or stomach or intestinal fluid, they absorbed the liquid and start to swell, dissolve, or form gels. This causes the tablet structure to rupture and disintegrate, making increased surfaces for improved dissolution of the drug substance.
Examples of common and most used disintegrants are L-HPC (low-substituted hydroxypropyl cellulose), microcrystalline cellulose, starch pregelatinized modified, etc.
Examples of super-disintegrant are crospovidone (commercial name - Kollidon CL) [cross-linked povidone], croscarmellose sodium (trade name Ac-Di-Sol, Primellose) [cross-linked cellulose], sodium starch glycolate (commercial name Primogel, Explotab) [cross-linked starch], etc.
Some disintegrants used in pharma preparations
Crospovidone (commercial name - Kollidon CL) (2–5 per cent); Croscarmellose sodium (commercial name Ac-Di-Sol, Primellose) (10–25 per cent in capsules and 0.5–5.0 per cent in tablets) Croscarmellose sodium at concentrations up to 5 per cent w/w may be used as a tablet disintegrant. 2 per cent w/w is used in direct compressed tablets and 3 per cent w/w in wet-granulation processed tablets.)
low-substituted hydroxypropyl cellulose used in pharma preparations
Low-substituted hydroxypropyl cellulose - sodium starch glycolate (commercial name Primogel, Explotab) (2 per cent to 8 per cent, optimum or greatest degree of concentration is about 4 per cent, although two per cent is sufficient in many cases).
Chitosan hydrochloride - corn starch and pregelatinized starch; calcium alginate and calcium sodium alginate (less than 10 per cent); docusate sodium (0.5 per cent); microcrystalline cellulose (5 to 15 per cent); hydroxypropyl starch; magnesium aluminum silicate (2 to 10 per cent); Methylcellulose (2 to10 per cent); sodium alginate (2.5–10 per cent); Starch (3–25 per cent w/w); pregelatinized starch (5 to 10 per cent); calcium carboxymethylcellulose/calcium cellulose glycolate/carmellose calcium (1 to 15 per cent); powdered cellulose (5 to 20 per cent).
The following are the some of the lubricants used in pharmaceutical solid dosage form: magnesium lauryl sulphate; magnesium stearate; magnesium silicate; calcium stearate; sodium stearate; sodium lauryl sulphate; sodium stearyl fumarate; stearic acid; glyceryl behenate; behenoyl polyoxylglycerides; glyceryl monostearate; glyceryl tristearate; glyceryl dibehenate; lauric acid; myristic acid; palmitic acid; poloxamer; polyethylene glycol; polyethylene glycol 3350; polysorbate 20; polyoxyl 10 oleyl ether; polyoxyl 15 hydroxystearate; polysorbate 40; polyoxyl 20 cetostearyl ether; polyoxyl 40 stearate; polysorbate 60; polysorbate 80; potassium benzoate; sodium benzoate; sorbitan monolaurate; sorbitan monooleate; sorbitan monopalmitate; sorbitan monostearate; zinc stearate; sorbitan sesquioleate; sorbitan trioleate,etc.
Conclusion
Pharmaceutical products are rarely given as pure chemical materials only and are always administered in formulated dosage form with active pharmaceutical ingredients and inactive ingredients. These therapeutically inactive ingredients of pharmaceutical preparation are known as excipients.
Excipients can be defined as natural or synthetic inert additives used in pharmaceutical formulations. They serve many purposes such as enhancing the bulk for tableting and capsules, increasing the flow properties of the poorly flowing active pharmaceutical ingredients by performing functions such as binding, lubrication, disintegrants, low-substituted hydroxypropyl cellulose, for maintaining the pH of the liquid formulations; enhancingflow-ability, for improving compressibility, etc.
(The author is an expert in chemicals and pharmaceuticals)
|