Pharmacologically active drug substances (Active pharmaceutical ingredients, API) and excipients. Medicine is a composition of drugs and excipients. The drug is API, which shows pharmacological action that can treat and cure any disease. The excipients are also known as additives that are inactive ingredients. An excipient is a substance with no therapeutic value and is an inert material added to the drug in the formulation.
It serves active pharmaceutical ingredient's technological, biopharmaceutical, and stability advancement. Excipients help in the production of medicine. It improves the patient's acceptability. It enhances the therapeutic properties of active ingredients in the final dosage form by facilitating drug absorption, reducing viscosity, and increasing solubility.
Ideal Properties of Excipients:
- Must be inert (physiologically inert).
- Non-toxic and commercially available in acceptable grade.
- Compatible with API
- Low cost
- They must be physically and chemically stable both individually and in combination with the drugs.
- They must be free from microorganisms.
- They must be Color-compatible
- They should not alter the bioavailability of drugs.
Classification of excipients:
- Diluents or filler
- Disintegrants
- Binder or Adhesive
- Lubricant
- Anti adherents
- Glidant
- Organoleptic Ingredients
- Preservatives
1. Diluents or filler:
It is also known as a filler or bulking agent. When the drug dosage is insufficient to produce the desired bulk, these are intended to be used in addition to the tablet. Generally, the active ingredient required in a single tablet ranges from 1 mg to 1000 mg. So, it is impossible to make a tablet with such a small mass; therefore, diluents are mixed with the active component. Usually, the range of diluents may vary from 5% to 80%. It is required when the drug dose is low to make up the volume. When the drug dose is sufficiently high, then excipients are not necessary. Diluents are used in tablets to improve their properties, which include:
- Improve cohesion
- To allow direct compression manufacturing to be used
- To promote flowability
- Adjust the weight of the tablet as per die capacity.
Some Examples of Diluents:
Soluble tablet diluents: Lactose (Monohydrate, anhydrous, spray dried), Sucrose, mannitol, Sorbitol
Insoluble tablet diluents: Hydrolized starch, Powdered cellulose, Microcrystalline cellulose (MCC), Calcium phosphate (dehydrate and anhydrous form).
2. Disintegrants:
These substances are added to a tablet formulation to facilitate its breaking after administration in the GIT. When disintegrants become wet, they expand and dissolve, breaking the tablet apart in the digestive tract and releasing the active ingredients so they can be absorbed. They make sure that the tablet dissolves more efficiently by breaking down quickly into smaller pieces when it comes into contact with water. Some examples of disintegrants used in tablet formulation are starch (3-25%), microcrystalline cellulose (10% w/v), and Na carboxy methyl cellulose (1-20% w/v).
Superdisintegrants: These disintegrating agents swell up to 10 folds within 30 seconds when they come in contact with water and facilitate the rapid breakdown of tables. Some examples are Croscarmellose sodium, Crospovidone, and Sodium starch glycolate.
3. Binder or Adhesive:
These substances are added to a dry-filler mixture to ensure excipients tightly bind with medicament. These agents provide proper moisture to convert fine powder into dampness, which forms granules after passing through a sieve of a suitable number. The ingredients of a tablet are kept together in a binder. It ensures the formation of tablets and granules with the necessary mechanical strength. It should be compatible with other formulation ingredients and provide the force of cohesion required for powders. Using binders cautiously is essential because their concentration can significantly affect the tablet's properties.
i. Solution binder: They are added as a powder with other excipients in wet granulation. When adding granulating fluid, the binder may dissolve partially or entirely and exhibit adhesive binding properties. Some examples are:
- Hydroxypropyl methylcellulose (HPMC)
- Starch (5-10%),
- Sucrose,
- Polyethylene glycol (PEG)
- Gelatin (5-20%)
- Acacia (5-20%) that gives very hard granules
- Polyvinyl pyrrolidine (PVP,5-20%) that are used for non-aqueous granulation.
- Tragacanth (20%) that gives hard granules.
ii. Dry binders: These are added to the powder blend after a wet granulation step or as part of a direct compression formula. For example, Microcrystalline cellulose (MCC), Cross-linked PVP, etc.
4. Lubricant:
These are used in tablet and capsule formulations. They facilitate the ejection of tablets from the die cavity. It helps to reduce the friction between the particles during compression and between the walls of the tablets and the walls of the cavity in which the tablet was formed. It forms a coat around each granule, and this effect also extends to the tablet's surface. It should be added in the final mixing step after complete granulation. It helps prevent the sticking of granules to tooling-anti adherent. Example,
- Stearate (Magnesium stearate, calcium stearate, sodium stearate)- (0.25% to 1% w/w)
- Talc (1-10%)
- Waxes (1-5%)
- Liquid paraffin (up to 5% w/w)
- Sodium benzote (5% w/w)
- Sodium lauryl sulphate (1-5%)
5. Anti adherents:
It is an anti-sticking agent that prevents the adhesion of the tablet surface to the die walls and the punches. It prevents the picking and sticking of the tablets.
Talc, Corn starch, Colloidal silica
6. Glidant:
It promotes the flow properties of granules or powder materials of tablets by reducing friction between particles. In tablet manufacture, it is added just before compression. The effects of glidant depend on the shape and size of the glidant and the granules. If excess amounts of glidant are used, it causes a decrease in the rate of flow. Talc is superior to starch that has retard effect on the disintegration-dissolution profile, so its concentration should be limited. Nowadays, silica-type glidant is
mainly used because of its small particle size. Example
- Colloidal silica (0.1-0.5% w/w) has the most common and excellent glidant properties.
- Talcum (1-10% w/w)
- Starch
- Magnesium stearate
- Silicates
- Calcium phosphate
Note: Lubricants are added to reduce friction during compression.
Antiadgerents avoid sticking to die walls and picking by punches.
Glidant improve the flow property of material or granules.
6. Organoleptic Ingredients:
The flavoring, sweetening, and coloring agents are grouped as organoleptic excipients.
i. Colorants: The coloring agents are added in dosage form to improve the product's attractiveness. It makes product identification easy (particularly for poisonous materials). It enhances the appearance, acceptability, and patient compliance. Example
- FD & C yellow 6-sunset yellow
- FD & C yellow 5- Tartrazine
- FD & C green 3- Fast Green
- FD & C blue 1- Brilliant Blue
- FD & C Blue 2 - Indigo Carmine
- FD & C red 3- Erythrosine.
- D & C red 22 – Eosin Y
ii. Flavoring agents: They help improve the product's taste by masking unpleasant tastes. In general, flavoring of liquid products requires better experience than solid pharmaceutical dosage forms. The oral solid dosage forms, like capsules and coated tablets, do not need flavoring agents in their formulation. They are added in chewable or effervescent tablets to improve acceptance. As the flavoring agents are thermolible, they cannot be added to an operation involving heat. They may be mixed with the granules before compression as alcoholic solutions. Examples are mint, orange, Vicks, ginger menthol, etc
iii. sweetening agents: These substances are added to a drug formulation to mask its bitter taste.
Natural sweeteners: Sucrose, sorbitol, mannitol, glycerine, stevia, etc
Synthetic sweetening agents: saccharin- more than 300 times sweeter than sucrose
Aspartame-200 times sweeter than sucrose
Cyclamate-carcinogenic have a bitter aftertaste effect
Advantame, neotame,sucralose, etc.
7. Preservatives:
These chemicals extend the shelf life of pharmaceutical drugs by reducing microbial attack and oxidation of excipients and active ingredients. Preservatives should be soluble, effective, stable, odorless, tasteless, non-toxic, and non-reactive. Preparation that contains water is at risk of microbial spoilage, such as solution, emulsion, suspension, topical preparation, injectables, eye drops, etc. Solid dosage forms usually don't need preservatives. For example, methyl paraben, ethyl paraben, benzoic acid,
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