Pharmaceutical Excipients

Pharmaceutical Excipients

“Pharmaceutical excipients are substances other than the active pharmaceutical ingredient (API) that have been appropriately evaluated for safety and are intentionally included in a drug delivery system.”

“The word excipient is derived from the Latin excipere, meaning ‘to except’, which is simply explained as ‘other than‘. Pharmaceutical excipients are basically everything other than the active pharmaceutical ingredient. Ideally, excipients should be inert.

Simply said the excipients enable the drug substance to be applied to the patient in the right form and supports the way and place of action without being active themselves.

Antioxidants
Such materials, when added to a product, prevent the active from degrading in the presence of oxygen or peroxides.

Example;-

Butylated Hydroxyanisole (BHA)
Butylated Hydroxytoluene (BHT)
Citric acid
Sodium Metabisulfite

Binders
These can be incorporated into a formulation either as a wet material, such as a starch paste or povidone solution, for wet granulation processes, or as a dry powder, such as microcrystalline cellulose, for direct compression or dry granulation processes

Example;-

Alginic Acid
Sodium alginate
Carboxymethyl cellulose sodium (CMC)
Microcrystalline cellulose (MCC)
Powdered cellulose
Confectioner’s sugar
Dextrin
Dextrose
Ethylcellulose
Guar gum
Hydroxypropyl cellulose (HPC)
Hypromellose (HPMC)
Lactose
Maltodextrin
Methylcellulose
Povidone
Starch
Tragacanth
Zein

Coating Agents
Similar to taste masking technology, the first coatings were solutions of sucrose (12–20%). Once polymers were discovered and understood, they were applied in low concentrations (1–3%) using organic solvents. Current technology uses polymers manufactured as latex or pseudo-latex dispersions to avoid the use of organic solvents. Depending on the application, aesthetic or functional coating, the use levels can range from 2 to 20% of the weight of the material being coated.

Example;-

Carboxymethyl cellulose sodium (CMC)
Carnauba Wax
Cellulose acetate phthalate (CAP)
Ethylcellulose
Gelatin
Hydroxypropyl cellulose (HPC)
Hypromellose (HPMC)
Maltodextrin
Methylcellulose
Starch
Sucrose
Zein

Colors and Pigments
There are two basic types of coloring agents for pharmaceutical products: dyes and lakes. Dyes are soluble forms of a particular color. They go into solution and can result in very deep, vibrant colors. Lakes are dyes that undergo a processing step that adheres them onto insoluble substrates, such as aluminum or calcium salts. Dyes are usually used in liquid products, whereas lakes are used in chewable products and coating solutions for tablets.

Diluents/Fillers ;-
When considering solid dosage forms, such as tablets and capsules, these ingredients function as a bulking agent for low dose actives, facilitating compression or encapsulation. Diluents are also used in lyophilized products, serving the same purpose of providing bulk to the product, but might be different materials.

Example ;-

Calcium carbonate
Calcium sulfate
Microcrystalline cellulose (MCC)
Powdered cellulose
Dextrates
Dextrin
Dextrose
Kaolin
Lactose
Maltodextrin
Mannitol
Starch
Sucrose

Disintegrants
These materials facilitate the breakdown of oral solid dosage forms in the gastrointestinal tract. Tablets and capsules must breakdown from their original form to large particles and then to small particles, increasing surface area from which drug can dissolve. Early disintegrants included different types of starch, as a dry addition to a formulation, due to the ability of the starch to swell. Significant improvement in disintegrant performance was achieved with the introduction of the first superdisintegrant, sodium starch glycolate. There are also newer, polymeric disintegrants, such as croscarmellose sodium. These super-disintegrants exhibit significantly superior swelling and water wicking capability, compared to starch, and can be used at much lower concentrations

Examples ;-

Alginic Acid
Sodium alginate
Microcrystalline cellulose (MCC)
Croscarmellose sodium
Crospovidone
Guar gum
Polyacrilin Potassium
Sodium Starch Glycolate

Emollients
These materials are usually used in conjunction with emulsifying agents in the preparation of topical products. An emollient is intended to impart a soft, supple feeling to the skin, helping the skin to retain moisture and natural flexibility.

Examples ;-

Glycerin
Glyceryl monostearate
Isopropyl Myristate
Petrolatum
Polyethylene Glycols

Emulsifiers
These materials typically exhibit some surfactant characteristics but also facilitate micelle formation, which allows for stable uniform products consisting of oil-in-water or water-in-oil biphasic emulsions or tri-phasic emulsions.

Exampels ;-

Carbomer
Carrageenan
Lanolin
Lecithin
Mineral Oil
Oleic Acid
Oleyl alcohol
Pectin
Poloxamer
Polyoxyethylene Sorbitan Fatty Acid Esters
Sorbitan Esters
Triethanolamine

Flavors
These materials were originally natural products; however, many companies have been created to develop synthetic versions of different flavors. Most manufacturers of finished products provide these Flavor Houses with samples of in-process material for flavoring. By using a Flavor House, unique flavor notes can be imparted to the product that will facilitate brand recognition.

Glidants/Antiadherents
These products facilitate the movement of the powder or granulation prior to compaction, compression, or encapsulation. Some of these materials possess moisture scavenging capabilities similar to desiccants. By facilitating flow of the material, there is less weight variability of the dosage form, resulting in more consistent dosing of the active ingredient(s). Additionally, by controlling the amount of moisture available to interact with the active ingredient(s) and other excipients, the product’s stability is enhanced

Example;-

Colloidal silicon dioxide
Talc

Humectants
These materials promote the retention of moisture. They are necessary in some semi-solid products (creams and gels) to prevent the dosage form from drying out. They also help prevent a phenomenon known as cap-locking. Cap-locking involves liquid products that recrystallized at the bottle-cap interface and makes opening the bottle difficult after prolonged periods of non-use. These materials are hygroscopic and should be stored in well closed containers prior to use.

Example;-

Glycerin
Propylene Glycol
Sorbitol
Triethanolamine

Lubricants
These materials facilitate compression/compaction of tablets and consolidation of capsule plugs. Lubricants are used in small quantities in the formulation. One could think of a particle of lubricant as a deck of cards. When the deck is undisturbed, it has a very small coverage area; however, when the individual cards are randomly tossed on a table the coverage area is greatly increased. That is how lubricants, like Magnesium, stearate function. Other lubricants, such as Stearic acid, melt during compaction/compression and exert their lubricant effects in that manner. Many lubricants are hydrophobic—water repellent. If used at too high a concentration or blended for too long, tablet hardness and/or dissolution could be negatively affected.

Example;-

Calcium stearate
Glyceryl monostearate
Isopropyl Myristate
Magnesium stearate
Polyvinyl Alcohol
Sodium Stearyl Fumarate
Stearic Acid
Talc

Preservatives
If these materials prevent the initiation and growth of microorganisms in products, they are known as bactericidal preservatives. Some preservatives, either by concentration or activity, may only maintain the bacteria level in the product at the time of manufacture and are referred to as bacteriostatic preservatives

Examples;-

Alcohol
Benzalkonium chloride
Boric acid
Butylated Hydroxyanisole (BHA)
Butylated Hydroxytoluene (BHT)
Butylparaben
Methylparaen
Phenol
Phenethyl Alcohol
Potassium Sorbate
Propylene Glycol
Propylparaben
Sorbic Acid

Propellants
These materials are found exclusively in aerosolized delivery systems. Early propellants were CFCs—chlorinated fluoro-carbons— now many non-CFC products have reached the market and are known as HFCs.

Example;-

Difluoroethane
Nitrogen

Protective Colloids
These materials are added to suspensions to protect the suspending agent and other colloidal sized particles from settling. These work in conjunction with the suspending agents or viscosifiers.

Examples;-

Hydroxypropyl cellulose (HPC)
Hypromellose (HPMC)
Methylcellulose

Sialagogues
These materials are usually acidic, and their purpose in a formulation is to stimulate the production of saliva. They are mostly found in chewable products for children or in gum-based products. By facilitating the production of saliva, the masticated product is swallowed more readily, limiting the objectionable flavor of the active from lingering too long.

Examples;-

Citric acid
Fumaric acid
Tartaric acid

Surfa ctants
Surfactants function by decreasing the surface tension of a material, coating agent, and a substrate, a tablet. By reducing the surface tension, the coating can more uniformly cover the tablet surface, resulting in a more aesthetically pleasing product. When used in suspension, the surfactant facilitates the wetting of the drug particle, facilitating its ability to go into solution.

Excipients;-

Polyethylene Glycols
Polyoxyethylene Sorbitan Fatty Acid Esters
Sodium Lauryl Sulfate
Sorbitan Esters

Suspending Agents
Suspending agents are similar to viscosifiers in a formulation. They function by keeping small particles of active, and possibly other excipients, suspended during the shelf life of the product.

Excipients;-

Acacia
Agar
Carbomer
Carboxymethyl cellulose sodium (CMC)
Carrageenan
Microcrystalline cellulose and Sodium Carboxymethyl
cellulose Co-processed
Colloidal silicon dioxide
Dextrin
Guar gum
Hydroxypropyl cellulose (HPC)
Hypromellose (HPMC)
Methylcellulose
Pectin
Polyvinyl Alcohol
Povidone
Tragacanth
Kaolin

Sweeteners
Sweeteners are materials used in both solid and liquid dosage forms that impart sweetness to the product. Sucrose is the standard against which all sweeteners, both natural and artificial, are measured. In addition to being many more times sweeter than sucrose, artificial sweeteners have the advantage of not impacting blood sugars of diabetic or pre-diabetic patients, and they are considered non-cariogenic.

Excipients;-

Acesulfame Potassium
Aspartame
Confectioner’s sugar
Dextrates
Dextrose
Fructose
Mannitol
Saccharin
Sorbitol
Sucralose
Sucrose
Xylitol

Taste-Masking Agents
The original taste maskers were very high concentrations of sweeteners. The next generation of taste-masking technology involved polymers that coated particles of active ingredients. Newer taste-masking technology involves enveloping/cloaking polymers that hide the particle of active from the taste buds.

Excipients;-

Confectioner’s sugar
Polyacrilin Potassium
Poloxamer

Viscosifiers
Viscosifiers (thickening agents) are similar in function to suspending agents; both impart thickness to liquid products. Some viscosifiers go into solution, such as certain cellulose based polymers, resulting in a Newtonian type viscosity. Other materials increase viscosity, while imparting a yield stress to the suspension. This type of product is known as thixotrope.

Excipients;-