Active Pharmaceutical ingredient excipients

Capsule shell excipients

Excipients for capsule manufacturing usually include products designed to make the capsule easier to
administer or manufacture. Such excipients include diluents, lubricants, disintegrants, glidants and
wetting agents.

Liquid-filled hard capsules (LFHCs) are typically composed of a shell of gelatin or hydroxypropyl
methylcellulose (HPMC) and filled with compatible liquids or compositions that can flow below 70 oC.
LFHC technology offers several advantages over other solid dosage forms (1). It is crucial, however, to
select excipients that are compatible with capsule shell integrity and suitable for the purpose of a
formulation.

The capsule shell which is made of with gelatin is called gelatin capsule shell. There are two types of
capsule. One is hard shelled capsule and another is soft gelatin capsule. Both of those are made of
gelling agents like plant protein or animal protein. Plant protein is called cellulose or starch. On the
other hand, animal protein is called gelatin (mainly).
Though packaging of capsule is the major parts of the systemic step for the formulation, but gelatin
capsule sell is not primary packaging material. Packaging material has the advantages to preserve the
integrity of capsule (adequately). Packaging materials has the protective needs along with chemical and
physical characteristics. Loss of product quality or product stability depends on primary packaging
materials. Packaging materials may be glass, plastic, metal etc.
Excipients have a major role of the formulation of a dosage form. These are called the ingredients that
create the dosage form. Protective agents or bulking agents are called excipients. Excipients have
different usages and various activities. Excipients have the safety evaluation parameters.
Gelatin capsule shell is an excipient. Some characteristics of gelatin capsule shell are: these are not
reactive but chemically stable, low equipment but process sensitive, obviously inert to human body but
not toxic, having a tendency for the reactions with drug particles, having the power of excepient-
excipient or drug-excipient correlation. Moreover, these are economical.
Gelatin capsule shell is the excipient that is in great quantity. It has the drug-excipient interaction. It has
the great role for the formation of molecular complexes. It has the power of chemical degradation.
Biopharmaceutical interaction, Chemical interaction and physical interaction are the main features of
gelatin capsule shell. Dosage uniformity, rate of dissolution etc are maintained by the physical
interaction of gelatin capsule shell. These are not involved in chemical even also molecular structure
changes. These may be detrimental or beneficial that depends on their application.
Gelatin capsule shell has the impact between body fluids and medicine that influences the rate of
absorption. It has the absorption, dissolution etc. properties. It does not fail to give any kind of desired
outputs. The properties of the excipient of gelatin capsule shell are well developed. It has favorable
attributes. It is as supplementing as the newest one. The excipient of gelatin capsule shell has
multifunctional properties. Undesirable properties may be masked by this excipient. It can absorb water
quickly not only that but also rapid result of dispersion.
As excipient, there are some advantages of gelatin capsule shell:
· Super easy to handle
· Painless to carry
· Physical appearances are nice
· This is not only tasteless but also odorless
· Economic
Now it is clear that the capsule shell which is made of gelatin is not a primary packaging material.
Gelatin capsule shell is one of the most effective excipients

(https://www.americanpharmaceuticalreview.com/pfu/7964385/soids/1402571/Excipient_Search/Caps
ule)

(http://druginformationresources.blogspot.com/2014/04/gelatin-capsule-shell-is-excipient-or.html)

Binder excipients

Binder excipients are formulated to act as an adhesive to literally “bind together” powders, granules and
other dry ingredients to impart to the product the necessary mechanical strength. Commonly used in
wet granulation, binders are added to create a more effective and predictable granule formation.
Binders hold the ingredients in a tablet together. Binders ensure that tablets and granules can be
formed with required mechanical strength, and give volume to low active dose tablets. Binders are
usually:

Binders such as pregelatinized starch, microcrystalline cellulose, and various polymers are included to
facilitate the granulation step. Binders hold the granules together, making the powders easier to
compress.

Solution binders are dissolved in a solvent (for example water or alcohol can be used in wet granulation
processes). Examples include gelatin, cellulose, cellulose derivatives, polyvinylpyrrolidone, starch,
sucrose and polyethylene glycol.
Dry binders are added to the powder blend, either after a wet granulation step, or as part of a direct
powder compression (DC) formula. Examples include cellulose, methyl cellulose, polyvinylpyrrolidone
and polyethylene glycol.

(https://en.m.wikipedia.org/wiki/Excipient)
(
http://www.pharmtech.com/excipients-formulation-success)
(https://www.americanpharmaceuticalreview.com/pfu/7964385/soids/1402525/Excipient_Search/Bind
er)

Lubricant excipients
Compression lubricants prevent adherence of granule/powder to punch die/faces and promote smooth
ejection from the die after compaction. Lubricants can also be used when compression isn’t involved
such as in powder blends for filling into capsules to prevent adherence of granule/powder to equipment
surfaces and dosator mechanisms and coating the surface of multi-particulate dosage forms to inhibit
agglomeration of individual particles.

Lubricants prevent ingredients from clumping together and from sticking to the tablet punches or
capsule filling machine. Lubricants also ensure that tablet formation and ejection can occur with low
friction between the solid and die wall.
Common minerals like talc or silica, and fats, e.g. vegetable stearin, magnesium stearate or stearic acid
are the most frequently used lubricants in tablets or hard gelatin capsules. Lubricants are agents added
in small quantities to tablet and capsule formulations to improve certain processing characteristics.

There are three roles identified with lubricants as follows:

True lubricant role:

To decrease friction at the interface between a tablet’s surface and the die wall during ejection and
reduce wear on punches & dies.
Anti-adherent role:
Prevent sticking to punch faces or in the case of encapsulation, lubricants
Prevent sticking to machine dosators, tamping pins, etc.
Glidant role:
Enhance product flow by reducing interparticulate friction.
There are two major types of lubricants:

Hydrophilic
Generally poor lubricants, no glidant or anti-adherent properties.
Hydrophobic
Most widely used lubricants in use today are of the hydrophobic category. Hydrophobic lubricants are
generally good lubricants and are usually effective at relatively low concentrations. Many also have both
anti- adherent and glidant properties. For these reasons, hydrophobic lubricants are used much more
frequently than hydrophilic compounds. Examples include magnesium stearate.
(https://www.americanpharmaceuticalreview.com/pfu/7964385/soids/1402531/Excipient_Search/Lubri
cant)

Seeetener excipients
Sweeteners are added to drug formulations to
mask undesirable tastes and to promote better
patient compliance.

Sweeteners are added to make the ingredients

more palatable, especially in chewable tablets
such as antacid or liquids like cough syrup.
Sugar can be used to mask unpleasant tastes
or smells.
There are a multitude of sweeteners available
to the pharmaceutical scientist. Sweeteners
may be broadly grouped into two categories –
nutritive and non-nutritive. Nutritive
sweeteners deliver calories and as their name
suggests, non-nutritive do not. Non-nutritive
sweeteners can be further characterized as
bulk (sugar alcohols) and high intensity
(artificial).
Some excipients that are sweet are often incorrectly listed in publications as “sweeteners.” These are
excipients used primarily for purposes other than imparting sweetness, for example, co-solvents such as
glycerol or propylene glycol, and bulking agents such as lactose or maltodextrin.
(https://www.americanpharmaceuticalreview.com/pfu/7964385/soids/1402486/Excipient_Search/Swe
etener)

(https://www.pharma-excipients.ch/2018/07/23/what-are-sweeteners-an-introduction-to-
pharmaceutical-sweetener-excipients/)
Disintegrantmexcipient

Disintegrants are added to oral solid dosage forms to aid in their deaggregation. Disintegrants are
formulated to cause a rapid break-up of solids dosage forms when they come into contact with
moisture. Disintegration is typically viewed as the first step in the dissolution process.

Disintegrants expand and dissolve when wet causing the tablet to break apart in the digestive tract,
releasing the active ingredients for absorption.

They ensure that when the tablet is in contact with water, it rapidly breaks down into smaller fragments,
facilitating dissolution.

(https://www.americanpharmaceuticalreview.com/pfu/7964385/soids/1402530/Excipient_Search/Disin
tegrant)

Coating system excipients

Coatings are added to tablets to help make large, difficult to swallow pills easier to take. They also
prevent deterioration from water and moisture. Coatings can also allow for breakdown in a specific
organ in the body. For example enteric coatings allows for breakdown in the small intestine, preventing
breakdown in the acidic environment of the stomach.

Tablet coatings protect tablet ingredients from deterioration by moisture in the air and make large or
unpleasant-tasting tablets easier to swallow. For most coated tablets, a cellulose ether hydroxypropyl
methylcellulose (HPMC) film coating is used which is free of sugar and potential allergens. Occasionally,
other coating materials are used, for example synthetic polymers, shellac, corn protein zein or other
polysaccharides. Capsules are coated with gelatin.

Enterics control the rate of drug release and determine where the drug will be released in the digestive
tract. Materials used for enteric coatings include fatty acids, waxes, shellac, plastics, and plant fibers.

(https://www.americanpharmaceuticalreview.com/pfu/7964385/soids/1402487/Excipient_Search/Coati
ng_Systems)

pH modifier excipients
pH modifier excipients are used in the pharmaceutical industry due to their antioxidant properties. pH
modifiers can help maintain the stability of pharmaceutical and can also be used as preservatives.

In cases where it is necessary to control the pH of the local environment, pH modifiers such as citric acid
or sodium acetate can be added. These agents can help if solubility or stability is better in a certain pH
range, he explains. Wetting agents such as polysorbates or sodium lauryl sulfate can be added to help
wet the API and get it into solution faster.

(https://www.americanpharmaceuticalreview.com/pfu/7964385/soids/1402490/Excipient_Search/pH_
Modifier)

Preservative excipients

Preservatives are included in pharmaceutical dosage forms to control the microbial bioburden of the
formulation. The activity of a preservative is dependent on the correct form of the preservative being
available in the formulation at the required concentration to inhibit microbial growth.

Some typical preservatives used in pharmaceutical formulations are

Antioxidants like vitamin A, vitamin E, vitamin C, retinyl palmitate, and selenium

The amino acids cysteine and methionine
Citric acid and sodium citrate
Synthetic preservatives like the parabens: methyl paraben and propyl paraben.
Filller excipients

(https://www.americanpharmaceuticalreview.com/pfu/7964385/soids/1402485/Excipient_Search/Pres
ervative)

Plasticizer excipients

Plasticizers are used mainly for oral solid dosage forms. Plasticizers are added to the polymers used as
film forming agents in order to make the polymer pliable and soft, enhancing the flexibility and plasticity
of the films. They are added to these products to reduce the glass transition temperature facilitating the
thermal stability of the drug and other ingredients.

The plasticizing process aims at two primary targets:

It reduces the glass transition temperature of the film forming polymer to allow the coating process to
take place at reasonable temperatures.

It prevents cracks in and consequent peel-off of the film during storage, which would harm both its
functionality and its appeal to the patient.
(https://www.americanpharmaceuticalreview.com/pfu/7964385/soids/1402527/Excipient_Search/Plast
icizer)
(https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-
science/excipient)

(https://pharmaceutical.basf.com/en/Drug-Formulation/Instant-Modified-Release/Plasticizers.html)

Surfactant excipients
The functional role of surfactants in pharmaceutical preparations include: modulating solubility and
bioavailability of APIs; increasing the stability of active ingredients in the dosage forms; helping active
ingredients to maintain preferred polymorphic forms; maintaining the pH and/or osmolality of liquid
formulations; acting as antioxidants, emulsifying agents, aerosol propellants, tablet binders, and
disintegrants; preventing aggregation or dissociation; and modulating immunogenic responses of active
ingredients.

(https://www.slideshare.net/nahidhasan7921/pharmaceutical-excipients)

(https://www.americanpharmaceuticalreview.com/pfu/7964385/soids/1402494/Excipient_Search/Surfa
ctant)