Factor Affecting The Selection Of Exepients.

BY-SNIGDHA SHUKLAM.PHARM (1ST YEAR)

FACTOR AFFECTING EXEPIENTS

FLAVOURING AGENTS

COLORING AGENTS

DILUTENTS

DISINTIGRENTS

BINDER

LUBRICANTS

GLIDENTS

BUFFERS

SWEETNING AGENTS

HUMECTENTS

EXCIPIENTS

An excipient is an inactive substance used as a carrier for the active ingredients of a  medication.

In many cases, an "active" substance (such as aspirin) may not be easily administered and absorbed by the human body

Example: Binders, Disintegrants, Diluents, Flavours,

INTRODUCTION:

TYPES OF EXCIPIENTS

AntiadhereUSED to reduce the adhesion bet

ween the powder (gran

ules)

BindersBinders hold the ingredients in a tablet together

Coatingstablet ingredients

from deterioration by moisture

Disintegrantsdissolve when

wet causing the tablet to break

apart

Fillers and diluents

fill out the size of a tablet

Flavorsused to mask unpleasant

tasting active ingredients

Colors improve the

appearance of a formulation

Glidantspromote powder flow by reducing

interparticle friction

LubricantsPrevent ingredients

from clumping together and from

sticking to the tablet punches

PreservativesPRESERVE THE FORMULATION

Excipients – an overview● Drug products contain both drug substance (commonly

referred to as active pharmaceutical ingredient or API) and excipients.

● The resultant biological, chemical and physical properties of the drug product are directly affected by the excipients chosen, their concentration and interactions with the API

● Excipients are sub-divided into various functional classifications, depending on the role that they are intended to play in the resultant formulation.

● Certain excipients can have different functional roles in different formulation types,e.g. lactose; widely used as:

● Furthermore, individual excipients can have different grades, types and sources depending on those different functional roles….

Diluents (Fillers)● Bulking agent

◦ E.g. to make a tablet weight practical for the patient: minimum tablet weight is typically ~50mg.

● Compression aid◦ Deforms and/or fragments readily to facilitate robust

bonding in tablet compacts, e.g. microcrystalline cellulose.

● Good bulk powder flow….diluents have a strong influence

● Favoured combinations: Lactose is an excellent choice of filler in many respects but can exhibit poor flow characteristics

Disintegrants● As an aid to de-aggregation of solid

dosage forms. Disintegrants cause rapid break up (disintegration) of solid dosage forms upon exposure to moisture.

● Generally, disintegration is viewed as the first stage in the dissolution process, although dissolution does occur simultaneously with disintegration.

Binders● Binders act as an adhesive to ‘bind

together’ powders, granules and tablets to result in the necessary mechanical strength.◦ Water is the most common granulating fluid, very occasionally

in a co-solvent system with, e.g. ethanol.● Examples:

◦ Dry binders: Microcrystalline cellulose, cross-linked PVP

◦ Solution binders: HPMC, PVP◦ Soluble in water/ethanol mix: PVP

LubricantsCompression lubricants prevent adherence of granule/powder to punch die/faces and promote smooth ejection from the die after compaction:

EX:

Magnesium stearate is by far the most extensively used tableting lubricant

There are alternatives, e.g. stearic acid, sodium stearyl fumarate, sodium behenate

GlidantsMost commonly; colloidal silicon dioxide

(traditionally, talc was used)● Good bulk powder flowability is especially

important during high speed processing● Glidants improve flow by adhering to

particles and so reducing inter-particulate friction

● Very low bulk density (0.03 – 0.04g/cm3)

Excipients For Solution/Suspension Products

Again, excipients are sub-divided into various functional

classifications, depending on the role that they play in

the resultant formulation….

Solvents/Co-Solvents● Water is the solvent most widely used as a vehicle

due to:◦ Lack of toxicity, physiological compatibility, and good solubilising power

(high dielectric constant), but ⚫Likely to cause instability of hydrolytically unstable drugs⚫Good vehicle for microbial growth

● Sorbitol, dextrose, etc. are often added as solubilisers, as well as base sweeteners

● Water-miscible co-solvents are used to:◦ Enhance solubility, taste, anti-microbial effectiveness or stability◦ Reduce dose volume (e.g. oral, injections)◦ Examples: propylene glycol, glycerol, ethanol, low molecular weight

PEGs● Water-immiscible co-solvents, e.g.

◦ Emulsions / microemulsions using fractionated coconut oils

Buffering Agents● Can be necessary to maintain pH of the formulation

to:◦Ensure physiological compatibility◦Maintaining/optimising chemical stability◦Maintaining/optimising anti-microbial

effectiveness◦Optimise solubility (or insolubility if taste is

an issue)

Anti-microbial PreservativesPreservatives are used in ● multi-use cosmetic/pharmaceutical products● Ideally targeted for microbial cells - showing no toxicity/irritancy

towards mammalian cells● There are a limited number of approved preservatives available for

multi-use oral products, and options are even more limited for other routes of administration

● This restricted number can be further reduced by consideration of factors such as levels required (dose), pH-solubility profiles, API & excipient incompatibilities, adsorption, irritancy and toxicity.

Anti-Oxidants● Used to control oxidation of:

◦ API◦ Preservative, e.g. potassium sorbate◦ Vehicle, e.g. oils or fats susceptible to β-oxidation (rancidification)◦ Colourants (ageing discolouration)

● Sacrificial (more oxidisable than API, preservative, etc). Levels will reduce with time…. need to be monitored by specific assay◦ Light exposure and metal ion impurities can accelerate oxidative

degradation and hence depletion of antioxidant● Need to assess regulatory acceptability (differs in different

countries)● Efficacy can be affected by:

◦ Compatibility with other excipients◦ Partitioning into micelles (from surfactants)

Sweetening Agents Natural sweeteners

◦ Sucrose; ◦ Sorbitol

Artificial sweeteners◦ Can impart a bitter or metallic after-taste (hence used in combination

with natural sweeteners), e.g.⚫Saccharin, and it’s salts⚫Aspartame⚫Acesulfame –K⚫Sucralose – excellent sweetness, non-cariogenic, low calorie, wide & growing

regulatory acceptability but relatively expensive

Humectants● Hygroscopic excipients used at ~5% in aqueous

suspensions and emulsions for external application.

● Their function is to retard evaporation of aqueous vehicle of dosage form:◦ To prevent drying of the product after application to the skin◦ To prevent drying of product from the container after first

opening◦ To prevent cap-locking caused by condensation onto neck of

container-closure of a container after first opening

Examples include: ◦ propylene glycol◦ glycerol ◦ PEG