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SPECIAL LIPIDS

INTRODUCTION
40-50% of NCEs- sparingly soluble compounds that
require specialized formulations.
This is where the role of lipid excipients comes in play
- used as co-solvents or as carriers to protect the API
and improve its pcokinetic and pcodynamic activity.
Lipids are hydrocarbon based molecules. Thus they
are predominantly hydrophobic, but also have a
hydrophilic functional portion, such as hydroxyl,
amine, phosphate esters and carboxyl groups.
This makes lipids- a group of amphipathic molecules
that posses both hydrophobic and hydrophilic portions
to self assemble into various colloid structures in
physiological conditions.

Classification
Fatty acids
Natural oils and fats
Semi-synthetic mono-, di-, triglycerides
Semi-synthetic PEG derivatives of glycerides and
fatty acids
Polyglyceryl fatty acid esters
Phospholipids
Cholesterol
Glycolipids

Fatty Acids
A Fatty acid is a carboxylic acid with a long unbranched aliphatic chain,
which is either saturated or unsaturated. Most naturally occurring fatty
acids have a chain of an even number of carbon atoms, from 4 to 28.
Saturated Fatty acids

Stearic acid, an 18-carbon saturated fatty acid


Unsaturated fatty acid

Fatty acids having one or more double-bonds between carbon atoms .

Oleic acid, an 18-carbon monounsaturated fatty acid

STEARIC ACID

Functional Category -Emulsifying agent; solubilizing agent; tablet and capsule


lubricant

Applications in Pharmaceutical Formulation or Technology

in oral formulations as a tablet and capsule lubricant;

as a binder or in combination with shellac as a tablet coating.

It has also been suggested that stearic acid may be used in enteric tablet
coatings and as a sustained-release drug carrier

In topical formulations, stearic acid is used as an emulsifying and solubilizing


agent.

When partially neutralized with alkalis or triethanolamine, stearic acid is used in


the preparation of creams.

Incompatibilities- Stearic acid is incompatible with most metal hydroxides


and may be incompatible with bases, reducing agents, and oxidizing agents.
Ointment bases made with stearic acid may show evidence of drying out or
lumpiness due to such a reaction when compounded with zinc or calcium
salts. Stearic acid has been reported to cause pitting in the film coating of
tablets applied using an aqueous film-coating technique; the pitting was
found to be a function of the melting point of the stearic acid

SEMI-SYNTHETIC MONO-,DI- & TRIGLYCERIDES


These excipients are compatible with both soft and hard
gelatin capsules.
-Used as solubilizing vehicles,emulsifiers,suspending
agents,wetting agents and in various controlled release
dosage forms.
-Fatty acid content and composition of semi-synthetic
glycerides are more uniform than natural glycerides but
certain amount of variability can be expected.
-Variability is a funtion of excipient brand as well as
particular manufacturing lot of a given excipient.

SEMISYNTHETIC PEG DERIVATIVES

Polyethylene glycol (PEG) is a polyether compound.


PEG is also known aspolyethylene oxide (PEO)orpolyoxyethylene (POE),
depending on itsmolecular weight.
Structural formula and molecular weight of typical polyethylene glycol polymer.
GRADE

AVERAGE MOLECULAR
WEIGHT

PEG200

190-210

PEG300

285-315

PEG400

380-420

PEG600

570-613

PEG900

855-900

Parenterals

ophthalmic

Used in
biodegradable
polymeric
matrices used in
controlledrelease systems

Topical

Application
s

Aqueous
polyethylene glycol
solutions can be
used either as
suspending agents
or to adjust the
viscosity and
consistency of other
suspending
vehicles.

As Suppository Bases

Polyoxyethylene Stearates

The polyoxyethylene stearates are a series of polyethoxylated derivatives


of stearic acid.
Functional Category:Emulsifying agent

Name and molecular weight:NAME

MOLECULAR
WEIGHT

Polyoxyl 6 stearate

548.80

Polyoxyl 8 stearate

636.91

Polyoxyl 12 stearate

813.12

Polyoxyl 20 stearate

1165.55

Polyoxyl 40 stearate

2046.61

COMMERCIAL PRODUCT
COMPOUND

COMMERCIAL PRODUCT

PEG-4-distearate

Kessco200 DS (Stepan)

PEG-6-distearate

KesscoPEG 300 DS (Stepan)

PEG-12-distearate

KesscoPEG 600 DS (Stepan)

PEG-8 Stearate

Cithrol 4MS

PEG-8 Isostearate

Cithrol 4MIS

Crodas group of polyethylene glycols and polyol esters are now to be


known under the below tradenames. Polyethylene glycols and polyol esters
offer diverse properties for the formulation of a wide range of consumer
care and industrial systems.

Old Trade name

Chemical Description

New Trade name

CITHROL 10MO

PEG-20 Oleate

Cithrol 10MO

CITHROL 10MS
(VEG)
ESTOL 3751

PEG-20 Stearate

Cithrol 10MS

PEG-6 Beeswax

Cithrol 3BW

ARLACEL P135
LAN

PEG 30
Dipolyhydroxystearate

Cithrol DPHS

Polyoxyethylene Alkyl Ethers


Polyoxyethylene alkyl ethers are nonionic surfactants.

Functional Category
Emulsifying agent

Solubilizing agent

Description

Penetration enhancer

Wetting agent

They are colorless, white, cream-colored or pale yellow materials with a


slight odor. They vary considerably in their physicalappearance from
liquids, to pastes, to solid waxy substances based on m.w.

Method of Manufacture
Polyoxyethylene alkyl ethers are prepared by the condensation of
linear fatty alcohols with ethylene oxide.
The reaction is controlled so that the required ether is formed with the
polyethylene glycol of the desired molecular weight.

Commercially available grades


Name
CREMOPHOR
A25
VOLPO S2

Physical

HLB

form
Value
MICROBE 15-17
ADS
White
4.9
translucen
t
plastic wax

Application
Used as emulsifier for o/w emulsion,
creams.
Used in microemulsion gels, creams
and lotions, physical sunscreens,
lipsticks, aqueous/alcoholic
preparations, depilatories,
antiperspirants and deodorants and
shaving preparations.

New applications:

Polyoxyethylene alkyl ethers have been studied in drug delivery systems


containing oleosomes, hydrosomes, phosphosomes, vesicles and niosomes.
It is found to have an enhanced skin permeation of drugs such as ibuprofen
and clotrimazole.
Enhanced ocular absorption of insulin from eye drops, and an ocular insert device
have been observed using polyoxyethylene alkyl ethers in the formulation systems.
It shows effective enhancement in the intestinal absorption of poorly absorbed
hydrophilic compounds.

POLYGLYCERYL FATTY ACID ESTERS

Synonym : Glycerine fatty acid ester

Composition : chain of glycerol molecules ( linked together by ether


linkage) + esterified fatty acid molecules (1-2)

Eg polyglyceryl -6 dioleate is a chain of 6 glycerol molecules


esterified with 2 molecules of oleic acid .

General structure :

HLB : Hydrophilicity with in poly glycerol chain length and


no. of free OH groups , and
with no. or chain length of
esterified fatty acid.
Therefore , the hydrophilicity can range from low , approaching
that of triglycerides(polyglyceryl-6 octastearate , HLB 2.5 ) to high
(polyglyceryl-10 mono,dioleate , HLB 11 .)
Ranges from : liquid waxy
saturated unsaturated
water soluble - oil soluble compounds .
Non toxic
Biodegradable : degrades to glycerol and fatty acid in the body .
Applications : surfactant , solubilizers , vehicles ,emulsifiers and
drug crystallization inhibitor in pharmaceuticals .
Other applications : emulsifier and stabilizer in food industries ,
cosmetics soap , shampoo etc .

PHOSPHOLIPIDS

Amphiphilic molecules
Formed by phosphate grp linkage to the terminal OH grp of glycerols
COMMON HEAD Grps: choline(Phosphatidylcholine), ethanolamine
(Phosphatidylethanolamine),serine(Phosphatidylserine), etc.
Because of their amphiphilic nature, phospholipids will associate at
hydrophobic/hydrophilic interfaces
Functional Category Anionic, cationic, nonionic surfactant
biodegradable material;
dispersing agent; emulsifying agent; emulsion stabilizer;
solubilizing agent;
Applications in Pharmaceutical Formulations stabilize emulsions and suspensions
In formulations administered as lung surfactants, in intravenous fat
emulsions, and in oral solutions (e.g. Rapamune)
To form various types of liposomes eg.
1. Unilamellar
2. Multilamellar
3. Multivescicular

Examples

Common name

Trade name

manufacturer

synonym

Dilauroyl
Coatsome MCphosphatidylchol 2020PhosphoLipidine
DLAPC

NOFNippon

DLPC

Dimyristoyl
Coatsome MCphosphatidylchol 4040Lipoid PC
ine
14:0/14:0 (DMPC)
PhosphoLipidDMPC

NOFLipoid Nippon

DMPC

CHOLESTEROL
Nonproprietary Names
BP: Cholesterol
JP: Cholesterol
PhEur: Cholesterol
USP-NF: Cholesterol
Synonyms
Cholesterin; cholesterolum.
Chemical Name and CAS Registry Number
Cholest-5-en-3b-ol [57-88-5]
Empirical Formula and Molecular Weight
C27H46O 386.67
Structural Formula

Functional Category
Emollient; emulsifying agent.

Applications in Pharmaceutical Formulation or Technology

1. Cholesterol is used in cosmetics and topical pharmaceutical formulations at


concentrations of 0.35.0% w/w as an emulsifying agent.
2. It imparts water-absorbing power to an ointment and has emollient activity.
3. Cholesterol also has a physiological role. It is the major sterol of the higher
animals, and it is found in all body tissues, especially in the brain and
spinal cord.

. Incompatibilities -Cholesterol is precipitated by digitonin


. Related Substances -Lanolin; lanolin alcohols; lanolin hydrous.

REFERENCES
Handbook

of pharmaceutical excipient
Oral lipid-based formulations
Avanti polar lipids(www.avantilipids.com)