SEMINAR
ON
PLASTICIZERS
BY
NAGARAJU .J
M.PHARM 1ST SEMESTER,
UNIVERSITY COLLEGE OF PHARMACEUTICAL SCIENCES
WARANGAL
CONTENTS





INTRODUCTION
IDEAL PROPERTIES
CLASSIFICATION OF PLASTICIZERS
MECHANISM OF PLASTICIZATION
PLASTICIZERS USED IN
SOFTGELATIN CAPSULES AND TABLETS
 EVALUATION OF PLASTICIZERS
 APPLICATIONS
 CONCLUSION
 REFERENCES
INTRODUCTION
 A plasticizer is a substance which when added to a material,
usually a plastic, makes it flexible, resilient and easier to
handle.
 They are colorless, odorless liquids produced by a simple
chemical reaction, where by molecules of water are eliminated
from petrochemical products.
 They are not just additives. They are major components that
determine the physical properties of polymer products.
DEFINITION :
 A plasticizer or softener is a substance incorporated in a
material (usually a plastic) to increase the flexibility,
workability,dispensability.
 It may reduce the melt viscosity, lower temperature of second
order transition or lower the elastic modulus of the product.
 There are more than 300 different types of plasticizers
available.The most commonly used plasticizers are ester like
phthalates, adipates and trimellitates.
IDEAL PROPERTIES OF PLASTICIZERS:
• It should be flexible resilient and easier to handle.
• It should be non volatile with high boiling point.
• It should not come out from materials to which it is added.
• Plasticizers used for internal purpose such as tablet
coating, capsule shell manufacturing should be non toxic.
• Lower the tensile strength and softening temperature, of
the polymeric materials to which it is added.
• It should reduce the brittleness, improve flow,
flexibility, and increase toughness, shear strength, and
impart resistance to the polymeric film coating.
• It should lower the glass transition temperature of the
polymeric film coating. It should reduce the viscosity
of materials to which it is added.
• it should impart permanent properties such as liability,
shock resistance, hand drop.
CLASSIFICATION OF PLASTICIZERS
These are two types
 Internal plasticizers
 External plasticizers:
 Primary plasticizers
 Secondary plasticizers
INTERNAL PLASTICIZERS:
• A rigid polymer may be internally plasticized by chemically
modifying the polymer or monomer so that flexibility polymer is
increased.
• The process by which Tg of rigid polyvinylchloride is lowered
through copolymerization, is called internal plasticization.
EXTERNAL PLASTICIZERS:
• These are high boiling liquids, non volatile and having low vapor
pressure.
• They must soluble in polymer and reduce the Tg of polymer below
room temperature rendering it softer and flexible
• They acts as lubricants between the polymer chains, facilitating
slippage of chain under stress.
PRIMARY PLASTICIZERS:
Also called as chemical plasticizers, when added to
polymer, will cause the properties of elongation and softness
of the polymer to be increased.
SECONDARY PLASTICIZERS:
Also called as plasticizing oils. They are not used
alone but when combined with primary plasticizers will
enhance the plasticizing performance of the primary
plasticizer.
TYPES OF PLASTICIZERS:
•
•
•
•
•
•
•
•
•
Phthalates
Adipates
Citrates
Phosphate esters
Polymerics
Esters of glycol and polyhydric alcohols
Sebacate nad azelate esters
Secondary plasticizers
Trimellitates
PHTHALATES:
• Both ortho-phthalic and terephthalic acids are used to react with
alcohol to produce phthalate esters
• Alcohol used in the range from methanol(c1 up to c17.)
• When added to vinyl, phthalate molecules are tightly bound up
between the long vinyl molecules, making them slip and slide
against each other without sacrificing strength.
ADVANTAGES:
• Migration is less
• Readily biodegradable
• Does not cause any harm to body.
A) DI-2-ETHYLHEXYL PHTHALATE:
• Also known as di-octyl phthalate.
• It is considered as the industry standard.
• It is phthalate ester of alcohol 2-ethylhexanol.
Advantages
• Low cost
• Posses reasonable plasticizing efficiency, fusion rate , viscosity
Disadvantages:
• It is toxic
B) DIISODECYL PHTHALATE(DIDP) AND DIISONONYL
PHTHALATE (DINP) :
•
These are prepared from oxo alcohols of carbon c9 and c10
•
These are used for heat resistant electrical cards, leather for car
interiors and PVC flooring in concentration of 25 to 50%.
ADIPATES:
•
•
•
Adipates are prepared from alcohols in the c8 to c10 range.
They are having improved low temperature performance and low
viscosity.
They are highly volatile, having high migration rate and are high
priced.
CITRATES:
• These include triethyl citrate, acetyl triethyl citrate, tributyl
citrate and acetyl tribuyl citrate
• Tri butyl citrate is heat stable and does not discolour when
processed in compound resins.
• These esters used in electrical coatings, food industry, hair
sprays and inks.
PHOSPHATES:
• They show good compatibility with PVC.
• They are having good low temperature performance, migration
resistance and improved fire retardency relative to phthalates.
POLYMERICS:
• These are produced by reacting a dibasic carboxylic acids
with one or more glycols.
• These are manufactured in a wide range of viscosities. With
increasing viscosity, handling become more difficult.
• The optimum viscosities of some acids are
adipates-5600 cps, glutarates-12000 cps.
ESTERS OF GLYCOLS AND POLYHYDRIC
ALCOHOLS:
• polyhydric alcohols are propylene glycol, glycerol,
polyethylene glycol and Esters of glycols are glyceryl
triacetate, tri ethyl citrate.
• These are water soluble and used in aqueous film coatings.
SECONDARY PLASTICIZERS:
• They are also known as extenders.
• The majority of these plasticizers include chlorinated
paraffin's, which are hydrocarbons chlorinated to a level of 3070%.
• The fire retardency and viscosity increases with chlorine
content.
• Other materials used are epoxidised soya bean oil and
epoxidised linseed oil.
• They acts as lubricants to pvc due to their epoxy content.
TRIMELLITATES:
• Common esters in these family are tris-2
ethylhexyltrimellitate,L810TM, an ester of mixed c8 and c10
linear alcohols.
Advantages:
• Low volatility
• Low migration rate.
SEBACATE AND AZELATE ESTERS:
• Di-2-ethylhexyl sebacate (DOS) and di-2-ethylhexyl azelate
(DOZ) are the most common members of this group, but
Diisodecyl Sebacate (DIDS) is also used. They give superior low
temperature performance than adipates.
GLASS TRANSITION TEMPERATURE(Tg):
• The temperature at which the glassy polymer becomes rubbery
on heating and rubbery polymer reverts to glassy on cooling is
called the glass transition temperature.
• Polymer in rubbery state are very viscous liquids with
relatively high freedom of rotation round the carbon-carbon
bonds in the backbone with in the constraint of tetrahedral
bond angle.
• The temperature is high enough so that most bonds capable of
overcoming potential energy barrier against rotation. This
rotational freedom results in very flexible chains.
GLASS TRASITION TEMPERATURE OF EUDRAGIT RS 30 D POLYMERIC FILMS
Plasticizer
pla
Tg of Eudragit RS 30D(ºc)
10% plasticizer
20%plasticizer
Triethyl citrate
34.3
12.8
Acetyl triethyl citrate
37.0
17.5
Tributyl citrate
38.5
20.5
Acetyl tributyl citrate
38.2
22.2
Triacetin
42.2
27.4
Tg of unplasticized
film is 55ºc
MECHANISM OF PLASTICIZATION:
•
Some involve detailed analysis of polarity, solubility and
interaction parameters and the thermodynamics of polymer
behavior, whilst others treat plasticization as a simple lubrication
of chains of polymer, analogous to the lubrication of metal parts
by oil.
•
The following steps are involved in the incorporation of a
plasticizer into a PVC product.
1. Plasticizer is mixed with PVC resin.
2. Plasticizer penetrates and swells the resin particles.
3.
4.
5.
Polar groups in the PVC resin are freed from each other.
Plasticizer polar groups interact with the polar groups on the
resin.
The structure of the resin is re-established, with full
retention of plasticizer.
Theories of plasticization are :


The Lubricity Theory
The Gel Theory

The Free-Volume Theory
LUBRICITY THEORY:



A “dry” polymer, a resin without plasticizer, is rigid
because friction exists between its chains, binding them
into a network.
When the polymer is heated in order to be plasticized, the
binding is weakened and the smaller plasticizer molecules
are able to slip in between the chains.
When the polymer cools, the plasticizer molecules act as a
lubricant between the chains, allowing them to “slip.”
GEL THEORY:

The plasticizer molecules break up the polymer-polymer
interaction by getting in between the chains and
“obscuring” these interaction sites from the polymer
molecules.
THE FREE VOLUME THEORY:
• The free volume of a polymer can be described as the “empty
internal space” available for the movement of the polymer
chains.The free volume of a polymer greatly increases when it
reaches the glass transition temperature.
•
At the glass transition temperature, the molecular motion
begins to occur, which corresponds to an increase in the free
volume of the polymer.
• These plasticizer molecules are having low glass transition
temperature than the polymer, so that Tg of the resulting
mixture will be lower.
PLASTICIZERS USED IN CAPSULE
MANUFACTURE
 The most common plasticizers used in manufacturing of hard and
soft gelatin capsules polyvinyl alcohols, sorbital and propylene
glycols.
 The amount and choice of the plasticizer help to detemine the
hardness of the final product, and may also affect the dissolution or
disintegration the Soft gel, as well as its physical and chemical
stability.
 The ratio of dry plasticizers to dry gelatin determines the hardness
of the shell and can vary from 0.3-1.0, for a very hard shell 1.0 to
1.8 for a very soft shell up to 5% sugar may be may be included to
give chewable quality to shell.
Typical shell hardness ratios and their uses
Hardness
Hard
Medium
Soft
Ratio of dry
Usage
glycerin/dry gelatin
0.4/1
Oral, oil based or shell
softening products and
those destined primarily
for hot, humid areas.
0.6/1
Oral tube, vaginal oil
based, water-miscible
based or shell hardening
products and those
destined primary
0.8/1
Tube, vaginal, water
miscible based or shells
hardening products and
those destined primary
for cold, dry areas.
PLASTICIZERS IN TRANSDERMAL DRUG DELIVERY
PATCHES:
•
Acrylic-acid matrices with plasticizers have been used to
make drug–polymer matrix films for transdermal delivery
systems. Some of the polymers that have been reported are
Eudragit RL PM, Eudragit RS PM, Eudragit S-100.
• Ethyl cellulose and pvp matrix films with 30% dibutyl
phthalate as a plasticizer have been fabricated to deliver
diltiazem hydrochloride and indomethacin.
• The addition of hydrophilic components such as PVP to an
insoluble film former such as ethyl cellulose tends to enhance
its release-rate constants.
PLASTICIZERS IN FILM COATING:
The commonly used plasticizers can be categorized into three groups:
1. Polyols:
(a) Glycerol (glycerin);
(b) Propylene glycol;
s(c) Polyethylene glycols PEG (generally the 200–6000 grades).
2. Organic esters:
(a) Phthalate esters (diethyl, dibutyl);
(b) Dibutyl sebacete;
(c) Citrate esters (triethyl, acetyl triethyl, acetyl tributyl);
(d) Triacetin.
 3. Oils/ glycerides:
(a) Castor oil;
(b) Acetylated monoglycerides;
(c) Fractionated coconut oil
Plasticizers used in controlled release drugs such as
Dibutyl sebacate
Diethyl phthalate
Triacetin
Triethylcitrate
Acetylated monoglyceride
 Plasticizer acts as a film forming aid by reducing the glass
transition temperature of the polymer, thereby promoting the
coalescence of the latex particle.
 The degree of plasticization of a polymer is dependent ton the
amount of plasticizer added, interactions between the polymer and
plasticizer.
EFFECT OF PLASTICIZERS ON THE MECHANICAL
PROPERTIES OF THE FILM:
 Common methods used to evaluate mechanical properties of
polymeric films include microindentor probe analysis, and shear
tests, and stress relaxation.
 The stress–strain test is probably one of the most popular and
widely used technique to determine the mechanical properties of
polymeric materials.
 Stress–strain testing generally consists of applying an axial load to
an isolated free film and measuring the load and deformation
simultaneously. The stress–strain test will provide a generalized
curve from which several useful properties can be determined .
 The basic requirements to be met by a plasticizer are
permanence and compatibility.
 Compatibility, demands that the plasticizer must be miscible
with the polymer and exhibit similar intermolecular forces to
those present within the polymer.
 Permanence is an attribute to be taken into consideration as
loss of plasticizer, It leads to the cracking of the coating under
inappropriate storage.
 Permanence is obviously related to plasticizer volatility;
however a change to a more non volatile plasticizer by
changing to a higher molecular weight plasticizer is not always
an advantageous move.
EFFECT OF PLASTICIZERS ON PERMEABILITY OF FILM
COATINGS:
water vapour transmission cell
• These water vapor transmission cells rely on a vapor pressure
gradient to achieve a linear weight gain. From the daily weight
gains, the water vapor permeability constant can be calculated
using equation
• where Perm is the moisture permeability constant, W is the amount
of moisture transmitted per unit ]time, L is the thickness of the film,
A is the area of the film exposed, and DP is the vapor pressure
gradient.
• Water vapors have been shown to permeate more rapidly through
films containing hydrophilic plasticizers, whereas the inclusion of
a hydrophobic plasticizer in the coating has been found to exert no
significant effects on water vapor permeability.
EVALUATION OF FILM PROPERTIES:
 The free films were cut into strips of 70 mm × 10 mm for
evaluation of mechanical properties or circular pieces with diameter
of 7.46 cm for determination of water vapour permeability.
 Film thickness was determined by measuring the thickness at five
scattered points on the film, using a digital micrometer (Mitutoyo,
Japan) and the values averaged.
 Only film samples with mean thickness within the range of 180 to
220 mm and thickness value variation less than 10 % in each film
were used for the above tests.
 Film samples used for mechanical testing, assay of plasticizer and
moisture content and determination of percent weight change were
stored in controlled environment chambers of 30°C and 50 or 75 %
RH.
• samples were equilibrated at ambient room condition of 22 + 2°C
and 55 +2 % RH for 1 hour prior to testing. This is to minimise
any variations in result due to room condition.
MECHANICAL PROPERTIES:
• The mechanical properties of the films were evaluated using a
tensile testing instrument (EZ Test-100N, Shimadzu, Japan)
mounted with a 100 N capacity load cell..
• Four mechanical properties, namely tensile strength, % elongation
at break, elastic modulus and work of failure were computed from
the load - strain profile, and film dimensions as shown below.
• t = Lmax/Ai
• e= ∆lb/li
• EM =dL/dm/Ai
• ω = AUC x δ/Ai
(1)
(2)
( 3)
(4)
PLASTICIZER CONTENT:
• The amount of plasticizer in the Aquacoat film was determined
using gas chromatography (Model 5890 series II Hewlett
Packard) with a split/ splitless inlet, a 23.5 m by 0.32 mm
fused silica-polyethylene glycol capillary column (HP-FFAP
X-linked polyethylene glycol) and a flame ionization detector.
• About 200 mg of film sample were accurately weighed and
dissolved in methanol. An internal standard of 1 ml was then
added to the mixture. triethyl citrate (TEC) (5 mM) was
employed as the internal standard for GTA while glycerin
triacetate (GTA) (10 mM) solution was the internal standard
for the rest of the plasticizers.
• Using methanol, the mixture was made up to a final volume of
20 ml for dibutyl phthalate (DBP) and 10 ml for the rest.
Nitrogen was used as the carrier gas at a flow rate of 28.5
ml/min, with injector temperature at 240°C and detector
temperature at 270°C.
• For the assay of DEP, TEC, ATEC and GTA, the column
temperature was increased from 150°C to 230°C at a rate of
10°C/min and held at 230°C for 3 min.
•
For the assay of DBP and acetyltriethyl citrate (ATEC) , the
column was heated up from 150°C to 240°C at a rate of
10°C/min and held at 240°C for 5 min
APPLICATIONS:
 The plasticized PVC is used for life saving medical devices
such as medical tubing and blood bags,t o footwear, electrical
cables ; packaging, stationary, and toys.
 Phthalates are used in other non pvc applications such as
paints, rubber products, adhesives and some cosmetics.
 The butyl benzyl phthalate- plasticized polymeric material has
consumer and industrial uses such as flooring, sealants and
coatings
PHARMACEUTICAL APPLICATIONS
 Used in functional and nonfunctional coating of solid dosage
forms, including tablets, beads and granules, such as film
coating, enteric coating, osmotic tablet coatings etc. to impart
flexibility to the different types of coating materials.
 In the production of soft gelatin capsules.
 In the manufacture of life saving medical devises such as
• IV administration
• Dialysis
• Cardio-pulmonary bypass (CPB) procedures
 Bags used to store and transport:
• Enteral nutrition formulae
• Total parenteral nutrition formulae
 Tubings used in enteral nutrition:
Nasogastric tubes
Nasojejunal tubes
 Also used in manufacturing of transdermal patches
CONCLUSION:
 Plasticizers are necessary for almost all polymers that are
currently used for film coating of tablets and beads.
Plasticizers reduce the brittleness, improves flow, impart
flexibility, and increase flexibility, and increase toughness,
strength, tear resistance of polymers.
 Although there are many plasticizers used in chemical
industry, only a few plasticizers have been approved for
pharmaceutical applications due to environmental and human
health concerns attributed to plasticizers toxicity.
REFERENCES:
1. D.F and Howick, C.J., "Plasticizers", Encyclopaedia of
Chemical Technology, 4(19): 258-290(1996).
2.Porter S.“Coating of Pharmaceutical Dosage forms”,
Remington's book of science, 1: 894-902.
3. “Encyclopedia of pharmaceutical technology” by James
Swarbrick, 1734, volume-3.
4. Sakellariou, P., Rowe, R. C., and White, E. F., Int. J.
Pharm., 31: 55 (1986).
5. Entwistle, C. A. and Rowe, R. C., J. Pharm • Pharmacol.
31: 269(1979)
6. Porter, S. C., Pharm • Tech., 4(3): 66 (1980).
7. Aulton, M. E., Twitchell, A. M., and Hogan, J. E.,
Proceedings of AGPI Conference, Paris (1986).
8.Crawford, R. R. and Esmerian, O. K., J. Pharm. set.
60(2):312 (1971).
9. Entwistle, C. A. and Rowe, R. C., J. Pharm •
Pharmacology. 31: 269(1979) .
10. Skultety, P.F. & Sims, S. Drug Dev. Ind. Pharm. 13:2209–
2219 (1987)
11. Aulton, M.E., Abdul- Razzak, M.H. & Hogan, J.E. Drug
Dev. Ind. Pharm. 7:649–648. (1981)
THAN’Q’