The document discusses plasticizers, additives that enhance the flexibility and fluidity of polymer materials, particularly in pharmaceutical film formulations. It covers the mechanism of action, classification, ideal properties, effects on permeability and mechanical properties, and limitations associated with their use. The selection of an appropriate plasticizer is critical for optimizing coated dosage forms while balancing desired and undesired effects.

1. Plasticizers
Ahmed Shohrawar Mahadi
Department of Pharmaceutical Sciences,
North South University, Dhaka

2. Outline
Introduction
Why do we need plasticizers?
Mechanism of action of plasticizers
Properties of plasticizers
Classification of plasticizers
Selection of plasticizers
Effect of plasticizer on permeability of film.
Effect of plasticizer on mechanical properties of film.
Effect on residual internal stress.
Effect of plasticizers on release rates of drug.
Texture of plasticized films.
Limitations.
Conclusion.

3. Introduction
Plasticizers or dispersants are additives that increase the
plasticity or fluidity of a material. It is a material, usually a plastic,
makes it flexible, resilient and easier to handle.
Plasticizers are colorless, odorless liquids & relatively low
molecular weight which have a capacity to alter the physical
properties of polymer for more useful as film forming agents. It
may reduce the melt viscosity, lower temperature of
second order transition.
The function of plasticizer is to make the polymer more pliable,
soft and enhancing the flexibility, plasticity and the mobility of
the polymeric chain.
There are more than 300 different types of plasticizers
available . The most commonly used plasticizers are ester
like phthalates, adipates and trimellitates.

4. Why do we need plasticizers?
Almost all the film forming agents or polymers are brittle in
nature due to presence of multiple polymeric strands
within a single molecule . Most are the cellulose derivatives or
cellulose related compounds like HPMC, MC, EC etc.
When such a material is applied as a film coat, a smooth film is
not be obtained. Plasticizers diffuse within the polymers and cause
polymer deformation and coalescence into homogeneous films.
The effectiveness depends upon polymer compatibility and the
permanence of plasticizer during the course of shelf life.

5. Cont'd
These polymers are widely used as film forming materials as they:-
Produce transparent & intact films.
They have lower values for water vapor permeability & oxygen
transmission rate.
Physicochemical properties of the films mainly the water uptake
and erosion, solid-state crystallinity, thermal behavior and water
vapor and drug permeability are modified to a greater extend.
They can be structurally modified to achieve sustained release,
like HPMC can be converted to HPMCP for enteric coating.

6. Mechanism of action
The mechanism of action of plasticizers is defined as to interpose
between every individual strand of polymer and thereby causing
breakdown of polymer -polymer interactions & preventing them
from re-forming the chain-chain interactions
The tertiary structure of the polymer is modified into more
porous, flexible and with less cohesive structure.
Plasticizers soften and swell the polymer (latex spheres) which
aids in overcoming their resistance to deformation.
As a result the plasticized polymer would deform at a lower
tensile force as compared to without plasticizer. This enhances
the polymer -plasticizer interaction.
This effect in turn enhances the film elongation effect.

7. This interaction to a greater extend depends upon the Tg of
polymers. Glass transition temperature,(Tg) is the temperature
at which hard glassy polymer is converted into a rubbery
material.

8. 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 should be non toxic.
It should have both the hydrophilicity as well as lipophilicity.
Polar with a high Mol. Wt. ester type organic compounds.
Reduce internal friction between polymer chain.
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.
 The main role of the plasticizer is to improve mechanical properties of the
polymers by increasing flexibility, decreasing tensile strength and lowering the
second order transition temperature.

9. Classification of plasticizers
Polyols:
PEG 200-6000 grades:These are
hydrophilic & used alone as
hydrophilic plasticizers in the
conventional film coating. The
PEG with molecular weight of
6000 and above decreases
plasticizing effect and increases
lubricant effect.
Others- Glycerol, Propylene glycol.
Organic esters
Triacetin: Also known as Triethyl
glycerin or glycerol triacetate. Used
as both plasticizer and a solvent. This
plasticizer is suitable for both
aqueous and solvent based polymeric
coating of tablets, granules and beads
in concentration of 10-35% by
weight of polymer. Miscible with
water as well as in ether, ethanol,
chloroform etc.
Others - Triacetin, Diethyl phthalate
(DEP), Dibutyl phthalate (DBP) and
Tributyl citrate (TBC).
Depending on their properties they can be classified as:-

10. Cont’d
Oils/ glycerides
Castor oil, Fractionated coconut oil, Acetylated monoglycerides.
Newer Plasticizers – DBS. Under this category both the
hydrophilic as well as lipophilic esters are available.
(A) Water soluble
PEG
TEC
Triacetin
(B) Water insoluble are
DEP
DBS
DBP
ATEC –Acetyl-
triethyl-citrate.

11. Critical aspects for selection
The capacity of the plasticizer molecule to modify
the polymer-polymer interaction & the ability to solvate or
solubilize the polymer.
Should be nontoxic and compatible with other components &
should have desired stability.
Should have controlled and desired effects on the film
permeability, tackiness, flexibility, solubility, taste etc.
Plasticizer selection depends upon two major criteria:-
1)Glass transition temperature and 2)Solubility parameter.

12. Effect on permeability of films
Plasticizers play a very significant role in optimizing the
permeability characteristics of film coat to retard the entry of water
vapor and other gases .
As plasticizers modify the structure of polymers, they can alter the
diffusion or the dissolution of permeants across the polymers.
E.g.; the water absorption coefficient for HPMC films plasticized
with PEG 400 and 1000 for both the plasticizers are higher.

13. Effect of plasticizers on mechanical properties
of films.
Decrease in tensile strength
Decrease in elastic modulus
Increase in film elongation.
E.g. the effect of plasticizers on the mechanical properties of cast
film of HPMC i.e.; Methocel ES was studied and it was found
that the low molecular weight PEGs had a better plasticizing
effect as compared to higher molecular weight due to viscoelastic
effect of former.

14. Effect on residual internal stress
Plasticizers reduce internal stress within the films.
They also decrease the surface tension at the polymer
surface.
When the effect on residual internal stress of plasticizer was
evaluated on CAP films , the triacetin among the triacetin,
DEP and Citroflex 2A had the best plasticizing effect due to
lowering of residual internal stress within the films.

15. Effect of plasticizers on release rates of
drug .
Effect of plasticizer type and coat level on aqueous coating dispersions of
ethylcellulose.
To optimize the most suitable plasticizer and in its most suitable
concentration for ethylcellulose (EC).
The two commercial formulations, one Surelease/E-7-7050
containing dibutyl sebacate (DBS) and formulation 2 was Surelease/E-
7-7060 containing glyceryl tricaprylate/caprate (GTC).
The tablet was coated with 1%, 2%, 3% and 5% coat levels.
The release profile of the drug (Ibuprofen) was a function of coat
thickness.

16. Cont’d
At a coat of 2% the release of drug from with GTC plasticized
formulation appeared to follow the non-Fickian release
mechanism , whereas the tablets coated with DBS plasticized
formulation appeared to follow apparent zero-order release.
The film plasticized with GTC were intact and more elastic than
those of DBS plasticized films.
Hence it was inferred that GTC was a better plasticizer as
compared to DBS when both used in same concentrations.
The film elongation effect increase , tensile strength decreases
and glass transition temperature decreases in GTC plasticized
films.

17. Texture of plasticized films
The texture of Aquacoat films varied with the type of
plasticizers used.
Aquacoat films plasticized with DBP appeared to be more
flexible, smoother and homogeneous while those plasticized
with DEP and ATEC had raised spots and undulating
surfaces.

18. 18

19. Limitations
(A) LEACHING EFFECT-
 The major trouble encountered during the plasticizing of
polymers is the leaching of the plasticizer from the film.
This leaching effect of Plasticizer is dependent on the type and
concentration of dissolution medium. This eventually results in
drastic alteration of drug release patterns from coated dosage
forms.
Thus permanence due to leaching tendency of plasticizers can be
controlled by diffusion control.
This diffusion of plasticizer can be controlled by incorporating a
more non volatile plasticizer or switching to a higher molecular
weight plasticizer.

20. Cont’d
The molecular size and shape of the plasticizer are highly
important as small molecules migrate faster than large ones.
Also linear molecules migrate faster than bulky, branched
ones.
Permanence is an attribute taken in consideration as loss of
plasticizer during storage of plasticizers which in turn can
hamper integrity of coated tablets.
 The highly solvating ones that produce an open gel structure
migrate at a faster rate.
Volatility was found to be one of the major cause.

21. Conclusion
Plasticizers play a very significant role on mechanical
properties, permeability of films and release of drug from the
coated products.
They do enhance flexibity and plasticity of films.
Therefore, the selection of a plasticizer for a film-coating
formulation is very important in the process development
and optimization of a coated dosage form.
Curing conditions can facilitate the uniform distribution of
plasticizers.
Therefore, one needs to strike a balance between the desired
and undesired effects of the plasticizer and optimize its
concentration in the coating formulation.

22. Any Questions!!!!