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Film coating agent
Aug 02, 2018

SUMMARY

The chapter commences by reviewing the properties of the broad classes of materials used in film
coating, polymers, plasticizers, pigments and solvents (or vehicles).
An initial consideration of the polymers shows that while processing is most commonly performed
using these materials in solution, there are systems which utilize polymers in suspension in water. The
mechanism of coalescence and film formation for these types of materials are discussed.
The individual polymers are dealt with in some detail and an attempt is made to divide them into
functional and non-functional coating polymers. Functional polymers being defined as those which
modify the pharmaceutical function of the compressed tablet, for instance an enteric or modified releae
film. However, this distinction is sometimes blurred as one coating polymer can fall into both groups.
The essential polymer characteristics of solubility, solution viscosity, film permeability and mechanical
properties are described in terms of ultimate film requirements.
In the treatment and description of plasticizers, some prominence is given to their effect on the
mechanical properties of the film and its permeability characteristics, especially to water vapour. A
section is provided on the assessment of plasticizer activity on film-coating polymers.
The section on pigments describes how they function as opacifiers and also their ability to modify the
permeability of a film to gases.
In considering the solvents and vehicles used in film-coating techniques a discussion is provided of
the respective merits of aqueous and non-aqueous processing.
The chapter is concluded by some examples of formulae of film-coating systems which illustrate
several of the principles described previously.

2.1 INTRODUCTION

A film coating is a thin polymer-based coat applied to a solid dosage form such as a tablet, granule or
other particle. The thickness of such a coating is usually between 20 and 100 μm. Under close
examination the film structure can be seen to be relatively non-homogeneous and quite distinct in
appearance, for example, from a film resulting from casting a polymer solution on a flat surface. This
non-homogeneous character results from the deliberate addition of insoluble ingredients such as
pigments and by virtue of the fact that the film itself is built up in an intermittent fashion during the
coating process. This is because most coating processes rely on a single tablet or granule passing
through a spray zone, after which the adherent material is dried before the next portion of coating is
received. This activity will of course be repeated many times until the coating is complete.
Film-coating formulations usually contain the following components:
However, while plasticizers have an established place in film-coating formulae they are by no means
universally used. Likewise, in clear coating, pigments and opacifiers are deliberately omitted.
Consideration must also be given to minor components in a film-coating formula such as flavours,
surfactants and waxes and, in rare instances, the film coat itself may contain active material.

2.2 POLYMERS

The vast majority of the polymers used in film coating are either cellulose derivatives, such as the
cellulose ethers, or acrylic polymers and copolymers. Occasionally encountered are high molecular
weight polyethylene glycols, polyvinyl pyrrolidone, polyvinyl alcohol and waxy materials.
The characteristics of the individual polymers and the essential properties of polymers used for film
coating will be covered in subsequent sections.
Frequently, the polymer is dissolved in an appropriate solvent either water or a non-aqueous solvent
for application of the coating to the solid dosage form. However, some of the water-insoluble polymers
are available in a form which renders them usable from aqueous systems. These materials find
considerable application in the area of modified release coatings. Basically there are two classes of such
material depending upon the method of preparation; true latexes and pseudolatexes.

2.2.1 True latexes

These are very fine dispersions of polymer in an aqueous phase and particle size is crucial in the
stability and use of these materials. They are characterized by a particle size range of between 10 and
1000 nm. Their tendency to sediment is counter-
• Polymer.
• Plasticizer.
• Pigment/opacifier.
• Vehicle.
balanced by the Brownian movement of the particles aided by microconvection currents found in the
body of the liquid. The Stokes equation can be used to determine the greatest particle diameter that can
be tolerated in the system without sedimentation. At the other end of the size range the characteristic of
colloidal particles is approached where such dispersions are barely opaque to light and are almost clear.
One of the chief ways of producing latex dispersions is by emulsion polymerization. Characteristically
the process starts with the monomer which after purifica-tion is emulsified as the internal phase with a
suitable surfactant (Lehmann, 1972). Polymerization is activated by addition of an initiator. Commonly
the system is purged with nitrogen to remove atmospheric oxygen which would lead to side reactions.
As with any polymerization process, the initiator controls the rate and extent of the reaction. The
reaction is quenched when the particle size is in the range 50–200 nm. Using this process the following
acrylate polymers are produced: Eudragit L100–55 and NE30D (Lehmann, 1989a).

2.2.2 Psuedolatexes

Commercially there are two main products which fall into this category, both of them utilize
ethylcellulose as the film former but are manufactured in quite a different way and their method of
application also differs significantly. Characteristically pseudolatexes are manufactured starting with the
polymer itself and not the monomer. By a physical process the polymer particle size is reduced thereby
producing a dispersion in water; the characteristics of this dispersion need not differ significantly from a
true latex, including particle size considerations. The pseudolatex is also free of monomer residue and
traces of initiator, etc.
The earliest of the two ethylcellulose products (Aquacoat) is manufactured by dissolving
ethylcellulose in an organic solvent and emulsifying the solution in an aqueous continuous phase. The
organic solvent is eventually removed by vacuum distillation, leaving a fine dispersion of polymer
particles in water. Steuernagel (1989) has defined the composition of Aquacoat to have a solids content
of 30% w/w and a moisture content of 70%w/w, the solids being composed of ethylcellulose 87%, cetyl
alcohol 9% and sodium lauryl sulphate 4%. A food grade antifoam is also present. The cetyl alcohol and
sodium lauryl sulphate act as surfactants/stabi-lizers during the later stages of production.
The newer of the ethylcellulose products is Surelease. This is manufactured using a patented process
based on phase inversion technology (Warner, 1978). The ethylcellulose is heated in the presence of
dibutyl sebacate and oleic acid, and this mixture is then introduced into a quantity of ammoniated water.
The resulting phase inversion produces a fine dispersion of ethylcellulose particles in an aqueous
continuous phase. The dibutyl sebacate (fractionated coconut oil can also be used) is to be found in the
ethylcellulose fraction while the oleic acid and the ammonia together effectively stabilize the dispersed
phase in water. This siting of the dibutyl sebacate and oleic acid is important for the use of this material
as an effective coating agent. Both materials act as plasticizers and with the Surelease system are
physically situated where they are able to function most effectively, that is, in intimate contact with the
polymer. Surelease, unlike Aquacoat, does not require the further addition of plasticizer. Surelease also contains a quantity of fumed silica which acts as an
antitack agent during the coating process. Its total nominal solids content is 25% w/w.
Aqueous dispersions have significant advantages, enabling processing of water-insoluble polymers
from an aqueous media (see Chapter 14).

2.2.3 Mechanism of film formation

Film formation from an aqueous polymeric dispersion is a complex matter and has been examined by
several authors (Bindschaedler et al., 1983; Zhang et al., 1988, 1989). In the wet state the polymer is
present as a number of discrete particles, and these have to come together in close contact, deform,
coalesce and ultimately fuse together to form a discrete film. During processing, the substrate surface
will be wetted with the diluted dispersion. Under the prevailing processing conditions water will be lost
as water vapour and the polymer particles will increase in proximity to each other—a process which is
greatly aided by the capillary action of the film of water surrounding the particles. Complete
coalescence occurs when the adjacent particles are able to mutually diffuse into one another,
Minimum film-forming temperature (MFT)
This is the minimum temperature above which film formation will take place using individual defined
conditions. It is largely dependent on the glass transition temperature (Tg) of the polymer, an attribute
which is capable of several definitions but can be considered as that temperature at which the hard
glassy form of an amorphous or largely amorphous polymer changes to a softer, more rubbery,
consistency. Lehmann (1992) states that the concept of MFT includes the plasticizing effect of water on
the film-forming process. With aqueous dispersions Lehmann recommends to keep the coating
temperature 10–20°C above the MFT to ensure that optimal conditions for film formation are achieved.
Examples of MFTs of Eudragit RL and RS aqueous dispersions are given by Lehmann (1989a).

2.3 POLYMERS FOR CONVENTIONAL FILM COATING

The term conventional film coating has been used here to describe film coatings applied for reasons of
improved product appearance, improved handling, and prevention of dusting, etc. This is to make a
distinction with functional film coats, which will be described in a later section, and where the purpose
of the coating is to confer a modified release aspect on the dosage form. An alternative term for
conventional film coating, therefore, would be non-functional film coating.
2.3.1 Cellulose ethers
The majority of the cellulose derivatives used in film coating are in fact ethers of cellulose. Broadly they
are manufactured by reacting cellulose in alkaline solution with, for example, methyl chloride, to obtain
methylcellulose. Hydroxypropoxyl substitution is obtained by similar reaction with propylene oxide.
The product is thoroughly washed with hot water to remove impurities, dried and finally milled prior to packaging.
The structure of cellulose permits three hydroxyl groups per repeating anhydroglucose unit to be
replaced, in such a fashion. If all three hydroxyl groups are replaced the degree of substitution (DS) is
designated as 3, and so on for lower degrees of substitution. The term molar substitution (MS) covers
the situation where a side chain carries hydroxyl groups capable of substitution and takes into account
the total moles of a group whether on the backbone or side chain. Both DS and MS profoundly affect
the polymer properties with respect to solubility and thermal gel point.
The polymer chain length, together with the size and extent of branching, will of course determine the
viscosity of the polymer in solution. As a generality, film coating demands polymers at the lower end of
the viscosity scale.This polymer provides the mainstay of coating with the cellulose ethers and its usage dates back to
the early days of film coating. It is soluble in both aqueous media and the organic solvent systems
normally used for film coating. HPMC provides aqueously soluble films which can be coloured by the
use of pigments or used in the absence of pigments to form clear films. The polymer affords relatively
easy processing due to its non-tacky nature. A typical low-viscosity polymer can be sprayed from an
aqueous solution containing around 10–15%w/w polymer solids. From the regulatory aspect, in addition
to its use in pharmaceutical products, HPMC has a long history of safe use as a thickener and emulsifier
in the food industry.
USP and JP recognize definite substitution types in separate monographs.
The first two digits of the four-digit designation specify the nominal percentage of methoxyl groups
while the final two specify the nominal percentage of hydroxypropoxyl groups. The EP has no specified ranges for substitution. Significant
differences exist between the USP and EP monographs. These relate to tighter requirements for ash,
chloride for the EP which also possesses tests on solution colour, clarity and pH. Methodology
differences also exist, particularly with regard to solution viscosity. The JP has a very low limit on
chloride content.
Methylcellulose (MC)
Substituent group: —CH3
This polymer is used rarely in film coating possibly because of the lack of commercial availability of
low viscosity material meeting the appropriate compendial requirements. As a distinction from the USP
and the JP the EP has no required limits on the content of methoxyl substitution. However, the USP and
JP have slightly different limits, which are 27.5–31.5% against 26.0–33.0% respectively.
Hydroxyethyl cellulose (HEC)
Substituent group: —CH(OH)—CH3
This water-soluble cellulose ether is generally insoluble in organic solvents. The USNF is the sole
pharmacopoeial specification; there is no requirement on the quantity of hydroxyethyl groups to be
present. The USNF allows the presence of additives to promote dispersion of the powder in water and to
prevent caking on storage.
Hydroxypropyl cellulose (HPC)
Substituent group: —CH2 —CH(OH)—CH3
HPC has the property of being soluble in both aqueous and alcoholic media. Its films unfortunately
tend to be rather tacky, which possess restraints on rapid coating; HPC films also suffer from being
weak. Currently this polymer is very often used in combination with other polymers to provide
additional adhesion to the substrate. The EB/BP has no requirements on hydroxypropoxyl content. The
USNF states this must be less than 80.5% while the JP has two monographs differing in substitution
requirements. The monograph most closely corresponding to the USNF material has a substitution
specification of 53.4–77.5%. The other monograph relates to material of much lower substitution
content and is used for purposes other than film coating, e.g. direct compression.

2.3.2 Acrylic polymers

These comprise a group of synthetic polymers with diverse functionalities.
Methacrylate aminoester copolymer
This polymer is basically insoluble in water but dissolves in acidic media below pH 4. In neutral or
alkaline environments, its films achieve solubility by swelling and increased permeability to aqueous
media. Formulations intended for conventional film coating can be further modified to enhance swelling
and permeability by the incorporation of materials such as water soluble cellulose ethers, and starches in
order to ensure complete disintegration/dissolution of the film.
This material is supplied in both powder form or as a concentrated solution in isopropanol/acetone,
which can be further diluted with solvents such as ethanol, methanol, acetone and methylene chloride.
Talc, magnesium stearate or similar materials are useful additions to the coating formula as they assist in
decreasing the sticky or tacky nature of the polymer. In general, the polymer does not require the
addition of a plasticizer.

2.4 POLYMERS FOR MODIFIED RELEASE APPLICATION

Despite the considerable difference in application between a polymer intended for a simple conventional
(non-functional) coating and one intended to confer a modified release performance on the dosage form,
the categorizing of the polymers themselves into these divisions is not such an exact process. Several
examples exist of polymers fulfilling both needs, hence there is a considerable overlap of use. However,
the divisions used here represent perhaps the majority practice.

2.4.1 Methacrylate ester copolymers

Structurally these polymers bear a resemblance to the methacrylic acid copolymers but are totally
esterified with no free carboxylic acid groups. Thus these materals are neutral in character and are
insoluble over the entire physiological pH range. However they do possess the ability to swell and
become permeable to water and dissolved substances so that they find application in the coating of
modified release dosage forms. The two polymers Eudragit RS and RL, can be mixed and blended to
achieve a desired release profile. The addition of hydrophilic materials such as the soluble cellulose
ethers, polyethylene glycol (PEG), etc., will also enable modifications to be achieved with the final
formulation. The polymer Eudragit RL is strongly permeable and thus only slightly retardant. Its films
are therefore also indicated for use in quickly disintegrating coatings. The polymers themselves have
solubility characteristics similar to the methacrylic acid copolymers.
For aqueous spraying a latex form of each polymer is available. In addition the polymer Eudragit
NE30D has been made for this purpose. This materal is also used as an immediate-release nonfunctional
coating in film coat formulations where relatively large quantities of water-soluble materials
are added to ensure efficient disruption of the coat.

2.4.2 Ethylcellulose (EC)

Substituent group (Fig. 2.2): —CH2—CH3
Ethylcellulose is a cellulose ether produced by the reaction of ethyl chloride with the appropriate
alkaline solution of cellulose. Apart from its extensive use in controlled release coatings, ethylcellulose
has found a use in organic solvent-based coatings in a mixture with other cellulosic polymers, notably
HPMC. The ethylcellulose component optimizes film toughness in that surface marking due to handling
is minimized. Ethylcellulose also conveys additional gloss and shine to the tablet surface.
In many ways ethylcellulose is an ideal polymer for modified release coatings. It is odourless,
tasteless and it exhibits a high degree of stability not only under physiological conditions but also under
normal storage conditions, being stable to light and heat at least up to its softening point of c. 135°C
(Rowe, 1985). Commercially, ethylcellulose is available in a wide range of viscosity and substitution
types giving a good range of possibilities for the formulator. It also possesses good solubility in
common solvents used for film coating but this feature is nowadays of lesser importance with the advent
of water-dispersible presentations of ethylcellulose which have been especially designed for modified
release coatings. The polymer is not usually used on its own but normally in combination with
secondary polymers such as HPMC or polyethylene glycols which convey a more hydrophilic nature to
the film by altering its structure by virtue of pores and channels through which drug solution can more
easily diffuse. Only the USNF contains a monograph, an ethoxy group content of between 44.0 and
51.0% is specified. The USNF also contains a monograph ‘Ethylcellulose Aqueous Dispersion’ which
defines one type of such material which finds a use in aqueous processing. The monograph permits the
presence of cetyl alcohol and sodium lauryl sulphate which are necessary to stabilize the dispersion.

2.5 ENTERIC POLYMERS

As will be seen later, enteric polymers are designed to resist the acidic nature of the stomach contents,
yet dissolve readily in the duodenum.

2.5.1 Cellulose acetate phthalate (CAP)

Substituent groups: —CO—CH3, —CO—C6H4—COOH
This is the oldest and most widely used synthetic enteric coating polymer patented as an enteric agent
by Eastman Kodak in 1940. It is manufactured by reacting a partial acetate ester of cellulose with
phthalic anhydride. In the resulting polymer, of the free hydroxyl groups contributed by each glucose
unit of the cellulose chain, approximately half are acylated and one-quarter esterified with one of the
two carboxylic acid groups of the phthalate moiety. The second carboxylic acid group being free to form
salts and thus serves as the basis of its enteric character.
CAP is a white free-flowing powder usually with a slightly odour of acetic acid. Among the
pharmacopoeias it is found in the EP, JP and USNF. The USNF and JP impose specifications for the
percentage content of the substituent groups. The JP has requirements for the content of acetyl and
phthalyl to be respectively 17–22 and 30–40% while the USNF requires 21.5–26 and 30–36%
respectively. The JP is alone in not specifying any viscosity control on a standard solution. All three
pharmacopoeias require a maximum limit on the quantity of free acid (JP specifies phthalic acid) and
loss on drying (EP specifies water content). The last two parameters are important as CAP is somewhat
prone to hydrolysis.
Of the generally accepted solvents used for tablet coating, CAP is insoluble in water, alcohols and
chlorinated hydrocarbons. In the following solvents or solvent mixtures.
A pseudolatex version of CAP is available (Aquateric) as a dry powder for reconstitution in water and
offers the convenience of aqueous-based processing.
Owing to their chemical constitution, most of the phthalate-based enteric coating agents are to a
greater or lesser degree unstable. This important aspect is dealt with in more detail in Chapter 14, along
with the implications this has on the use of the materal in practice.

2.5.2 Polyvinyl acetate phthalate (PVAP)

PVAP was first patented by the Charles E. Frost Company of Canada and was subsequently investigated
by Millar (1957) who studied the effect that the phthalyl content of the polymer had upon the pH of
disintegration of tablets coated with the material. He found the optimal phthalyl content to be between
60 and 70%. However, given the characteristics of the polymer commercially available nowadays, this
range has been revised and now forms part of the USNF monograph. It is manufactured by reacting
polyvinyl alcohol with acetic acid and phthalic anhydride.
The USNF contains a monograph specifying a total phthalate content of between 55 and 62%. The
polymer characteristics are further controlled by imposition of a viscosity specification. The extent of
hydrolysis, while much less likely than CAP for instance, is controlled with a limit on free phthalic acid
and other free acids. As the final separation process is from water, a limit of 5% of water is specified.
Polyvinyl acetate phthalate possesses the following solubility characteristics, with the extent of
solubility given in parentheses:
methanol (50%)
methanol/methylene chloride (30%)
ethanol 95% (25%)
ethanol/water 85:15 (30%)
An aqueous dispersible form (Sureteric) is available for water-based spraying.

2.5.3 Shellac

This is a purified resinous secretion of the insect Laccifer lacca, indigenous to India and other parts of
the Far East. Shellacs can be modified to suit specialized needs. For instance, bleached shellac is
produced by dissolving crude shellac in warm soda solution followed by bleaching with hypochlorite.
Various grades of dewaxed material can be produced by removing some or all of the approximately 5%
of wax in the final shellac.
Shellac is insoluble in water but shows solubility in aqueous alkalis; it is moder-ately soluble in warm
ethanol.
Over the years, shellac has been used for a variety of applications, which have included.
For all these applications, shellac suffers from the general drawback that it is a material of natural
origin and consequently suffers from occasional supply problems and quality variation. As will be
described later, there are also stability problems associated with increased disintegration and dissolution
times on storage.

2.5.4 Methacrylic acid copolymers

Because these polymers possess free carboxylic acid groups they find use as enteric-coating materials,
forming salts with alkalis and having an appreciable solubility at pH in excess of 5.5
Of the two organic solvent soluble polymers, Eudragit S100 has a lower degree of substitution with
carboxyl groups and consequently dissolves at higher pH than Eudragit L100. Used in combination,
these materials are capable of providing films with a useful range of pH over which solubility will
occur.
All the polymers shown in Table 2.5 are recommended to be used with plasticizers. Pigments and
opacifiers are useful additions as they counteract the sticky nature of the polymers. A feature of these
polymers is their ability to bind large quantities of pigments—approximately two or three times the
quantity of polymer used. Polyethylene glycols are frequently added as they provide a measure of gloss
to the final product. They also assist in stabilizing the water-dispersible form, Eudragit L30D. Pigment
and other additions to the water-dispersible forms Eudragit, L30D and L100–55, should be performed
according to the manufacturer’s recommendations to prevent coagulation of the coating dispersion.
• A seal coat for tablet cores prior to sugar coating.
• An enteric-coating material. This application is really of historic interest only as shellac has a
relatively high apparent pKa of between 6.9 and 7.5 and leads to poor solubility of the film in the
duodenum (Chambliss, 1983).
• A modified release coating.
These polymers comply with the USNF requirements for methacrylic acid copolymer as outlined in
Table 2.5. Both Eudragit L100 and S100 are available in powder form and for convenience purposes
they are also available as concentrates in organic solvent solution, which are capable of further dilution
in the common processing solvents used in organic solvent-based film coating. As previously indicated,
two further commercial forms are available, first, a 30% aqueous dispersion, Eudragit L30D, and,
secondly, a water-dispersible powder, Eudragit L100–55.

2.5.5 Cellulose acetate trimellitate (CAT)

Substituent groups (Fig. 2.2): —CO—CH3, CO—C6H3—(COOH)2
Chemically this polymer bears a strong resemblance to cellulose acetate phthalate but possesses an
additional carboxylic acid group on the aromatic ring. Manufacturer’s quoted typical values for
timellityl and acetyl percentages are 29 and 22% respectively. The useful property of this polymer is its
ability to start to dissolve at the relatively low pH of 5.5 (Anon., 1988) which would help ensure
efficient dissolution of the coated dosage form in the upper small intestine.
As yet, CAT does not appear in any pharmacopoeia but is the subject of a US FDA Drug Master File.
The solubility of CAT in organic solvents is similar to that for CAP. For aqueous processing, the
manufacturers recommend the use of ammoniacal solutions of CAT in water, and fully enteric results
are claimed. The recommended plasticizers for aqueous use are triacetin, acetylated monoglyceride or
diethyl phthalate.

2.5.6 Hydroxypropyl methylcellulose phthalate (HPMCP)

Substituent groups: —CH3, —CH2CH(OH)CH3, —CO—C6H4—COOH
HPMCP is prepared by treating hydroxypropyl methylcellulose with phthalic acid. The degree of
substitution of the three possible substituents determines the polymer characteristics, in particular the
pH of dissolution.
HPMCP may be plasticized with diethylphthalate, acetylated monoglyceride or triacetin.
Mechanically it is a more flexible polymer and on a weight basis will not require as much plasticizer as
CAP or CAT.
HPMCP is a white powder or granular material; monographs can be found in both the USNF and JP.
Both pharmacopoeias describe two substitution types, namely HPMCP 200731 and 220824. The sixdigit
nomenclature refers to the percentages of the respective Substituent methoxyl, hydroxypropoxyl
and carboxy-benzoyl groups. For example, HPMCP 200731 has a nominal methoxyl content of 20%
and so on for the other two substituents. Substitution requirements are the same in both pharmacopoeias.
Commercial designations such as ‘50’ or ‘55’ refer to the pH (×10) of the aqueous buffer solubility.
Fine particle size grades designated with a suffix ‘F’ are intended for suspension in aqueous systems,
with suitable plasticizers prior to spray application.
HPMCP is insoluble in water but soluble in aqueous alkalis and acetone/water 95:5 mixtures.

2.6 POLYMER CHARACTERISTICS

2.6.1 Solubility

Inspection of the solubility characteristics of the film-coating polymers show that the following have a
good solubility in water: HPMC, HPC, MC, PVP, PEG plus gastrointestinal fluids and the common
organic solvents used in coating.
Acrylic polymers used for conventional film coating include methacrylate amino ester copolymers.
These bcome water soluble by swelling, increasing permeability in aqueous media. The polymer in its
unmodified form is however soluble only in organic solvents.
Where it is proposed to use an aqueous solvent for film coating it is necessary to consider, first, the
need to minimize contact between the tablet core and water and, secondly, the need to achieve a
reasonable process time. Both can be achieved by using the highest possible polymer concentration (i.e.
the lowest possible water content). The limiting factor here is one of coating suspension viscosity.

2.6.2 Viscosity

HPMC coating polymers, for example, are available in a number of viscosity designations defined as the
nominal viscosity of a 2%w/w aqueous solution at 20°C. Thus a 5mPa s grade will have a nominal
viscosity of 5 mPa s in 2% aqueous solution in water at 20°C and similarly with 6 mPa s, 15 mPa s and
50 mPa s grades. Commercial nomenclature for these grades may still describe them as ‘5 cP’ etc.
Commercial designations such as E5 (Methocel) or 606 (Pharmacoat) also correspond with the viscosity
designation, such that for example Methocel E5 has a nominal viscosity of 5mPa s under the previously
described standard conditions. While Pharmacoat 606 would have a nominal viscosity of 6 mPa s under
the same conditions.
Considering the final polymer solution to be sprayed, a normal HPMC-based system would have a
viscosity of approximately 500 mPa s. Inspection of Fig. 2.3 shows that if, for instance, a 5 mPa s grade
is used (E5) a solids concentration of about 15%w/w can be achieved. This has the advantage over, for
example, a coating solution prepared from a 50 mPa s grade (E50) where only a 5%w/w solids
concentration could be achieved. The lower viscosity grade polymer permits a higher solids
concentration to be used, with consequent reduction in solvent content of the solution. The practical
advantage to be gained is that the lower the solvent content of the solution, the shorter will be the
processing time as less solvent has to be removed during the coating procedure. This beneficial interaction between polymer viscosity and possible coating
solids is self-limiting in that very low viscosity polymers will suffer from poor film strength due to low
molecular weight composition. Delporte (1980) has examined polymer solution viscosities in the 250–
300 mPa s range and has concluded that 5 mPa s HPMC is preferable to the use of 15 mPa s material.
Furthermore, Delporte advocated the use of elevated temperature coating media in order to additionally
increase solids loadings via a decrease in viscosity.

2.6.2 Permeability

One of the reasons for coating tablets is to provide a protection from the elements of the atmosphere
such that a shelf-life advantage for the product may be gained.
With the continuing change from sugar- to film-based coating has come associated problems of
stability due to sugar-coating techniques providing a better moisture barrier than that offered by simple
non-functional cellulosics or acrylics. Usually the moisture permeability of a simple film may be
decreased by the incorporation of water-insoluble polymers, however disintegration and dissolution
characteristics of the dosage form must be carefully checked.
Permeability effects can be assessed practically by a technique of sealing a sample of cast film over a
small container of desiccant or saturated salt solution, the permeability to water vapour being followed
by successive weighings to determine respectively weight gain or weight loss (Hawes, 1978). In
addition to being tedious to perform, the results are only comparable when performed under identical
conditions. Using similar techniques Higuchi & Aguiar (1959) demonstrated that water vapour
permeability of a polymer is dependent on the relative polarity of the polymer. Both Hawes (1978) and
Delporte (1980) have seen little difference in water vapour permeability between two commercial
grades of HPMC (E5 and E15) which differ only in molecular weight. Okhamafe & York (1983) have
used an alternative method of assessing water vapour permeability, and that is a sorption-desorption
technique to evaluate the performance of two film-forming polymers, HPMC (606) and polyvinyl
alcohol (PVA). Addition of PVA to the HPMC was seen to enhance very effectively the moisture barrier
effect of the HPMC. The authors ascribe this behaviour to the possible potentiation of the crystallinity of
the HPMC by the PVA.
Sometimes permeability of other atmospheric gases is of concern, particularly that of oxygen. This
area has been studied by Prater et al. (1982) who examined the permeability of oxygen through films of
HPMC. These workers used a specially constructed cell which held a 21 mm diameter sample of the
film. The passage of gas into the acceptor portion of the cell was monitored by using a mass
spectrometer detection system. Earlier, Munden et al. (1964) had also determined oxygen permeability
through free films of HPMC. They concluded that there was an inverse relationship between oxygen
permeation and water vapour transmission. These results were obtained using a technique of sealing the
films across a container of alkaline pyrogallol and measuring the consequent solution darkening. As
Prater et al. (1982) point out, this method is not only tedious but water vapour from the pyrogallol is
capable of plasticizing the film and modifying the result.

2.6.4 Mechanical properties

Some of the film mechanical properties of concern are:
• tensile strength
• modulus of elasticity
To perform any function a film coat must be mechanically adequate so that in use it does not crack,
split or generally fail. Also, during the rigours of the coating process itself the film is often relied upon
for the provision of some mechanical strength to protect the tablet core from undue attrition.
These attributes may be conveniently measured by tensile tests on isolated films although other
techniques such as indentation tests have a part to play. Much discussion has also taken place in the
literature on the merits and validity of examining isolated films as opposed to examination of a film
produced under the actual conditions of coating. Both arguments have been reviewed by Aulton (1982).
Suffice it to say that much useful data can be obtained relatively easily from isolated films which, in
practice, has demonstrated the validity of such techniques.

• work of failure
• strain.
• Tensile strength: The most important parameter here is the ultimate tensile strength, which is the
maximum stress applied at the point at which the film breaks.
• Tensile strain at break: A measure of how far the sample elongates prior to break.
• Modulus (elastic modulus): This is applied stress divided by the corresponding strain in the
region of linear elastic deformation. It can be regarded as an index of stiffness and rigidity of a
film.
• Work of failure: This is numerically equivalent to the area under the curve and equates to the
work done in breaking the film. It is an index of the toughness of a film and is a better measure of
the film’s ability to withstand a mechanical challenge than is a simple consideration of tensile
strength All these properties of a polymer film are related to its molecular weight which, in turn,
affects the viscosity of the polymer in solution. In general, apart from the acrylics, the different types of
individual polymers are available in various commercial viscosity designations. These designations rely
on the description of a standard solution in a specified solvent, as previously indicated.2.6.5 Tackiness
In a film-coating sense, tack is a property of a polymer solution related to the forces necessary to
separate two parallel surfaces joined by a thin film of the solution. It is a property responsible for
processing difficulties and is a limitation on the use of some polymers, e.g. hydroxypropyl cellulose
Table 2.6 Mechanical properties of polymers for film coating of drugs
σR (N/mm2) R (%)
Cellulose derivative
HP-50 39 12
HP-55 33 6
CMEC (Duodcell)d 11 5
CAP+25% DEP 16 14
Pharmacoat 606 44 13
Pharmacoat 603e 22 3
Methocel E5e 24 4
Poly(meth)acrylate
MA-MMA 1:2 = Eudragit S100 52 3
MA-MMA 1:1=Eudragit L100 24 1
MA-EA 1:1=Eudragit L100–55a 10 14
Eudragit RS100b 5 40
Eudragit RL100b 5 22
Eudragit E100b 2 200
EA-MMA 1:1=Eudragit E30D 8 600
Eudragit E30D/L30D 1:1 17 75
Eudragit E30D/L100 7:3c 7 410
Eudragit E30D/S100 7:3c 2 620
Eudragit E30D/E100-citrat 4:1 4 400
Eudragit E30D/E100-phosphat 4:1 5 360
Other polymers
Polyvinylacetate phthalatef 31 5
Note: σR=tensile strength at break (after DIN 53455; R=elongation at break).
a 10% PEG.
b 10% Triacetin
c 10% Tween 80
d 30% Glycerylmonocaprylate.
e 20% PEG.
f 10% Diethylphthalate.
(Porter & Bruno, 1990) and certain polymers intended for enteric use, e.g. Eudragit L30D and PVAP.
Kovacs & Merenyi (1990) examined several polymers using a technique combining measure

2.7 PLASTICIZERS

Plasticizers are simply relatively low molecular weight materials which have the capacity to alter the
physical properties of a polymer to render it more useful in performing its function as a film-coating
material. Generally the effect will be to make it softer and more pliable. There are often chemical
similarities between a polymer and its plasticizer—for instance, glycerol and propylene glycol, which
are plasticizers for several cellulosic systems, possess —OH groups, a feature in common with the
polymer.
It is generally considered that the mechanism of action for a plasticizer is for the plasticizer molecules
to interpose themselves between the individual polymer strands thus breaking down to a large extent
polymer-polymer interactions. This action is facilitated as the polymer-plasticizer interaction is
considered to be stronger than the polymer-polymer interaction. Hence, the polymer strands now have a
greater opportunity to move past each other. Using this model it can be visualized how a plasticizer is
able to transform a polymer into a more pliable material.
Most of the polymers used in film coating are either amorphous or have very little crystallinity.
Strongly crystalline polymers are difficult to plasticize in this fashion as disruption of their
intermolecular structure is not an easy matter. Experimentally, the effect of a plasticizer on a polymeric
system can be demonstrated in many ways; for instance, isolated film work using tensile or indentation
methods will reveal significant changes in mechanical properties between the plasticized and
unplasticized states.
One fundamental property of a polymer which can be determined by several techniques is the glass
transition temperature (Tg). This is the temperature at which a polymer changes from a hard glassy
material to a softer rubbery material. The action of a plasticizer is to lower the glass transition
temperature. The transition can be followed by examining the temperature dependence of such
properties as modulus of elasticity, film hardness, specific heat, etc. These properties will be expanded
on later. Sakellariou et al. (1986a) have utilized a dynamic mechanical method, namely torsion braid
analysis, to characterize the effect of PEGs on HPMC and ethylcellulose.

2.7.1 Classification

The commonly used plasticizers can be categorized into three groups:
1. Polyols
(a) glycerol (glycerin);
(b) propylene glycol;
(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.

2.7.2 Compatibility and permanence

It follows from what has been described above regarding plasticizer-polymer interactions that one
attribute of an efficient platicizer could be that it acts as a good solvent for the polymer in question.
Indeed, Entwistle & Rowe (1979) have used this as a measure of plasticizer efficiency. They found a
correlation between the intrinsic viscosity of the polymer/plasticizer solutions and the mechanical
attributes of polymer films plasticized with the specified plasticizers—the mechanical properties of
tensile strength, elongation at rupture and work of failure being at a minimum when the intrinsic
viscosity of the polymer/plasticizer solution was at a maximum.
With the predominance today of aqueous-based film coating there is a concentration on those
plastizers with an appreciable water miscibility. This includes the polyols and, to a lesser extent,
triacetin and triethylcitrate. Glycerol has the added advantage that its regulatory acceptance for food
supplement products (e.g. vitamin and mineral tablets) is greater than for other plasticizers in those parts
of the world where this type of product is covered by food legislation. Permanence of the more volatile
plasticizers, e.g. diethylphthalate (DEP), can be a problem with organic solvent-based processing and
likewise in the aqueous field utilizing propylene glycol as the plasticizer. Permanence is an attribute to
be taken into consideration as loss of plasticizer, for instance during storage of the coated tablets, could
have serious consequences on the integrity of the dosage form. One such consequence could lead to the
cracking of the coating under inappropriate storage. These considerations are of much greater
significance in the realm of functional coatings. 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. An example here would be the change from a low molecular PEG
to a high molecular PEG such as the 6000 grade. This move has unfortunately brought with it a change
to a less effective plasticizer. Regarding losses during processing, Skultety & Sims (1987) have shown
that, in a statistically based study to determine the factors involved in the loss of propylene glycol
during the coating process, values of 81–96% of theoretical were shown. The only independent variable
in the study having an effect was the initial concentration of propylene glycol. On the other hand, no
loss was seen when either glycerol or PEG was used as the plasticizer.
The possibility of plasticizer migration should also be considered. Conceivably this can occur in two
ways:
A related phenomena is the migration of materials from the tablet core into the film coating which
may themselves have a plasticizer-like action on the polymer used. Abdul-Razzak (1983) demonstrated
the migration of several salicylic acid deriva-
3. Oils/glycerides
(a) castor oil;
(b) acetylated monoglycerides;
(c) fractionated coconut oil.
• migration into the tablet core.
• migration into packaging materials.
A related phenomena is the migration of materials from the tablet core into the film coating which
may themselves have a plasticizer-like action on the polymer used. Abdul-Razzak (1983) demonstrated
the migration of several salicylic acid deriva-tives into an ethylcellulose film coating where the derivatives concerned possessed plasticizer activity
for ethylcellulose. Later, Okhamafe & York (1989) examined the effect of ephedrine hydrochloride on
both HPMC and PVA. This drug was shown to display strong plasticizer characteristics for both
polymers, namely a decrease in softening temperature Tg, crystallinity and melting point. Again, the
consequences of this are rather more serious with functional than non-functional coatings, as the
pharmaceutical performance of the film could be compromised.

2.7.3 Effect of plasticizers on the mechanical properties of the film

This can be quite profound and capable of making significant alterations to its properties, either
advantageously or adversely.
changes in relation to tensile properties can be summarized as
follows:
Returning to the earlier proposed mechanism of plasticizer action, it can be seen that as a plasticizer
interacts with a polymer the structure of that polymer will be modified so as to permit increased
segmental movement. The tertiary structure of the polymer will therefore be altered in such a way as to
give a more porous, flexible and less cohesive structure. When a plasticized polymer is subjected to a
tensile force it can be seen that this structure would be less resilient and would deform at a lower force
than without the plasticizer.
Aulton et al. (1981) have utilized an ‘Instron’ materals tester to evaluate the effect of a series of
plasticisers on the mechanical properties of cast films of HPMC (Methocel E5). Of particular interest
was the finding that low molecular weight PEG was a more efficient plasticizer for this polymer than
corresponding high molecular weight grades (Fig. 2.7). The authors also examined films using the
technique of indentation. This showed that the introduction of plasticizer to the polymer film promoted
increasing viscoelastic behaviour in the polymer. Indentation studies at low and high humidity also
provided experimental evidence for the plasticizing effect of water on HPMC films. Porter (1980) and
Delporte (1981) are in general agreement with the findings of Aulton et al. (1981) and, interestingly,
Porter used a technique whereby the film for investigation was obtained by spraying and not by casting.
Okhamafe & York (1983) have also studied the effects of PEG and HPMC films. Again they are in
agreement with the findings of Aulton et al. (1981) in that PEG 400 was preferable to PEG 1000. This
view was also held by Entwistle & Rowe (1979) using their technique involving polymer/plasticizer
solution viscosity determination. Okhamafe & York (1983) also showed that polyvinyl alcohol (PVA)
had a quantitatively different effect on HPMC to that displayed by the PEGs. PVA decreases to a lesser
degree, the decrease seen in tensile strength and the increase seen in elongation compared with the
PEGs. The authors postulate an increasing crystallinity as a result of PVA addition to the film. It is also
noted from the results
• Increase in strain or film elongation
• Decrease in elastic modulus
• Decrease in tensile strength.
Returning to the earlier proposed mechanism of plasticizer action, it can be seen that as a plasticizer
interacts with a polymer the structure of that polymer will be modified so as to permit increased
segmental movement. The tertiary structure of the polymer will therefore be altered in such a way as to
give a more porous, flexible and less cohesive structure. When a plasticized polymer is subjected to a
tensile force it can be seen that this structure would be less resilient and would deform at a lower force
than without the plasticizer.
Aulton et al. (1981) have utilized an ‘Instron’ materals tester to evaluate the effect of a series of
plasticisers on the mechanical properties of cast films of HPMC (Methocel E5). Of particular interest
was the finding that low molecular weight PEG was a more efficient plasticizer for this polymer than
corresponding high molecular weight grades (Fig. 2.7). The authors also examined films using the
technique of indentation. This showed that the introduction of plasticizer to the polymer film promoted
increasing viscoelastic behaviour in the polymer. Indentation studies at low and high humidity also
provided experimental evidence for the plasticizing effect of water on HPMC films. Porter (1980) and
Delporte (1981) are in general agreement with the findings of Aulton et al. (1981) and, interestingly,
Porter used a technique whereby the film for investigation was obtained by spraying and not by casting.
Okhamafe & York (1983) have also studied the effects of PEG and HPMC films. Again they are in
agreement with the findings of Aulton et al. (1981) in that PEG 400 was preferable to PEG 1000. This
view was also held by Entwistle & Rowe (1979) using their technique involving polymer/plasticizer
solution viscosity determination. Okhamafe & York (1983) also showed that polyvinyl alcohol (PVA)
had a quantitatively different effect on HPMC to that displayed by the PEGs. PVA decreases to a lesser
degree, the decrease seen in tensile strength and the increase seen in elongation compared with the
PEGs. The authors postulate an increasing crystallinity as a result of PVA addition to the film. It is also
noted from the results that the elongation effect obtained by the addition of PEG and PVA to the films exhibits anisotropy. The
authors speculate as to whether this is a real effect or whether it is due to the experimental protocol.
Dechesne and Jaminet (1985) have studied the mechanical properties of cellulose acetate phthalate
when plasticized by triacetin, DEP and Citroflex A2 in a statistically designed study. One interesting
feature was that triacetin was shown to be a very potent plasticizer for CAP. A practical point of
significance is the ability of plasticizers to lower the residual internal stress within a film coating. This is
accomplished by the effect of the plasticizer on the modulus of elasticity of the film (Rowe, 1981). This
aspect will be dealt with in greater detail in the problem-solving section, Chapter 13.
Another important point is that film coatings which confer a modified release effect on the dosage
form need to be mechanically tough in order that the coating is not inadvertently damaged during
normal handling. Dechesne et al. (1982) emphasized the activity of plasticizers in their investigation of
the effect that different plasticizers have on the diametral crushing strength of, in this case, sodium
fluoride tablets. At an application level of 10 mg of Eudragit L30D/cm2 for example, considerable
differences were evident in the behaviour of six different plasticizers. Crushing strengths of
approximately 4.75 kg were recorded employing dibutyl phthalate compared with a value of almost 10
kg when propylene glycol was used.

2.7.4 Effect of plasticizers on permeability of film coatings

Occasionally it is required to optimize the permeability characteristics of a film in order to use the film
coat to retard the entry of water vapour or other gases into the dosage form. This is another area in
which plasticizers have a part to play. The transport of a permeant across a barrier is defined by Crank’s
relationship (see Okhamafe & York, 1983)
P=D·S
(2.2)
where P, D and S are the permeability, diffusion and solubility coefficients respectively of the film
coating. It can be envisaged that the passage of a permeant across the film is governed by two steps:
1. Dissolution of the permeant in the film material.
2. Diffusion of the permeant across the film.
In turn, this later process can take place by the permeant diffusing through the polymer matrix itself
and/or diffusion through voids containing either true liquids or vapours. It follows, therefore, that as a
plasticizer has the capacity to alter the structure of a polymer, these materials will have the ability to
alter the permeability characteristics of a film coating. The above authors have determined the diffusion
coefficients for water through HPMC films plasticized with PEG 400 and 1000, and in both cases an
increase was observed. Previously Porter (1980) and Delporte (1981) had been unable to demonstrate
any significant effect with PEG.

2.7.5 Measurement and characterization of plasticizer activity

Thermal method
This method has proved ideally suited to investigate plasticizer activity, in particular determination of
the glass transition temperature, Tg. This attribute of a polymer is readily detected as an endotherm prior
to the endotherm resulting from melting or decomposition. Other endotherms may be seen usually at
lower temperatures, resulting from loss of solvent from the polymer.
Using these techniques several authors have demonstrated correlations between plasticizer concentration
and degree of lowering of Tg (Porter & Ridgway, 1983; Dechesne et al., 1984).
Thermomechanical analysis
Like DSC this method has the useful feature that actual plasticized films can be used for the
determination. Using the technique (Fig. 2.8) a film sample is placed in a holder, and at the
commencement of the experiment a weighted stylus is brought into contact with the specimen.
Indentation of the stylus into the specimen as the temperature is gradually raised is followed by an
LVDT. The temperature rise of the specimen is accompanied by changes in the polymer structure,
which are reflected by movement of the LVDT trace. Hence changes due to softening, melting
decomposition and glass transitions can be readily followed (Fig. 2.9) (see also Masilungan & Lordi
1984; Majeed, 1984).
Mechanical methods
Mention has already been made of tensile and indentation methods. Depending on the area of interest,
such parameters as decrease in tensile strength, increase in strain (elongation) or changes in the modulus
of elasticity with changes in plasticizer concentration can be followed. Sinko & Amidon (1989) have
used low strain elongational creep compliance to analyse the intrinsic mechanical response of films of
Eudragit S100 with different plasticizers. They studied plasticizer-induced changes on the rate of
mechanical response as solvent leaves the film and the polymer passes through a rubber to glass
transition. Using a free volume analysis, a plasticizing effectiveness term was calculated for the
plasticizers used in this study. This showed, for instance, that for Eudragit S100 films, dibutyl phthalate
is a more efficient plasticizer than PEG 200.
Solubility methods
These methods usually rely on a consideration of the solubility parameter.
In order for a polymer to dissolve in a solvent (plasticizer) the Gibbs free energy of mixing, ΔG, must
be negative:
ΔG=ΔH−T·ΔS
(2.3)
where ΔH is the heat of mixing, T the absolute temperature and ΔS the entropy of mixing.
Okhamafe & York (1987) have demonstrated how ΔH may be obtained from the following
relationship due to Hildebrand and Scott (1950).

2.8 COLOURANTS/OPACIFIERS

• Identification of the product by the manufacturer and therefore act as an aid (not a replacement)
for existing GMP procedures. Colourants also aid in the identification of individual products by
patients, particularly those taking multiple medication.
• They reinforce brand imaging by a manufacturer and thereby decrease the risk of counterfeiting.
• Colourants for film-coated tablets have to a greater or lesser extent opacifying properties which
are useful when it is desired to optimize the ability of the coating to protect the active ingredient
against the action of light.

2.8.1 Classification

Organic dyes and their lakes
This group would include such materials as Sunset Yellow, Patent Blue V, Quinoline Yellow, etc. As
water solubles their use is extremely restricted regarding the colouring of any form of coated tablet.
However, their water-insoluble complexes with hydrated alumina, known as lakes, are in widespread
use as colours for coated tablets. The reason for this will be considered in the appropriate section below.
In the laking process a substratum of hydrated alumina is produced by reacting aluminium chloride with
sodium carbonate. The appropriate dye in aqueous solution is then adsorbed onto the prepared alumina
hydrate. Finally additional aluminium chloride is added to ensure complete formation of the aluminium
salt of the dye. Filtration and washing of the product complete the process.
Inorganic colours
Stability towards light is an important characteristic displayed by these materials, some of which have a
useful opacifying capacity, e.g. titanium dioxide. Another great advantage of inorganic colours is their
wide regulatory acceptance, making them most useful for multinational companies wishing to
standardize international formulae. One drawback to their use is that the range of colours that can be
achieved is rather limited.
Natural colours
This is a chemically and physically diverse group of materials. The description ‘natural’ is of necessity
loose, as some of these colours are the products of chemical synthesis rather than extraction from a
natural source, e.g. (β-carotene of commerce is regularly synthetic in origin. The term frequently applies
to such materials is ‘nature identical’, which in many ways is more descriptive. Some would even make
the case that any product which is not a constituent of the normal diet should not be called ‘natural’.
This viewpoint would remove colours such as cochineal and annatto from consideration. As a
generalization, natural colours are not as stable to light as the other groups of colours; their tinctorial
powers are not high and they tend to be more expensive than other forms of colour. They do, however,
possess a regulatory advantage in that they have a wide acceptability. Even with these advantages their
penetration into the pharmaceutical area has not been great.

This group of materials are commonly used as ingredients in film-coating formulae. They obviously
contribute to the aesthetic appeal of the product, but they also enhance the product in other ways:
Examples of colours:
Organic dyes and their lakes
Inorganic colours
Natural colours

2.8.2 Regulatory aspects and specifications

Pharmaceutical colours are unusual in that, in most parts of the world, they are subject to requirements
over and above normal pharmacopoeial specifications. For example, within the EU they must meet
certain purity requirements laid down by current European Union Directives. Likewise, in the United
States, the Code of Federal Regulations imposes its own set of purity criteria. Countries can and
frequently do differ in the colours that are permitted in pharmaceutical preparations. Specialist
publications exist which should be consulted in case of doubt (e.g. Anon., 1993).

2.8.3 Advantages of pigments over dyes

Previously it had been indicated that water-soluble colours were technically inferior to water-insoluble
(pigments) colours. The reasons for this are given below.
Migration
Drying is an integral part of the coating process and, as a consequence, water will leave the film coat
continuously as the coat is formed. If the colour is in the form of insoluble particles, then no migration
takes place. However, a water-soluble colour tends to follow the escaping water molecules to the tablet
surface and produce a mottled finish to the coating.
Opacity
Pigments are much more opaque than dyes, hence they offer a much greater measure of protection
against light than dye-coloured film coats.
Colour stability
Edible colours for medicinal products have an established use by virtue of their low order of toxicity.
Some of their technical attributes, for example colour stability, can represent somewhat of a
compromise. In general the inorganic pigments, e.g. iron
• Sunset Yellow
• Tartrazine
• Erythrosine.
• Titanium dioxide
• Iron oxide yellow, red and black
• Talc.
• Riboflavine
• Carmine
• Anthocyanins.
oxides, have an excellent stability while the synthetic organic dyes are much less satisfactory in this
respect. The lake forms of many of the synthetic organic dyes, however, provide a degree of
improvement in this respect.
Permeability
Pigments decrease the permeability of films to water vapour and oxygen thereby offering the
possibilities of increased shelf-life.
Coating solids
Pigments contribute to the total solids of a coating suspension without significantly contributing to
the viscosity of the system. Thus faster processing times by virtue of more rapid drying is possible. This
is particularly significant with aqueous-based processes.
Anti-tack activity
Tack is a concept that is widely used to describe the forces involved in the separation of two parallel
surfaces separated by a thin film of liquid. Such considerations are important during the coating process
as excess tack can cause troublesome adhesion of tablets to each other or to the coating vessel. Since the
early days of film coating it has been appreciated that solid inclusions, including pigments, in the
formula have a part to play in combating the effects of tack. Chopra & Tawashi (1985) have quantified
the action of titanium dioxide, talc and indigo carmine lake on the tackiness of coating polymer
solutions. They have shown that, at high polymer concentrations, increasing the pigment concentration
and decreasing the pigment particle size, reduced the effect of tack, whereas at low polymer
concentration only talc was effective in reducing tack. Alternative methods of tack evaluation have been
utilized by other workers such as Massoud & Bauer (1989) and Wan & Lai (1992).

2.8.4 Effects of pigments on film-coating systems

Because of their very diverse nature it can be expected that the effects of pigments on film-coating
systems can be rather complex.
Mechanical effects
In general, the presence of pigments will reduce the tensile strength of a film, increase the elastic
modulus and decrease the extension of the film under a tensile load. All of these are, of course, negative
effects. However, as pigments consist of discrete individual particles the need for efficient pigment
dispersion should be emphasized. Another generalization is that the lower the particle size of the
pigment concerned, the smaller will be the deleterious effect on film properties. These effects are of
some importance in the consideration of stress-related film-coating defects. Lehmann & Dreher (1981)
describe the property displayed by several of the acrylic film-coating polymers, that of being able to
bind substantially higher quantities of pigment than is possible for example with the cellulosics. The
authors point to the advantages of mechanical stability and resistance to attrition achieved.
Aulton et al. (1984) have examined the effect of a wide range of pigments on the mechanical
properties of cast films of HPMC (Methocel E5). In addition to confirming the general effects above,
they emphasized the need to consider the whole stress-strain diagram and not to merely one feature in
isolation. For instance, a pigmented film may well show very little decrease in tensile strength compared
with the unpigmented film; however, a consideration of the area under the curve could show significant
differences . The term ‘work of rupture’ was coined by the authors for this particular
parameter. In comparing the effects of different pigments the authors concluded that there were
pigment-specific effects and that the pigment was not merely occupying space in an inert manner or
behaving as an inert diluent. The pigment effect has also been discussed by Rowe (1982) in a study on
the effect of pigments on edge splitting of tablet film coats. Talc was seen to be an exception to the
general behaviour of pigments. The reason postulated was that as talc exists as flakes it orientates itself
parallel to the surface of the substrate in a restraint on volume shrinkage of the film parallel to the plane
of coating .
In another study, Okhamafe & York (1985a) have looked at the mechanical properties stated above
for free films in combination with PVA or PEG 1000 and loaded with talc or titanium dioxide. Broadly,
the results were in agreement with the findings of Aulton et al. (1984). The results were presented not
only in mechanical terms but polymer-pigment interactions were also taken into account in either rein-forcing the mechanical effect or working against it. For example, in the case of high pigment-polymer
interaction, the loss of film elongation was greatly potentiated.
The same authors, in further work (1985b), have examined the effect of pigmented and unpigmented
films on the adhesion of those films to the surfaces of aspirin tablets. They found that pigments
incorporated in an applied film can exert two opposing effects on adhesion: one decreases adhesion by increasing internal stress and the other
increases adhesion by strengthening the film-tablet surface interation. From the results obtained, the
adhesion of HPMC films was initially increased in the presence of talc because of a stronger film-tablet
interface and a smaller increase in the internal stress of the film, but above 10% by weight of the
pigment, the internal stress factor began to dominate and adhesion fell.
In a large comparative study (Gibson et al., 1988), the effect of the iron oxide pigments titanium
dioxide, talc, erythrosine lake, and sunset yellow lake were examined upon HPMC (Pharmacoat 606)
films plasticized with PEG 200. The authors concluded that the Young’s modulus of the films is raised
by the pigments to an extent that largely depends upon pigment shape and can be predicted by existing
theories. The exceptions are titanium dioxide and the lake pigments which have less of an effect on the
modulus than expected due to polymer-pigment interactions or, in the case of the lake pigments, to a
loose particle structure. The ultimate tensile properties of the films depend mainly on the concentration
of the particles added. Pigments cause a large decrease in tensile strength except in the cases of yellow
or black iron oxides which are not weakened to such an extent because the shape of the particles allows
the growth of flaws to be retarded. If the thermal expansion coefficients of the matrix and filler promote
premature cracking on cooling from the fabrication temperature, then the introduction of filler in any
concentration is detrimental to the tensile strength of the system.

2.9 SOLVENTS/VEHICLES

These materials perform a necessary function in that they provide the means of conveying the coating
materials to the surface of the tablet or particle. The major classes of solvents capable of being used are:
• water
• alcohols
• ketones
A prerequisite for a solvent would be that it has to interact well with the chosen polymer; this is
needed as high polymer solvent interaction permits film properties such as adhesion and mechanical
strength to be optimized. Selection of the correct solvent can be predicted by a thermodynamic approach
as described in section 2.7.5.
Kent & Rowe (1978) utilized the solubility parameter approach in evaluating the use of ethylcellulose
in various solvents for film coating. By evaluating the effect of solubility parameter on intrinsic
viscosity for a range of solvents graded as to the extent of hydrogen bonding, they were able to
determine not only which was the best class of solvent to use but also what was the optimum solvent
solubility parameter. Rowe (1986) has pointed out that ideally for this use the solubility parameter needs
modification to take into account components due to van der Waals’ forces, hydrogen bonding and
polarity. Thus, using a modification proposed by Hansen (1967), Rowe has produced solubility
parameter maps to evaluate the compatibility of ethylcellulose in admixture with methylcellulose and
HPMC.
Considering polymer solvents in a wider sense, a thermodynamically based compatibility is not the
only practical requirement. Kinetic considerations of the ability of the solvent to penetrate the polymer
mass effectively and solvate the polymer in such a way that polymer swelling and dissolution take place
effectively are also very important. Thermodynamically good solvents do not always make kinetically
good solvents, and vice-versa. Hence the choice of a suitable solvent selected on the above criteria is
likely to be a process of compromise.
Another practical feature is that the chosen solvent should not pose volatility problems. Besides
causing processing difficulties, the controlled deposition of coating materials to form a coherent film
coat could be compromised.
The use of solvent mixtures should be fully validated. The problem here is that during the coating
process preferential evaporation of solvents from the mixture is liable to take place (unless, of course, a
constant boiling mixture is used). An extreme example would be that as a result, polymer precipitation
would occur with no film-formation. At the least, polymer solubility could be affected to the extent that
film-forming ability would suffer. This problem has been described by Spitael & Kinget (1977) in
considering the effect of processing solvent on the film-forming property of cellulose acetate phthalate.
Using three different methods of preparing films they demonstrated that entire films were formed only
with certain solvents or combinations. For example, only two solvents gave consistently good results,
namely acetone and the azeotropic mixture of 77% ethyl acetate and 23% isopropanol. The other
solvents, which were 1:1 mixtures of ethyl acetate with isopropanol and acetone with ethanol, gave
opaque, brittle films which lacked cohe-siveness. Less than optimal film-forming conditions for a
functional film such as this would have serious consequences.
• esters
• chlorinated hydrocarbons.
A prerequisite for a solvent would be that it has to interact well with the chosen polymer; this is
needed as high polymer solvent interaction permits film properties such as adhesion and mechanical
strength to be optimized. Selection of the correct solvent can be predicted by a thermodynamic approach
.
Kent & Rowe (1978) utilized the solubility parameter approach in evaluating the use of ethylcellulose
in various solvents for film coating. By evaluating the effect of solubility parameter on intrinsic
viscosity for a range of solvents graded as to the extent of hydrogen bonding, they were able to
determine not only which was the best class of solvent to use but also what was the optimum solvent
solubility parameter. Rowe (1986) has pointed out that ideally for this use the solubility parameter needs
modification to take into account components due to van der Waals’ forces, hydrogen bonding and
polarity. Thus, using a modification proposed by Hansen (1967), Rowe has produced solubility
parameter maps to evaluate the compatibility of ethylcellulose in admixture with methylcellulose and
HPMC.
Considering polymer solvents in a wider sense, a thermodynamically based compatibility is not the
only practical requirement. Kinetic considerations of the ability of the solvent to penetrate the polymer
mass effectively and solvate the polymer in such a way that polymer swelling and dissolution take place
effectively are also very important. Thermodynamically good solvents do not always make kinetically
good solvents, and vice-versa. Hence the choice of a suitable solvent selected on the above criteria is
likely to be a process of compromise.
Another practical feature is that the chosen solvent should not pose volatility problems. Besides
causing processing difficulties, the controlled deposition of coating materials to form a coherent film
coat could be compromised.
The use of solvent mixtures should be fully validated. The problem here is that during the coating
process preferential evaporation of solvents from the mixture is liable to take place (unless, of course, a
constant boiling mixture is used). An extreme example would be that as a result, polymer precipitation
would occur with no film-formation. At the least, polymer solubility could be affected to the extent that
film-forming ability would suffer. This problem has been described by Spitael & Kinget (1977) in
considering the effect of processing solvent on the film-forming property of cellulose acetate phthalate.
Using three different methods of preparing films they demonstrated that entire films were formed only
with certain solvents or combinations. For example, only two solvents gave consistently good results,
namely acetone and the azeotropic mixture of 77% ethyl acetate and 23% isopropanol. The other
solvents, which were 1:1 mixtures of ethyl acetate with isopropanol and acetone with ethanol, gave
opaque, brittle films which lacked cohe-siveness. Less than optimal film-forming conditions for a
functional film such as this would have serious consequences.

2.10 AUXILIARY SUBSTANCES IN THE FILM-COATING FORMULAE

Mention has already been made of the occasional addition of substances such as flavours and waxes to
film-coating formulae. In recent times there has emerged a new class of auxiliary substances which,
when combined with the traditional ingredients of a film-coating formula, show advantageous properties. These are saccha-ride materals such as
polydextrose, maltodextrin and lactose. Perhaps their most remarkable property is to increase the
adhesion of cellulosic systems to substrates. Jordan et al. (1992) have quoted examples where lactose-
HPMC combinations under defined conditions demonstrated an adhesive force of 40 kN/m2 for a waxy
tablet core where an HPMC-HPC combination measured only 26 kN/m2 and a simple HPMC coating
failed to show any measurable adhesion to the core. These saccharide-cellulosic combinations have also
been shown to improve the stability towards light of several unstable colours used as film-coating
colourants. As yet, the mechanism of action of these auxiliary materials is not totally understood.

2.11 THE CHOICE BETWEEN AQUEOUS AND ORGANIC SOLVENT-BASED

COATING

Since the 1970s there has been a steady move away from the originally used organic solvents to the use
of water as the coating medium (Hogan, 1982). The reasons for this change are not hard to find.
Considerations of environmental pollution enforced by local legislation have made it impossible to
operate in the same manner as in the early days of the technology. This, coupled with safety and healthrelated
issues of people in the workplace, has meant that there is an increasing number of companies
who are willing to consider aqueous processing. Only since the advent of the aqueous dispersed forms
of the original acrylic polymers has it been possible to utilize aqueous processing for these materials.
However, the commonly used cellulosic polymers, with the exception of ethylcellulose, have an
appreciable water solubility which has always made them theoretically available for aqueous processing.
It must be remembered that in the early 1970s the sophistication of processing equipment was inferior
to the situation today. In particular, drying ability was defi-cient, thus placing a necessary emphasis on
the use of as low a boiling point solvent as practically possible. In addition, the cellulose derivatives in
common use, although water soluble, were not ideally suited to aqueous use as the grades available had
an excessively high viscosity in water, thus rendering their solutions difficult to atomize.
Gradually the introduction of new purpose-built coating equipment and lower viscosity cellulosic
polymers enabled the interest in aqueous processing to be translated into activity. During this period
several of the misconceptions of aqueous processing were removed from the minds of workers in this
area—notably that aqueous processing would mean overly long coating processes or that the use of
water was bound to pose severe stability problems. As a generalization there are very few tablet
formulations that cannot be aqueously film coated (Tonadachie et al., 1977). It is also true to say that the
requirement for water-based processing is now so strong in certain parts of the world that film-coating
systems and polymers are specifically designed with this requirement in mind. For modified release
coatings, where water-insoluble polymers have traditionally been used, special water-dispersible forms
have been developed by manufacturers.







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