You are on page 1of 12

See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/263725433

Film Coating Technology: Past, Present and Future

Article · March 2014


DOI: 10.1166/jpsp.2014.1007

CITATIONS READS
2 5,161

5 authors, including:

Alok Pratap Singh Mohd Yasir


I.T.S. Pharmacy College I.T.S. Pharmacy College
6 PUBLICATIONS   63 CITATIONS    32 PUBLICATIONS   270 CITATIONS   

SEE PROFILE SEE PROFILE

Some of the authors of this publication are also working on these related projects:

Preformulation studies View project

All content following this page was uploaded by Mohd Yasir on 26 January 2015.

The user has requested enhancement of the downloaded file.


Article
Journal of
Pharmaceutical Sciences
and Pharmacology
Copyright © 2014 American Scientific Publishers
All rights reserved Vol. 1, 57–67, 2014
Printed in the United States of America www.aspbs.com/jpsp

Film Coating Technology: Past, Present and Future


Praveen Kumar Gaur1 ∗ , Shikha Mishra2 , Rohit Gautam1 , Alok Pratap Singh1 , and Mohd Yasir1
1
Department of Pharmaceutics, I.T.S. Paramedical College (Pharmacy), Muradnagar, Ghaziabad, U.P. 201206, India
2
Department of Pharmacognosy and Phytochemistry, Jamia Hamdard, New Delhi 110062, India

Film coating has evolved with time keeping in pace with the demands of the Pharmaceutical industry. There has been
tremendous and necessary modification like improved production equipment and the development of highly efficient film-
coating formulations and polymers which has accelerated the acceptance of film-coating technology. Film coating has
taken over sugar coating owing to the broader flexibility and additional functionalities in former. There has been state
of the art level improvisation in methodology and technique exemplified by solvent or water based and dry coating. The
main focus of this literature review is to summon up the different types of coating technologies and various parameters
and variables that play a major role during the entire process. Commentary on future direction is also provided.
KEYWORDS: Film Coating, Aqueous Coating, Dry Coating, Process Parameters.

INTRODUCTION pump, pulsatile


Delivered by Publishing Technology delivery,
to: Guest Userthereby improving upon bioavail-
IP: 162.218.208.135
Each drug has its own characteristics, like bitterness, On: Tue, 14
abilityOct
and 2014 14:24:21
therapeutic potential of a drug. On a different
Copyright: American
unpleasant odour, lightsensitivity or hygroscopicity. Tablet Scientific
note, Publishers
coating reduces friction and increases packaging rate
coating was done to solve such problems in conventional (Lachman et al., 1989; Libermen and Lachman, 2003).
dosage form. Previously, sugar coating was mostly applied
to achieve this purpose. But it was skilled manipulative and BASIC PRINCIPLE INVOLVED IN
time consuming process that could last for even five days so TABLET COATING
it got replaced by film coating (Porter, 2011). The operator
Coating may be applied to a wide range of oral solid
had to be highly skilled for such coating. Hence film coat-
dosage forms, including tablets, capsules, multi partic-
ing was preferred and eventually it replaced sugar coating. ulates and drug crystals by applying spray-atomisation
The current drugs are diverse in chemical nature as well technique. Primary components involved in tablet coating
as in physical attributes. It can give a bitter taste in the are properties of tablet, processing variables, equipments,
mouth or has an unpleasant odour. Such properties can be ancillary equipments and automation in coating processes
appropriated by using coating technology which can in turn e.g., coating process design and control. Usually, the coat-
improve the patient compliance (Fig. 1). Further the core ing mixture is sprayed through a nozzle onto the tablets as
may contain a substance which is light sensitive or affected the tablets are being agitated in a pan or fluid bed. A film
by oxidation so coating can be added to improve stabil- of coating liquid is formed on tablet surface as the coating
ity by acting as a physical barrier to environmental storage mixture is sprayed. This film can be formed with a single
conditions. The coating develops the mechanical integrity application or through multiple spraying in a batch pro-
which means coated products are more resistant to mishan- cess consisting batch identification and formula selection,
dling (abrasion, attrition etc.). It also improves the appear- loading, heating, spraying, cooling and drying (Libermen
ance and creates a unique look for identification. The major and Lachman, 2003).
attribute of coating is modulation of release profile e.g.,
extended release, enteric coating (delayed release), osmotic
CLASSIFICATION

Organic Solvent Based
Author to whom correspondence should be addressed.
Email: gaurmpharma@rediffmail.com In the early 1950s, film coating was performed by applying
Received: 15 September 2013 the polymers dissolved in organic solvents which provided
Accepted: 25 October 2013 several benefits over sugar coating such as less processing

J. Pharm. Sci. Pharmacol. 2014, Vol. 1, No. 1 2333-3715/2014/1/057/011 doi:10.1166/jpsp.2014.1007 57


Film Coating Technology: Past, Present and Future Gaur et al.

Delivered by Publishing Technology to: Guest User


IP: 162.218.208.135 On: Tue, 14 Oct 2014 14:24:21
Copyright: American Scientific Publishers

Figure 1. Chronological development (Decade wise) in coating technology.

time, possibility of preparing thin smooth continuous coat- Dispersions


ings and reduced risk of hydrolysis (Fig. 2). Recently, aqueous polymer dispersions are being used
The film formation occurs due to removal of the sol- in coating of water-insoluble polymers due to increas-
vent causing an increase in concentration of polymer ing concerns about the toxicity of the organic solvents,
resembling a gel. However, coating with organic solutions environmental pollution and cost-intensive solvent recov-
decreased in popularity due to the restrictions concerning ery systems. The size of the polymer particles in these
hazardous solvents. On the other hand, environmental con- two-phase systems is in the colloidal range, with the upper
cerns and regulatory issues enhanced the production costs, limit around 1 m, to ensure good storage stability. The
due to solvent recovery (Savage and Rhodes, 1995). main property of these dispersions is their low viscosity
despite their high solids content, which may reach up to
Aqueous Based Coating 30% of the total formulation (Dillon et al., 1951).
The major problem related to aqueous coating systems
Solutions
is prolonged processing time due to the higher heat of
Primary requirement for the polymer is to be water solu- vaporization of water however this problem was eradi-
ble. These systems have been used as protective coatings cated by modified equipment design such as development
as they result in water-soluble films without any release of side-vented perforated coating pans and fluidized bed
modifying effects. Commonly used hydrophilic polymers equipment for increased drying efficiency. Process automa-
are cellulose derivatives such as HPMC however PVP, tion and the concept of validation have resulted in a strong
PVA and PEGs are also suitable. Small molecular weight increase of productivity. The film formation from aque-
polymers are favoured to optimize the ratio of solid con- ous colloidal dispersions is a complex, multi-step process.
tent to viscosity for the coating formulation. Optimal inter- The polymer particles are closely packed upon increasing
action of the polymer can be obtained by the use of concentration of the dispersion due to water evaporation.
water-soluble plasticisers e.g., glycerol, propylene glycol In this ordered arrangement the polymer particles come
or triacetin (Lehmann, 1994; Porter, 1990). into contact with each other for the first time. Further

58 J. Pharm. Sci. Pharmacol. 1, 57–67, 2014


Gaur et al. Film Coating Technology: Past, Present and Future

formation the individual particles lose their identity after


the diffusion of polymer chains through the boundary and
formation of a continuous film with adequate mechanical
properties occurs. The performance of the resulting film is
highly affected by the temperature during film formation.
If the temperature remains above the boiling temperature
of water the vapour pressure during film-formation may
be sufficient to burst the surface film layer causing voids
and pinholes. These imperfections may be responsible for
higher water vapour permeability or enhanced drug release
(Harris and Sellassie, 1997).

Redispersible Powders
These systems were originally developed for enteric poly-
mers which were esters, prone to hydrolysis in aque-
ous media (Porter, 1990). e.g., Aquateric, the commercial
redispersible powder of cellulose acetate phthalate (CAP),
or redispersible Eudragit L, enteric variant of methacrylic
acid copolymer (Bodmeier and Paeratakul, 1994). Addi-
tional advantages of redispersible powder formulations are
less propensity for flocculation when exposed to high shear
forces or temperature changes, reduced storage and ship-
ping cost and enhanced microbiological stability. Redis-
persible polymer powders are usually prepared through
freeze- or spray drying of polymer dispersions. But, it is
important that the properties of the original polymer dis-
persions are
Delivered by Publishing Technology to:regained after the redispersion of the polymer
Guest User
IP: 162.218.208.135 On: Tue,powder
14 Oct especially the original particle size distribution
2014 14:24:21
Copyright: American Scientific
since an Publishers
increase in the particle size can affect the film
formation negatively.
The film formation from aqueous dispersion occurs by
coalescence of particles in a continuous film (Fig. 3). The
coalescence of aqueous polymer dispersion is initiated by
water evaporation which pushes dispersed polymer parti-
cles into a closely packed, ordered array with water filled
voids. After the polymer particles come into contact with
each other, they deform and fuse in order to coalesce into
a film. Coalescence occurs when the promoting forces are
greater than the resistive forces of the particles. Film forma-
tion, i.e., coalescence, is a complex process and depends on
coating and storage conditions, coating polymer, polymer

Aqueous dispersion of coating material deposited


on the surface of the tablet

Water vaporization

Compaction and deformation of coating material


on the surface of the tablet
Figure 2. Types of film coating.
Water vaporization

water loss goes along with a deformation of the particles Coalescence of coating material on the surface of
the tabletand form a film
forming a denser array (Cole, 1998). Dry sintering and
capillary forces are considered as possible mechanisms for Figure 3. Mechanism of aqueous polymer film formation
the particle deformation. Finally, in the last stage of film process.

J. Pharm. Sci. Pharmacol. 1, 57–67, 2014 59


Film Coating Technology: Past, Present and Future Gaur et al.

molecular weight and particle size, coating liquid con- deeply influenced. A biconvex, round tablet is preferred as
stituents and properties like viscosity and surface. Since flat tablets tend to agglomerate during the process. There
coalescence occurs above a minimum film formation tem- are possibilities of shallow convex tablets undergoing abra-
perature (MFT), temperature and rate of water evaporation sion due to its sharp edges and thus sub-coating becomes
are major process-related factors affecting the properties of essential.
coatings. Usually, a thermal after-treatment (curing) is done Surface wettability is important, as wetting and spread-
to remove the film defects (Aulton, 1995; Lachman et al., ing of the polymer material is related to the smoothness of
1989). the film and adhesion to the substrate. Coated multipartic-
ulate systems offer several advantages over larger, single
Process Parameters unit dosage forms, especially when applied to modified-
The spraying rate affects the moisture content which in release coatings, due to greater uniformity in GI transit
turn affects quality and uniformity of the film. A low spray time and a reduced potential for premature release. These
rate will give a brittle film due to incomplete coalescence coated particles can be filled into capsules or compressed
due to inadequate wetting and a high spray rate causes into tablets. When compressing coated particles, the force
over wetting resulting in picking and sticking. The spray used during the tabletting process and the mechanical
rate also interacts with tablet temperature and a low tablet strength of the coating are critical. Faster drug release may
temperature with high spray rate can produce cracks in occur if the film cracks or fractures during compaction,
the film. Increase in pressure reduces the surface rough- while slower drug release has been reported when the coat-
ness by producing thin dense film however excessive pres- ings fuse together to form a matrix. Excipients, such as
sure forms very fine droplets which spray dries before microcrystalline cellulose, minimize direct contact of the
getting to tablet bed causing spray loss. The inlet air tem- coated pellets and dissipate the compression forces to pre-
perature impacts the drying process and coating unifor- vent film fracture.
mity. High temperature enhances the drying efficiency and Polymeric films adhere to the substrate surface using
decreases the water penetration however too much air tem- two major forces namely the strength of the interfa-
perature can cause premature drying and reduces the effi- cial bonds and the internal stresses within the film. The
ciency. Since water is less volatile than organic solvents primary type of interfacial bonding is hydrogen bond for-
and requires higher drying capacity resulting in higher mation, although dipole and dipole-induced dipole interac-
energy cost of the entire coatingDelivered by Publishing
process. Ideal Cures Pvt. Technology
tions
to: Guest User
IP: 162.218.208.135 On: Tue, 14 also occur.14:24:21
Oct 2014 Substrate considerations, such as surface
Ltd. has developed some products (INSTACOAT range roughness, tablet
Copyright: American Scientific Publishers hardness and substrate hydrophobicity
for example Instacoat EHP 250, Instacoat EMB, Instacoat can affect the strength of interfacial bonding. In contrast,
EEN, Instacoat EHA, Instacoat Aqua, Instacoat Aqua II, internal stresses, which arise from forces due to shrinkage
Instacoat Aqua III and Instacoat P4) which dries faster and of the film upon solvent evaporation, thermal stress due to
the whole coating process can be completed in the same the differences in thermal expansion of the film and the
or sometimes little less time as compared to organic sol- substrate and volumetric stress due to swelling during stor-
vent based coatings. The increase in rotating speed can age, tend to weaken adhesion. Use of excipients with ther-
improve the mixing but to a certain level. An increase in mal expansion coefficients similar to that of the polymer
the pan speed reduces variation in thickness and enhances can reduce internal stresses and improve polymer adhesion
the coating uniformity however a excessively high speed (Lippold and Monells, 2001; Okutgen et al., 1991; Franz
can lead to undesired breakage. and Doonan, 1983).

Air Pressure of Atomisation Dry Coating


Usually, the drug should be stable to withstand all the pro- There are several disadvantages of using the solvents
cessing parameters as per the specification however it is whether aqueous or organic e.g., drying time and microbi-
important to consider the properties of the drug. There is a ological stability for aqueous coating whereas safety and
strong potential of interaction that can occur between the environment hazards for organic solvents. These issues
drug and polymeric material or any other additive. Poly- have led to the adoption of dry powder coating techniques
meric material after atomisation can possibly dissolve the in a number of other industries. Among these are technolo-
outer layer of the substrate and the components of the lat- gies which range from the atomization of molten materials,
ter may also migrate e.g., migration and subsequent recrys- commonly known as melt coating, to softened powder lay-
tallization of propranolol HCl in Eudragit NE 30D films ering and electrostatic adhesion. Types of Dry Coating are
so sub-coating is done to overcome this problem as it pre- as follows (Felton and Porter, 2013):
vents interactions and it is suitable when enteric coating
is being done on an acid-labile drug as enteric coating Electrostatic Dry Coating
polymers are acidic in nature (Rekhi et al., 1995). This novel coating technique is an alternative to aqueous
Size and shape of the substrate is also of consider- or solvent based coating process is widely useful in food
able importance as its movement within the equipment is technology, paint technology, metal coatings, coating of

60 J. Pharm. Sci. Pharmacol. 1, 57–67, 2014


Gaur et al. Film Coating Technology: Past, Present and Future

living cells and coating of tablets as well as capsules. The (ii) Levelling of the coating material includes densifica-
principle of electrostatic powder coating states that spray- tion of the layer with reduction of the empty spaces and
ing of a mixture of finely grounded particles and polymers smoothening of the surface;
onto a substrate surface without using any solvent and then (iii) Cooling of the layer and hardening of the coating.
heating the substrate for curing in oven until the powder
mixture is fused into film.
Based on Function
According to the charging mechanism, there are two
Protective Coatings
types of spraying units namely
(a) Corona charging Thin films of water soluble polymers are often applied
(b) Tribo charging. for taste or odour masking or to improve the stability
of moisture sensitive products or for better mechanical
Magnetically Assisted Impaction Coating resistance of the product during handling. Such protective
coatings need to remain intact for the short time of swal-
In this technique the particles are assumed to stay in a
lowing and after that they should immediately dissolve to
fluidized state where the distribution of velocities is a
ensure immediate drug release. These polymers are water-
Maxwell–Boltzmann type. It is assumed that the collisions
soluble, e.g., cellulose ethers (e.g., hydroxypropyl methyl-
occurring among the particles are important for impinging
cellulose (HPMC)), polyvinyl acetate (PVA) or polyvinyl
the guest particles onto the surface of host particles thereby
pyrrolidone (PVP). Eudragit® E is a methacrylic copoly-
making a transient surface on the host particles. The coating
mer, insoluble in saliva, but rapidly dissolves in the acidic
time depends on various parameters e.g., properties of the
pH of the stomach. Sometimes enteric polymers, e.g., shel-
host and guest particles, number of host particles, height of
lac can also be applied at very low concentration which
the fluidized bed and ratio of the host and guest particles
gives very low film thickness insufficient to provide gastric
diameters. For a particular coating time, the bed height and
particle size should be optimum (Singh et al., 2001). resistance and disintegrates in the stomach within 30 min
(Lehmann, 1994; Porter, 1990; Porter, 2011).
Film Formation Mechanisms in
Dry Powder Coating Functional Coatings
Film formation takes place by a process of evaporation, Film coatings, which are applied to achieve a desired
coalescence and sintering whichDelivered by Publishing
are influenced by pro- Technology to: Guest
release profile, are User
usually termed modified-release or
IP: 162.218.208.135 On: Tue, 14 Oct 2014
functional 14:24:21
coatings. Those, intended to protect the drug
cess and formulation considerations. During the dry pow-
Copyright: American Scientific Publishers
der coating process, the substrates are often heated above from the acidic environment of the stomach are enteric
the glass transition temperature of the layering materials coatings. Extended release coatings, in contrast, are
so that the coating materials soften and adhere to the sub- intended to control the release of the drug over a prolonged
strate. For conventional film coating, spreading and adher- period of time (Porter, 1990).
ence is not limited by mobility however, powder systems Enteric Coatings. Enteric coatings are prepared from
may become limited by mobility, particularly when liquid gastric resistant polymers which remain intact in stom-
levels are reduced to the point where solid particle defor- ach, but immediately dissolve in small intestine. The
mation becomes rate limiting. This introduces a series of most effective enteric polymers contain many carboxylic
constraints related to mechanical and thermal properties groups with a pKa of 3–5. Therefore they will dissoci-
of the coating formulation. Coalescence and film forma- ate and dissolve only when the pH rises above this value
tion are therefore dependent on these properties as well. (Porter, 2011; Lehmann, 1994). Before the synthetic poly-
As such, glass transition temperature and plastic deforma- mers were introduced to the market, shellac, a natural
tion characteristics of the coating materials are paramount polymer, was one of the main polymer used for this pur-
to the success of the process. Many pharmaceutical coat- pose. Cellulose acetate phthalate (CAP) was the first syn-
ing materials are amorphous polymers, exhibiting a glass thetic polymer described in 1937, which soon gained high
transition temperature related to the change from a glass popularity as a gastric resistant polymer. Later polyvinyl
to a super cooled liquid. On transition, which occurs at a acetate phthalate (PVAP) and hydroxypropyl methylcel-
specific temperature, mobility of the system increases sig- lulose phthalate (HPMCP) were preferred, due to their
nificantly. The greater mobility allows for molecular rear- lower permeability in the gastric fluid and improved sta-
rangement and alters the plastic deformation characteristics bility against hydrolysis. Today methacrylate copolymers
of the materials. Eudragit® L and S are two of the most widely used poly-
The mechanism of film formation of the powders lay- mers for this purpose (Malm and Waring, 1937; Zheng and
ered onto the solid cores is—summarized as (Felton and McGinity, 2003).
Porter, 2013; Felton, 2007): Extended Release Coatings. The patient compliance is
(i) Coalescence and sintering of the particles of the poly- usually inversely proportional with the frequency of drug
meric materials in a process that involves the partial fusion administration especially when multiple daily administra-
of the polymer; tions are necessary to maintain constant blood levels of the

J. Pharm. Sci. Pharmacol. 1, 57–67, 2014 61


Film Coating Technology: Past, Present and Future Gaur et al.

drug. Therefore, extended release polymers were devel- correlation between coating parameters and content unifor-
oped, which are able to provide a sustained action by a mity but the model proposed by Cheng et al. has confirmed
controlled release over time. Waxes and some natural poly- to be most robust (Chen et al., 2010; Chen et al., 2008).
mers were already discovered earlier to be useful to pro- Coating time is also an important parameter since a
long the drug release if coated onto the solid dosage forms. longer coating time results in better content uniformity but
Mostly their mechanism of performance is based on slow it makes the process not amenable for a high volume prod-
degradation or erosion. Polymers for extended release are uct. On the other hand, too short coating time can lead to
in general insoluble in water over the entire pH range. The incomplete coating process. Spray zone width should not
drug release is thus controlled by diffusion through the be too narrow or too wide. If the tablet bed has not been
hydrated polymer or through cracks or water-filled pores. appropriately covered then there will be either unsprayed
There are still only few polymers available on the mar- substrate or unused deposit of coating solution.
ket for extended release, e.g., cellulose acetate, ethylcel- Coating process should yield the tablets having required
lulose or the methacrylic acid copolymers Eudragit® RS, polymorphic forms and the coating suspension should
RL and NE. Combinations of ethylcellulose with waxes, crystallise after drying. The stability is adversely affected
water-soluble or enteric polymers were investigated to if the coating stays in amorphous state. The polymor-
achieve extended drug release for drug with varying or phism also depends on coating excipients e.g., plasticisers
even pH-dependent solubilities. Synthetic polymers, how- (Narang et al., 2011; Narang et al., 2012; Chen et al., 2010;
ever, do not fit into the overall product concept of phyto- Chen et al., 2008).
pharmaceutical products, or as for nutraceuticals they are Effectiveness of the Active Coating Process. The coat-
not approved. Therefore several attempts were undertaken ing efficiency improves significantly when the droplet size
to achieve sustained drug release by using only natural is smaller than 10 m. By appropriate selection of atomiz-
polymers. The drug release from silk fibroin coated tablets ing and pattern air volume, the fraction of droplets smaller
after cross-linking with a carbodiimide was extended to than 10 microns can be reduced to improve the overall
several hours (Savage and Rhodes, 1995). Shellac is also efficiency of the coating process. Factors governing them
able to provide prolonged drug release at higher coating such as high ratios of the suspension spray rate to atom-
levels or as matrix forming material. However, there is no ization air flow rate, suspension spray rate to pattern air
drug release for such systems in the gastric medium due to flow rate, or atomization air flow rate to pattern air flow
the enteric property of shellac. Delivered by Publishing Technology
Zein as a water-insoluble to: Guest
rate can improve theUser
coating efficiency.
IP: 162.218.208.135 On: Tue, 14 Oct 2014 14:24:21
natural polymer is an alternative for extended drug release,
Copyright: American Scientific Publishers
especially in combination with an additional enteric top-
coat (Mazer et al., 1992).
FILM COATING FORMULATION
COMPONENTS
Polymers
Active Coating
In it, the drug is embedded into the coat to formulate a A polymer is a large molecules made up of many identical
fixed dose combination or to modify the release profile. subunits of monomers (Table I).
The beadlets are then filled into capsules however the vol-
ume limitation of capsules makes it an unsuitable approach Immediate Release Coating Polymers
for higher dose drugs (Seitz et al., 1988). Cellulose Derivates. The most widely used cellulosic
This is particularly useful for the drugs unstable at polymers is Hydroxypropyl Methyl Cellulose (HPMC)
high mechanical stress. In an active coating process, com- which is readily soluble in aqueous medium and forms flex-
mon pharmaceutical operations can be avoided. Drugs that ible strong films which adhere to the core. Other examples:
undergo acid or base catalysed degradation have been sta- MC (Methyl Cellulose) and HPC (Hydroxypropyl Cellu-
bilized by this technique. It gives relatively high drug to lose) (Hogan, 1998; Lachman et al., 1989; Lehmann, 1994).
excipient ratio than encapsulating such molecules in the Vinyl Derivates. The most widely used vinyl polymer
tablet core. Fixed dose combinations can be formulated by is Poly Vinyl Pyrrolidone (PVP) however it has inherent
this approach (Hogan, 1998). tackiness. For better film coating, its copolymer with vinyl
The primary concerns of an active coating process acetate is used.
are end-point, content uniformity, efficiency and stability
which are either directly or indirectly affected by pro- Modified Release Coating Polymers
cess parameters such as rate of spraying, inlet air temper- Extended Release Coating Polymers. They are dis-
ature, residual moisture, pan speed, atomisation pressure solved in organic solvent or dispersed in aqueous medium
and drug properties. The end point is estimated by the gain e.g., highly substituted cellulose making them water-
in tablet weight or quantity of coating suspension sprayed. insoluble, example: Ethyl Cellulose (EC).
Periodically, tablets are sampled and analysed for the drug Enteric Coating Polymers.
amount (Lipper et al., September 11–12, 2006). Several (a) Methacrylic Acid. The presence of carboxylic acid
mathematical models have been proposed to ascertain a groups renders this class to be insoluble in water at low pH

62 J. Pharm. Sci. Pharmacol. 1, 57–67, 2014


Gaur et al. Film Coating Technology: Past, Present and Future

Table I. Film coatings are available based on the following polymeric materials.

S. no Polymer Trade name Functions

Cellulose-based coatings
1. Cellulose Acetate Phthalate Aquacoat CPD® , C–A–P NF Enteric coating
(CAP) Eastman
2. Hydroxypropylmethylcellulose Sepifilm™LP Immediate release
(HPMC)
3. Hydroxypropylcellulose (HPC) Klucel® Polymer extender, subcoat
4. Ethylcellulose Aquacoat® ECD, Aqualon® , Immediate release, taste
Surelease® masking, sustained release
5. Methylcellulose Metolose® SM-4 Taste masking, pellet coating
6. Microcrystalline cellulose and LustreClear™ Taste masking
carrageenan
Methacrylate based coating
1. Anionic polymer of methacrylic Eudragit® L 100-55, Eudragit® S Enteric coating
acid and methacrylates with a 100, Eudragit® L 30 D-55
–COOH group Eudragit® L 100, Eudragit® FS 30
2. Cationic polymer with a Eudragit® E PO and Eudragit E 100
dimethylaminoethyl ammonium
group
3. Copolymers of acrylate and Insoluble, High permeability Sustained release
methacrylates with quarternary Eudragit® RL PO, Eudragit® RL
ammonium group. and Eudragit® RL 30D Insoluble,
Low Permeability Eudragit® RS
PO and Eudragit® RS 30D
4. Copolymers of acrylate and Eudragit RD 100 Rapidly disintegrating
methacrylates with quarternary
ammonium group in
combination with sodium
carboxymethylcellulose
Delivered by Publishing Technology to: Guest User
IP: 162.218.208.135 On:based
Shellac Tue, coating
14 Oct 2014 14:24:21
1. Shellac Copyright: American Scientific
EmCoat 120 N Publishers Enteric coating
2. Shellac MarCoat 125 Taste Masking, enteric coating
pH Independent polymer for rapidly disintegrating film coating
1. Neutral co-polymer Film coat E30D For film coating of tablets,
pellets, granules, powders.
Natural polymer
1. Xanthan gum Film coating of tablets
2. Pectin Film coating of tablets
3. Chitosan Film coating of tablets
4. Okra gum Film coating of tablets
5. Grewia gum Film coating of tablets

(stomach) but as the pH rises towards neutrality in upper • Cellulose acetate trimellitate (CAT)
part of the small intestine the coating gradually dissolves. • Cellulose acetate succinate
Example: Eudragit. • Hydroxypropylmethylcellulose acetate succinate (HPM-
(b) Phthalate esters. These polymers contain free car- CAS)/hypromellose acetate succinate
boxylic acid, making them acid insoluble however in intes- • Hydroxypropyl methylcellulose phthalate.
tine they become deprotonated and dissolves in basic Polyvinyl derivatives
media. They are also called enteric coating polymers e.g., • Polyvinyl acetate phthalate (PVAP).
Cellulose acetate phthalate (CAP). Enteric coating poly-
mers can be classified into 3 groups based on chemical The solubility of the polymers depend on the number
compositions as listed below: of carboxylic acid groups. Enteric formulations should
have less than 10% drug release in 2 hours during acid
Polymethacrylates
stage. The completion of the drug release in the continu-
• Methacrylic acid/ethyl acrylate
ation testing in the buffer stage should take place within
• Cellulose acetate phthalate (CAP) 45 min. Classification of Polymers Based on Derivatives
Cellulose esters (Lehmann, 1994; Libermen and Lachman, 2003; Malm

J. Pharm. Sci. Pharmacol. 1, 57–67, 2014 63


Film Coating Technology: Past, Present and Future Gaur et al.

and Waring, 1937; Sadeghi et al., 2001; Ogaji and Nnoli, oxides are most commonly used pigments. Colour migra-
2010; Ogaji and Hoag, 2011; Ogaji et al., 2013). tion and stability issues have diminished the use of the
water-soluble dyes in film coating. Pigments can signifi-
Plasticizers cantly affect the mechanical and permeability properties of
Plasticizers are relatively low molecular weight materials the film. An inverse relation-ship between film-tablet adhe-
which are used as additives in pharmaceutical coating for- sion and the particle size of the pigment has been reported.
mulations to reduce the brittleness and increase the flex- Studies have shown that the shape of the pigment par-
ibility of the resulting film. They act by weakening inter ticle and the extent of polymer-particle interaction influ-
molecular attraction between polymer chains and facili- ence the elastic modulus of polymeric films and surface
tating coalescence of discrete polymer spheres of aque- polarity of pigments influences drug release. In addition
ous dispersed systems during film formation. Adhesive and chemical incompatibilities between the pigment and the
mechanical properties of the coating and subsequent drug polymer have also been reported, predominantly related
release are dependent on the concentration of plasticizers to the size and surface charge of the components and
to a great extent. Plasticizers are non volatile components the pH of the medium. One important concept relevant
and therefore are responsible for the weight gain of dosage to pigments is the critical pigment volume concentration
forms during coating. A plasticizer has to be miscible and (CPVC); this is the maximum concentration (based on vol-
fulfil all the compatibility parameters with the polymer ume) of the insoluble material that can be incorporated into
being used. a film without compromising film properties. If the CPVC
An important consideration is the content of plasticizer is exceeded, insufficient polymer is present to surround
as it can affect the glass transition temperature (Tg ) so all the insoluble particles, resulting in marked changes in
it should be experimentally determined by evaluating the different properties of the film. Colorants are mainly clas-
changes in Tg of polymer as the plasticizer content is sified in to three types:
increased. Tg is the temperature for amorphous polymers (i) Organic dyes and their lakes e.g., Erythrosine, tar-
at which the behaviour of the film changes from hard and trazine, Sunset yellow.
brittle to soft and elastic. An effective plasticizing agent (ii) Inorganic colours e.g., Iron oxide yellow, red and
is one which exhibits a greater decrease in the Tg of the black, titanium dioxide, talc.
film. Changes in the mechanical Delivered
propertiesbyofPublishing
the poly- Technology to: Guest
(iii) Natural coloursUser
e.g., Riboflavin, Anthocyanins, and
meric film are an indication ofIP: 162.218.208.135
plasticizer On: Tue,
efficacy (Seitz 14 Oct 2014 14:24:21
Carmine.
Copyright: American Scientific Publishers
et al., 1988; Wu and McGinity, 2001).
Plasticizers are classified into three groups: Solvents/Vehicles
(i) Polyols type e.g., glycerol, propylene glycol, PEG The key function of a solvent system is to dissolve or
(Polyethylene glycol). disperse the polymers and other additives.
(ii) Organic esters e.g., phthalate esters, citrate esters, tri- The major classes of solvents being used are aqueous
acetin, dibutyl sebacete. (Water) and Nonaqueous (Alcohols, Ketones, Esters, Chlo-
(iii) Oils/glycerides e.g., castor oil, monoglycerides, rinated hydrocarbons). Because of environmental and eco-
acetylated, coconut oil, fractionated.
nomic concerns, water is the most commonly used solvent.

Anti-Adherents Miscellaneous Coating Solution Components


Anti-adherents are used as additives to avoid agglomera- Solid dosage form may be incorporated with several spe-
tion of the substrates during both the coating process and cial materials such as:
on subsequent storage. One of the most common anti- Flavours and sweeteners are added to mask unpleasant
adherents used in pharmaceutical coatings is talc, but since odours or to develop the taste. e.g., fruit spirits (organic
it has to be used at high concentration, it creates pro- solvent), aspartame, water soluble pineapple flavour.
cessing challenges, including clogging of the spray noz- Surfactants are ancillary to stabilize immiscible or insol-
zle during coating and particle sedimentation. It tends to uble ingredients in the coating. They facilitate substrate
decrease water vapour permeability and also the dissolu- wettability and promote coalescence of polymeric material
tion rate of drugs due to its hydrophobic nature. It also over the substrate’s surface e.g., Spans, Tweens etc.
affects the mechanical and adhesive properties of polymer Antioxidants are incorporated to stabilize a dye system
films so now Glyceryl monostearate has been found as an to oxidation and colour change e.g., oximes, phenols etc.
alternative to talc. Antimicrobials are added to inhibit microbial growth
in the coating composition. Various cellulosic materials
Opacifying Agents/Colorants are mainly prone to microbial growth and they can not
Pigments deliver elegance and stability enhancement to be stored in solution form e.g., Carbamates, alkylisothia-
the solid dosage form. Water-insoluble lakes and the iron zloinone, benzothiazoles etc.

64 J. Pharm. Sci. Pharmacol. 1, 57–67, 2014


Gaur et al. Film Coating Technology: Past, Present and Future

CURRENT TRENDS IN FILM COATING AND the same direction as the hot air resulting in an efficient
FUTURE DIRECTIONS process. Due to SCT’s unique air distribution plate design,
Opadry formulations provided numerous advantages ver- the tablets move very quickly and predictably through the
sus the use of individual raw materials including the spray zone, receiving only a small amount of coating per
reduction of the number of raw materials for Quality pass, and therefore achieving higher coating accuracy. The
control testing, reduced preparation time, reliable colour- process time is short, in seconds or in minutes as opposed
matched formulations, tremendous appearance and excel- to hours, and therefore gentler on the tablets (Systems,
lent mechanical parameters. However, opadry dispersion 2012).
solids must be stored as 10–15% w/w aqueous solution to Supercell™ Coating Technology may also be used for
attain workable 300–600 centipoises viscosity. coating of flat or highly oblong tablets or friable tablets.
Opadry II category consisting HPMC and polysaccha- In this process, drying is very fast, making it possible to
rides was introduced to increase productivity. The most coat extremely hygroscopic tablets. The deposition accu-
significant recent advances in the development of fully for- racy is sufficiently high to layer API onto tablets, and uni-
mulated aqueous film coatings have been the introduction form layers of taste masking or modified release coatings
of new film coatings based on polyvinyl alcohol (PVA) can be applied consecutively within a single continuous
and sodium carboxymethylcellulose (NaCMC). PVA-based batch.
films are known to have relatively low permeability for Unique features of super cell coating technology are:
moisture vapour and oxygen whereas NaCMC-based coat- (1) Continuous coating
ings are glossy and have low oxygen permeability and (2) Short processing time
relatively high permeability for water vapour. (3) Flexible modular design
Opadry aqueous moisture barrier (AMB) and Opadry II (4) No scale-up to parameters
85 series are two proprietary families of PVA-based prod- (5) Batch size for R&D (Minimum size ∼ 30 grams)
ucts that were commercialized in the mid to-late 1990s. (6) Enhancing technology
The Opadry AMB formulation were optimized to provide (7) Multi-layer coating
the lowest moisture vapour transmission rate. Opadry II (8) Low humidity process suitable for moisture sensitive
85 products give moisture vapour transmission rate almost materials.
as low as Opadry AMB but can be applied at
Delivered bysignificantly
Publishing Technology to: Guest User
higher spray rates. IP: 162.218.208.135 On: Tue, 14 Oct
Syloid ® 2014 14:24:21
FP Silicas in
Film coatings based on PVA and NaCMC Copyright:
offerAmerican
various Scientific Publishers
Pharmaceutical Film Coatings
advantages. Now, moisture-sensitive drugs can be coated Recently, film coatings have also shown encouraging
in an aqueous coating process by PVA-based coatings. results to enable the oral delivery of peptide therapeutics.
NaCMC based coatings provide demonstrable oxygen Syloid® FP silicas have been used as excipients in many
barrier properties and excellent aesthetic characteristics pharmaceutical formulations due to their unique morphol-
(Porter and Felton, 2010). ogy. The combined adsorption capacity, porosity, particle
size and greater surface area allow them to provide several
Supercell™ Coating Technology benefits simultaneously which can expedite manufacturing
The “standard” practice of tablet coating often delivers a and improve efficacy of the final dosage form. Syloid® FP
non-homogenous product. Because the tablets are loaded silica can be used in polymeric coating systems in combi-
in large rotating pans and vented for hot air drying, edges nation of vinyl/cellulose or acrylic polymers (13 Septem-
of tablets can get grounded off and intagliation can get ber 2010).
filled in by coating material leading to uneven coating on In standard concentrations—Addition of Syloid® 244FP
edges/corners and tablet faces. This inaccuracy limits the silica to film coating provides following advantages-
use of modified release coatings. In a laboratory, it is nec- Improved spray properties
essary to coat several kilograms of tablets at one time, Elimination of the need for talc
making R&D of a tablet dosage form costly and difficult. Improvement of suspension properties
Further extremely hygroscopic as well as flat or other Prevention of valve clogging
oddly shaped tablets cannot be coated using present tech- Minimal settling in spray lines
nology so SCT (Niro Pharma Systems) technology uses a Smoothen tablet surface
small, modular design that accurately deposits controlled Reduction of adhesion.
amounts of coating materials on friable and extremely Applications: Anti-tacking agent, Oral peptide delivery,
hygroscopic tablets. SCT’s continuous small-batch capable ODT formulations, Enteric coatings, Sustained release
coating process is predictable and efficient. In SCT, the coatings, Controlled release coatings (Grace Discovery).
tablets are coated in batches ranging from 30 to 120 grams, In recent years, there has been a growing focus on
which linearly scale up to production capacity. In this tech- conducting fundamental studies, through the application
nique, the tablets are covered with the polymer spray in of appropriate modelling techniques and novel analytical

J. Pharm. Sci. Pharmacol. 1, 57–67, 2014 65


Film Coating Technology: Past, Present and Future Gaur et al.

technologies. In addition, recent trends are directed toward in global austerity have pushed many pharmaceutical and
improvements in processing as well as development of biotechnology companies to seriously examine manufac-
novel release functionality. The following section provides turing costs. The lower cost associated with dry powder
a review to some of these areas. coating technology makes it attractive for both brand and
generic companies seeking to reduce operating expenses.
Another major driver in the future will be the needs of
PROCESS MODELLING SYSTEMS AND
advanced drug products specifically focused in the area of
THEIR APPLICATIONS
counterfeit resistance and amorphous formulation support.
Film coating process comprises various steps which can
Counterfeit drugs are a major problem facing global phar-
be direct or indirect. Direct parameters include air pres-
maceutical companies, with steps being taken to protect
sure and flow, temperature of coating spray and tablet the supply chain and also develop visually differentiated
core and spray rate. The indirect parameters take account products. Dry powder coating, particularly electrostatic dry
of droplet size distribution and viscosity, coating unifor- powder coating, can be used to prepare novel identification
mity and thickness. So, different modelling systems have marks onto drug products in a rapid cost effective manner
been proposed e.g., Digital video imaging, Discrete ele- leading to enhanced brand identification.
ment methodologies (DEM), Computational fluid dynam- Beyond this, the potential to eliminate the need for sol-
ics (CFD). vents allows for more effective application of coatings to
Discrete element method embodies different techniques moisture sensitive products. This opens up unique oppor-
implying on a large number of small particles to figure out tunities in the drug product design of amorphous systems
the movement and their interaction. In film coating pro- and may potentially play a role in future product designs.
cedure, DEM is used for estimating movement of tablets Given the potential of the technology, academic research
and predicting the coating uniformity. Computational fluid will continue in earnest as the pharmaceutical industry
dynamics applies the principles of fluid mechanics for film continues the adoption of the technology. Over time and
coating process (Felton and Porter, 2013; Felton, 2007). driven by a number of different factors, dry powder coating
The major application of process analytical technique is appears poised to become a major pharmaceutical coating
that it is amenable to automation. So it can be applied for technology in the future.
monitoring and controlling various unit operations. It can
Delivered
be applied for product moisture content, by Publishing
amount of coating Technology to: Guest User
IP: 162.218.208.135 On: Tue, Acknowledgment:
14 Oct 2014 14:24:21 The authors wish to express the
applied, endpoint of the process and properties
Copyright:ofAmerican
coating Scientific
gratitudePublishers
towards administrative authorities at ITS
e.g., porosity and density. Paramedical (Pharmacy) College, Muradnagar, Ghaziabad
However adaptation of PAT for coating process requires for providing necessary support during collection of data.
positioning of sensors in unsuitable conditions which
can have a bearing on sensor sensitivity. So various
sophisticated analytical processes e.g., terahertz refractive REFERENCES
Aulton, M. (ed.), (1995). Mechanical properties of film coats, Tay-
index (TRI) and pulse imaging (TPI), near-infrared and
lor&Francis, London.
raman spectroscopy (NIR), laser-induced breakdown spec-
Bodmeier, R. and Paeratakul, O. (1994). Mechanical properties of dry and
troscopy (LIBS) and confocal laser techniques can be
wet cellulosic and acrylic films prepared from aqueous colloidal polymer
applied offline. All of these techniques can also be used dispersions used in the coating of solid dosage forms. Pharmaceutical
online since these are non-destructive except LIBS. Research 11, 882–88.
NIR methods can be employed for determining the coat- Chen, W, Chang, S.-Y., Kiang, S., Early, W., Paruchuri, S., and Desai,
ing amount to predict drug release rate in combination D. (2008). The measurement of spray quality for pan coating process.
with multivariate analysis. NIR spectroscopy can be used J. Pharm. Innov. 3, 3–14.
to estimate an API in a coated tablet with ± 4% target Chen, W., Chang, S. Y., Kiang, S., Marchut, A., Lynberg, O., Wang, J.,
value in comparison to HPLC. Major advantage of NIR Rao, V., Desai, D., Stamato, H., and Early, W. (2010). Modeling of pan
spectroscopy is its non-invasiveness and rapidity. However coating process: Prediction of tablet content uniformity and determination
of critical process parameters. J. Pharm. Sci. 99, 3213–24.
it cannot be used with drugs in hydrate form. Raman spec-
troscopy is less sensitive to hydrates. TPI technique can be Cole, G. (1998). Pharmaceutical Coating Technology, Taylor and Francis,
London.
used to determine the amount of coating in a side-vented
pan (Felton, 2007; Felton and Porter, 2013). Dillon, R. E., Matheson, L. A. and Bradford, E. B. (1951). Sintering of
synthetic latex particles. Journal of Colloid Science 6, 108–17.
Felton, L. A. (2007). Characterization of coating systems. AAPS Pharm.
CONCLUSION Sci. Tech. 8, 112.
Based on the facts regarding film coating process, we can Felton, L. A. and Porter, S. C. (2013). An update on pharmaceutical film
emphasize that various recent trends may drive the indus- coating for drug delivery. Expert Opinion on Drug Delivery 10, 421–35.
try closer to large scale adoption of dry powder coating Franz, R. and Doonan, G. (1983). Measuring the surface temperature of
technologies for oral delivery. First, the current changes tablet beds using infrared thermometry. Pharm. Technol. 7, 55–67.

66 J. Pharm. Sci. Pharmacol. 1, 57–67, 2014


Gaur et al. Film Coating Technology: Past, Present and Future

Harris, M. R. and Sellassie, G. (eds.), (1997). Aqueous Polymeric Coat- within film coats part II: Temperature and relative humidity variation
ing for Modified Release Oral Dosage forms, Marcel Dekker Inc., Ney within a tablet bed during aqueous film coating in an accela-cota. Drug
York. Development and Industrial Pharmacy 17, 1191–99.
Hogan, J. (1998). Pharmaceutical Coating Technology, Taylor and Francis Opadry® Complete Film Coating System. Coating Parameters–
Ltd., London. Aqueous Formulas, Colorcon, Inc., North America, BPSI Holdings,
Lachman, L., Lieberman, H. A., and Joseph, L. K. (1989). The Theory LLC.
and Practice of Industrial Pharmacy vol. 3 Varghese Publishing House, Porter, C. (1990). Coating of Pharmaceutical Solid Dosage Forms, Mack
Mumbai. Publishing Company, Easton, Pennsylvania.
Lehmann, K. (ed.), (1994). Coating of multiparticulates using polymeric Porter, S. C. (ed.), (2011). Scale-Up of Film Coating, Informa Healthcare,
solutions: Formulation and process considerations, Marcel Dekker, Inc., New York.
New York.
Porter, S. C. and Felton, L. A. (2010). Techniques to assess film coat-
Libermen, H. and Lachman, L. (2003). Pharmaceutical Dosage Forms: ings and evaluate film-coated products. Drug Development and Industrial
Tablets, Marcel Dekker Inc., N.Y, Vols. 1–3. Pharmacy 36, 128–42.
Lipper, R. D., Desai, D., and Kiang, S. (September 11–12, 2006). Case Rekhi, G. S., Porter, S. C., and Jambhekar, S. S. (1995). Factors affecting
Study: Implementation of Design Space Concepts in Development of an the release of propranolol hydrochloride from beads coated with aque-
Active-Coated Tablet In: Real World Applications of PAT and QbD in ous polymeric dispresions. Drug Development and Industrial Pharmacy
Drug Process Development and Approval, Bristol-Myers Squibb Pharma- 21, 709–29.
ceutical Research Institute, Arlington, Virginia, USA.
Sadeghi, F., Ford, J. L., Rubinstein, M., and Rajabi-Siahboomi, A. R.
Lippold, B. C. and Monells, P. P. (2001). Film formation, reproducibility (2001). Study of drug release from pellets coated with surelease con-
of production and curing with respect to release stability of functional taining hydroxypropyl methylcellulose. Drug Development and Industrial
coatings from aqueous polymer dispersions. Pharmazie 56, 5–17. Pharmacy 27, 419–30.
Malm, C. J. and Waring C. E. (1937). Cellulose esters containing dicar- Savage, G. V. and Rhodes, C. T. (1995). The sustained release coating of
boxylic acid groups and process of making the same. solid dosage forms: A historical review. Drug Development and Indus-
Mazer, T. B., Meyer, G. A., Hwang, S. M., Candler, E. L., Drayer, L. trial Pharmacy 21, 93–118.
R., and Daab-Krzykowski, A. (1992). System for delivering an active Seitz, J. A., Swarbrick, J., and Boylan, J. C. (1988). Aqueous film coat-
substance for sustained release. ing, Encyclopedia of Pharmaceutical Technology, Marcel Dekker, New
Narang, A. K. M., Castoro, J., Varia, S., and Desai, D. (2011). Effect of York, pp. 337–49.
Pro- and Anti-Oxidants on the Formation of Formyl Species in PVA- and Singh, P., Solanky, T. K., Mudryya, R., Pfefferc, R. and Davea, R. (2001).
PEG-Based Tablet Coating Material, AAPS, Washington,
Delivered by D. C., USA.
Publishing Technology
Estimation ofto: Guest
coating timeUser
in the magnetically assisted impaction coating
Narang, A. S., Desai, D., and Badawy,IP: 162.218.208.135
S. (2012). On: Tue,
Impact of excipient 14 Oct
process. 2014
Powder 14:24:21
Technology 121, 159–67.
Copyright:
interactions on solid dosage form stability. Pharm. American Scientific
Res. 29, 2660–83. ® Publishers
Syloid FP silica excipients—more than just Silica. (Belgium Fred Mon-
Ogaji, I. and Nnoli, O. (2010). Film coating potential of okra gum using suur, Grace Davison Discovery Sciences) (13 September 2010).
paracetamol tablets as a model drug. Asian J. Pharm. 4, 130–34. Systems GNP. (2012). SUPERCELL™ Tablet Coating Technology (SCT).
Ogaji, I. J. and Hoag, S. W. (2011). Effect of grewia gum as a suspend- Niro Inc. 9165 Rumsey Road Columbia, MD 21045 USA.
ing agent on ibuprofen pediatric formulation. AAPS PharmSciTech. 12, Wu, C. and McGinity, J. W. (2001). Influence of Ibuprofen as a solid-
507–13. state plasticizer in Eudragit RS 30D on the physicochemical properties
Ogaji, I. J., Okafor, I. S., and Hoag, S. W. (2013). Grewia gum as a poten- of coated beads. AAPS PharmSciTech. 2, 1–9.
tial aqueous film coating agent. I: Some physicochemical characteristics Zheng, W. and McGinity, J. W. (2003). Influence of Eudragit NE 30 D
of fractions of grewia gum. J. Pharm. Bioall Sci. 5, 53–60. blended with Eudragit L 30 D-55 on the release of phenylpropanolamine
Okutgen, E., Jordan, M., Hogan, J. E., and Aulton, M. E., (1991). Effects hydrochloride from coated pellets. Drug Development and Industrial
of tablet core dimensional instability on the generation of internal stresses Pharmacy 29, 357–66.

J. Pharm. Sci. Pharmacol. 1, 57–67, 2014 67

View publication stats