Coating of pharmaceutical dosage forms

Coating
of Pharmaceutical solid
dosage forms

• Benefits of the process of coating of
pharmaceutical dosage forms:
1. Improved esthetic qualities of the product.
2. Masking of unpleasant taste and odor.
3. Enabling the product to be more easily swallowed by
the patient.
4. Facilitating handling, particularly in high-speed filling
& packaging lines.
5. Improving product stability.
6. Modifying drug-release characteristics.

Types of Coating
Coatings
Sugar coatings Film coatings
Conventional film
coatings
Functional film
coatings
Delayed-Release
Film coatings
Extended-Release
Film coatings

A. Film Coating
I. Introduction to film coating.
II. Ingredients used in film coating.
III. Preparation procedures of film coating liquid.
IV. Conventional film coating.
V. Modified-Release film coatings
VI. Technical procedures in film coating process
VII. Problems in film coating.

I. Introduction
• The process of film coating is that one involving the application of
thin (in the range of 20- 200 um) , polymer-based coatings to an
appropriate substrate (tablets, beads, granules, capsules, drug
powders, and crystals).
• The process should guarantee the following criteria:
1. Balance between, and control of, the coating liquid addition
rate and drying process.
2. Uniformity of distribution of the coating liquid across the
surface of product being coated.
3. Optimization of the quality (both visual and functional) of the
final coated product.

• Despite that the elegance of sugar-coated tablets is thought to be
superior, Film-coating process has replaced sugar-coating due to the
following advantages:
1. Substantial reduction in quantity of coating applied (2 - 4% for film coating,
compared with 50 -100% for sugar coating)
2. Faster processing times.
3. Improvement in process efficiency and output.
4. Greater flexibility in optimizing formulations as a result of the availability of
a wide range of coating materials and systems
5. A simplified process (compared to sugar coating) that facilitates
automation
6. Ability to be applied to a wide range of pharmaceutical products “e.g.,
tablets, capsules, granules, non-pareils, powders, drug crystals”.

II. Ingredients used in film coating
• A typical formulation of film coating contains:
1. Polymer.
2. Plasticizer.
3. Colorant.
4. Solvent (vehicle).
• Certain features of film coating formulation, discussed at
the following table, are important and much affected by the
ingredients used in the formulation.

Important features of film coating
Feature Has impact on
1. Mechanical properties
(Tensile strength & Elasticity modulus)
•Visual quality of coating.
•Resistance to damage on handling.
•Barrier properties of coating.
•Drug-release characteristics from MR products.
•Taste-masking efficiency.
2. Permeability characteristics •Barrier properties of coating.
•Product stability.
•Drug-release characteristics from MR products.
•Taste-masking efficiency.
3. Coating solution viscosity •Spraying characteristics.
•Interaction with the substrate.
•Visual quality of coating.
4. Hiding power •Visual quality.
•Quantity of coating needed for uniform appearance.
•Stability of photo-labile APIs.

1. Polymers
• the polymer is the major ingredient, Consequently, this material will
have the greatest impact on the final properties of the coating.
• Polymers are a multiplicity of differing chemical types, each in turn
often having various grades (as determined by viscosity or molecular
weight).
• Due to the batch-to-batch variations resulting from the polydisperse
nature for a particular grade of polymers, it’s necessary to define the
material in terms of:
1. Chemical structure.
2. Molecular weight
3. Molecular weight distribution.
• This can be determined using gel permeation (or size exclusion)
chromatography, whereby average molecular weight, molecular weight
distribution & polydispersity can be determined.
• Viscosity as a sole test, will not give a full image for the polydisperse
nature of the polymer.

Effect of polymer M.Wt on coating properties
Property Effect of increasing polymer M.Wt
1. Tensile strength •Increases
2. Elastic modulus •Increases “i.e., coating becomes less elastic”
3. Film adhesion •Decreases
4. Solution viscosity •Significantly increases
5. Film permeability •Typically unaffected, unless the structural “mechanical”
properties improves with the increase in the polymer M.Wt

2. Plasticizers
• Plasticizers reduce the glass-transition temperature of amorphous polymers
and impart flexibility.
• below the Tg there is a critical cessation of molecular motion on the local
scale, Under these temperature conditions, the polymer exhibits many of the
properties of inorganic glasses, including toughness, hardness, stiffness, and
brittleness.
• So the Tg is described as one below which a polymer is brittle, and above
which it is flexible (temperature above which there is an increase in the
temperature coefficient of expansion).
• The basic requirements to be met by a plasticizer are:
1. Permanence (Plasticizer should have a low vapor pressure & low diffusion rate within
the polymeric film)…. Available in high M.Wt plasticizers.
2. Compatibility (the plasticizer should be miscible with the polymer and exhibit similar
intermolecular forces to those present within the polymer).

• Sometimes there are systems needs two types of plasticization, The
first is
• Internal plasticization, and refers to the situation in which chemical changes
are made within the structure of the polymer itself ”Substitution and Change
in polymer chain length”, as with copolymers (exemplified by many of the
acrylic polymers systems used in film coating).
The second, termed
• External plasticization, occurs when an external additive (the plasticizer) is
combined in admixture with the polymer.
• Effective plasticization is critical when using aqueous polymeric
dispersions to ensure that sufficient free volume exists at normal
processing temperatures to facilitate coalescence of the polymeric
particles into a continuous film.
• the magnitude of the effect on the coating film properties is very much
dependent on the compatibility, or degree of interaction, of the
plasticizer with the polymer, much more than the quantity of the
plasticizer in the coating formula.
• So, plasticizers. by their very nature. are not universal, since selection
is very much determined by which polymer is being used.

Effect of plasticizers on the properties of film coating
Property Effect of increasing plasticizer concentration
1. Tensile strength •Decreased
2. Elastic modulus •Decreases “i.e., coating becomes more elastic”
3. Film adhesion •May be increased, but results are variable
4. Solution viscosity • Increased. and magnitude of effect dependent
on molecular weight of plasticizer
5. Film permeability •Can be increased or decreased, depending
on chemical nature of plasticizer
6. Glass-transition
temperature
•Decreased. but magnitude of effect dependent
on compatibility with polymer

3. Colorants
• Colorants are included in many film-coating formulations to improve
the appearance and visual identification of the coated product, with
certain types have other physical functions.
• Colorants used in film-coating:
1. Water-soluble dyes (eg. FD&C Yellow #5 and FD&C Blue #2)
2. Aluminum lakes (of FD&C water-soluble dyes)
3. Inorganic pigments (eg. titanium dioxide, iron oxides. calcium sulfate,
calcium carbonate)
4. "Natural" colorants (eg. riboflavin, turmeric oleoresin. carmine 40).
• Using pigments is preferable to the use of water-soluble colorants due
to the following:
1. Ability to increase solids content of coating solution without dramatically
affecting viscosity. (particularly advantageous in aqueous film coating)
2. Ability to improve the moisture barrier properties of film coatings.

• Inadequate pigment dispersion leads to coating defects:
1. Inhomogeneous Color distribution over the film.
2. Surface roughness of the coating.
• Requirements of coloring in film coating:
1. Create a given visual effect.
2. Ensure that the appearance is as uniform as possible throughout the
particular batch of coated product.
3. Coloring is consistent from batch-to-batch.
• Contrast ratio is a useful parameter in determining which type of colorant to be
used and regarded as a measure of the hiding power of the coloring used:
• Contrast ratio = Yb / Yw * 100
• Yb: Tristimulus value of a certain film over a black background.
• Yw: Tristimulus value of the same film over a white background.
• Colored films having contrast ratios close to 100 exhibit excellent hiding power,
whereas those having values close to zero are almost transparent (and thus
have poor hiding power).

• Choosing a colorants with high contrast ratios greatly serves in film coating properties
enhancement by:
1. Effectively mask the appearance of the substrate without requiring the use of
excessive quantities of colorant (which could increase the risk of physical defects
in the coated product).
2. Avoidance of applying excessive quantities of coating (which impacts total cost
of the process).
• Practically, it’s been found that the best coloring are:
• certain inorganic pigments (eg. titanium dioxide and iron oxides) due to the close
values of refractive indices between them and the polymer.
• those that absorb the higher wavelengths of visible light (e. g., FD&C Blue #2).

Effects of pigments on the properties of film coating
Property Effect of increasing pigment concentration
1. Tensile strength •Decreased (effect may be minimized by effective pigment
dispersion).
2. Elastic modulus •Increases “i.e. elasticity decreases”
3. Film adhesion •Little effect.
4. Solution viscosity •Increased, but not substantially.
5. Film permeability •Decreased, unless critical pigment volume concentration
is exceeded. “corrupt the polymer network”
6. Hiding power •Increased, but magnitude of effect dependent on
refractive index of pigment, and light absorbed by pigment

4. Solvents
• the rise in importance of aqueous
film coating has virtually
eliminated solvent selection from
the formulation process.
• However, certain types of film
coatings and film-coating
processes require that some
organic solvents still be used.
Thus, to a limited extent, selection
of an appropriate solvent may still
be necessary.
Common solvents used in film
coating
Class Example
1. Water ---------
2. Alcohols •Ethanol
•Methanol
•Isopropyl alcohol
3. Esters •Ethyl acetate
•Ethyl lactate
4. Ketones •Acetone
5. Chlorinated
hydrocarbons
•Methylene chloride
•1,1,1, trichlorothane

• Factors governing the selection of the
appropriate solvent:
1. the ability to form a solution with the polymer of choice “optimal
polymer solution will yield the maximum polymer chain extension,
producing films having the greatest cohesive strength and thus the
best mechanical properties”.
2. a controllable deposition rate of the polymer onto the surface of the
substrate, the volatility of the solvent system is an important
factor.
• NB: In the case of solvent system, the solubility of the
polymer in the least volatile solvent component must be
guaranteed, otherwise the solvent-polymer thermodynamic
balance changes as evaporation progresses, leading to
polymer precipitation before a cohesive film being formed.

III. Conventional film coating
• The selection of coating formula ingredients is based on factors that affect:
• the mechanical properties (such as tensile strength, elasticity, and
adhesion) of the coating, allowing the smoothest, glossiest coatings to be
obtained, and produce coatings that readily dissolve in the human GIT.
Polymers:
• The most popular class of polymers used in conventional film coating are:
1. Cellulosics, many of which have good organic-solvent and aqueous
solubility, thus facilitating the transition to aqueous film coating.
2. Polyvinyl pyrrolidone, “films are brittle and hygroscopic.”
3. Polyethylene glycol, “films are waxy, hygroscopic, and soften readily at
only moderately elevated temperatures.”
4. Acrylates:
1. Dimethylaminoethyl methacrylate methacrylic acid ester copolymer
“Eudragit E”….“soluble in water at only low pH, making it particularly
attractive for taste masking, only organic-based”.
2. Ethyl acrylate-methyl methacrylate copolymers, also water insoluble,
but available as aqueous latex-coating systems.

Polymers Used in Conventional Film-Coating formulations
Class Example
1. Cellulosics •Hydroxypropyl methylcellulose “HPMC”.
•Hydroxypropyl cellulose “HPC”.
•Hydroxyethyl cellulose “HEC”.
•Methylhydroxyethylcellulose “MHEC”.
•Methylcellulose
•Ethylcellulose
•Sodium carboxymethylcellulose “CMC sodium”
2. Vinyls •Polyvinyl pyrrolidone.
3. Glycols •Polyethylene glycols
6. Acrylates •Dimethylaminoethyl methacrylate methylacrylic acid ester copolymer
“Eudragit E”
•Ethylacrylate-methylmethacrylate copolymer

• Hints:
• HPMC films have superior tensile properties.
• HPC films tend to be more elastic (i.e., exhibit lower elastic moduli), and
possess better adhesive properties.
• Since each of these polymers is available in several grades, the common
practice is to use the lower molecular weight grades of each in aqueous
film coating in order to optimize the properties of coating solutions with
respect to solids content and solution viscosity.

• Plasticizers:
– With aqueous film-coating formulations, the general preference is to
use water-soluble plasticizers, since this approach helps to facilitate
interaction between the polymer and plasticizer. For this reason,
plasticizers such as glycerol, propylene glycol, the polyethylene
glycols and triacetin are often used with aqueous formulations.
– Specifically for HPMCs, the PEGs are the most effective plasticizers
for this cellulosic polymer, with effectiveness being inversely
proportional to the molecular weight of the polyethylene glycol
chosen.
– Being hygroscopic, that facilitates plasticization process by helping
retaining the amount of moisture in the polymeric film.
– NB: Use of triacetin as a plasticizer in aqueous formulations, although
less popular, may have certain advantages when trying to improve the
moisture barrier properties of the film coating.

Common Plasticizers Used in conventional film coating
Class Example
1. Polyhydric alcohols •Propylene glycol
•Glycerol
•Polyethylene glycols
2. Acetate esters •Glyceryl triacetate (Triacetin)
•Triethyl citrate
•Acetyl triethyl citrate
3. Phthalate esters • Diethyl phthalate
• Dibutyl phthalate
6. Glycerides •Acetylated monoglycerides “eg. Glyceryl
monostearate”.
7. Oils •Castor oil
•Mineral oil

IV. Modified-Release film coating
• The United States Pharmacopeia/National Formulary (USP/NF) has simplified
this terminology somewhat by defining a modified-release dosage form as:
• “one in which the drug-release characteristics of time course and/or
location are chosen to accomplish therapeutic or convenience objectives
not offered by conventional dosage forms….”.
• Under this umbrella definition, the USP/NF recognizes two types of modified-
release dosage form:
1. Extended release: One that permits at least a twofold reduction in dosing
frequency as compared to the situation in which the drug is presented as a
conventional dosage form (also called sustained-release or controlled-
release dosage forms).
2. Delayed release: One that releases the API at some time other than
promptly after administration (e.g.. enteric-coated products).

a. Enteric Film Coatings
• Enteric coatings are those which remain intact in the stomach (and
exhibit low permeability to gastric fluids). but break down readily once
the dosage form reaches the small intestine.
• The purposes of use of such drug delivery system are:
1. To protect & maintain the activity of drugs that are unstable
when exposed to the gastric milieu (e. g., erythromycin and
pancreatin).
2. To minimize either nausea or bleeding that occurs with those
drugs that irritate the gastric mucosa (e.g. aspirin and certain
steroids).
• Modern enteric coatings are usually formulated with synthetic polymers
that contain ionizable functional groups that render the polymer water
soluble at a specific pH value. Such polymers are often referred to as
polyacids.
• Since many of these polymers are esters, they may be subject to
degradation (as a result of hydrolysis) when exposed to conditions of
elevated temperature and humidity. Such hydrolysis can result in a
substantial change in enteric properties.

Examples of Enteric-Coating Polymers
Polymer Comments
• Cellulose acetate phthalate (CAP) •Subject to hydrolysis “high”.
• Cellulose acetate trimellitate (CAT) •Subject to hydrolysis
• Polyvinyl acetate phthalate (PVAP) •Subject to hydrolysis “low”.
• Hydroxypropyl methylcellulose phthalate (HP) •Subject to hydrolysis “medium”
• Hydroxypropyl methylcellulose acetate succinate
(HPMCAS)
•Subject to hydrolysis “low”
•Poly methacrylic acid – ethylacrylate copolymer 1:1
“Eudragit L100-55”
•Poly methacrylic acid – methylmethacrylate copolymer 1:1
“Eudragit L100”
•Relatively high dissolution pH
•Poly methacrylic acid – methylmethacrylate copolymer 1:2
“Eudragit S100”
•Relatively high dissolution pH

• the special aqueous solubility requirements for an enteric polymer have delayed the
routine employment of aqueous enteric-coating technology.
• More recently, various systems of aqueous enteric coating have been introduced.
• many of the coating systems exist as dry powders, with the coating liquid being
prepared shortly before use by dispersing (or dissolving) the polymer in water.
• The reason for supplying many enteric coating systems as dry powders is to avoid
problems of poor stability (due to hydrolysis) when these polymers are exposed
to water for extended periods.
• Important factors that can influence the behavior of enteric coatings:
1. The nature of the drug in the dosage form (the presence of aspirin, for example, can
greatly influence dissolution of the coating).
2. The quantity of coating applied (application of excessive quantities of coating can
substantially delay release of drug from the dosage form).
3. The presence of imperfections in the coating (fissures or "pick" marks will destroy the
integrity of the coating).
4. The dissolution pH of the polymer used in the coating.
5. The effect of in vitro test conditions (dissolution of the coating, and ultimate drug release,
can be affected dramatically by the pH and ionic strength of the test solutions and the
agitation rate).

Examples of Aqueous Enteric-Coating Systems
Product Form Polymer Comments
Eudragit L 30 D Latex dispersion Poly (MA-EA) 1:1 •System essentially contains only the polymer
Eudragit L100-55 Spray-dried
latex
Poly (MA-EA) 1:1 •Requires dispersing in water with addition of
alkali
•System only contains polymer
HP-F Dry powder HP •Requires dispersing in water
•System only contains polymer
Coateric Dry powder PVAP •Complete system.
•Requires dispersing in water with addition of
ammonia.
Aquateric Spray-dried
pseudolatex
CAP •System essentially contains only polymer
•Requires dispersing in water
HPMCAS Dry powder HPMCAS •System contains only polymer
•Requires dispersing in water
CAP Dry powder CAP •System contains only polymer
•Requires dissolving in water with aid of alkali
(ammonia)
CAT Dry powder CAT •System contains only polymer
•Requires dissolving in water with aid of alkali
(ammonia)

b. Sustained-Release, or Controlled-Release film coatings
• Drug release from such sustained-release products is moderated by the
film coating Which acts as a membrane that allows infusion of GI fluids
and the outward diffusion of dissolved drug.
• In some instances, the release process may be augmented by a coating
that slowly dissolves (e.g. shellac), or is subject to digestion by enzymes
(e.g., fats and waxes).
• NB: natural substances when used do not give predictable drug release
profile, unlike the synthetic ones…

Examples of coating materials used in Sustained-
Release film-Coating formulations
Coating material Membrane characteristics
• Fats and waxes (e. g., beeswax,
carnauba wax, cetyl alcohol,
cetylstearyl alcohol)
•Permeable and erodible
• Shellac •Permeable and soluble (at high pH)
• Zein •Permeable and soluble (at high pH)
• Ethylcellulose •Permeable
• Cellulose esters (e. g., acetate) •Semipermeable
• Silicone elastomers •Permeable (when PEG added)
• Acrylic esters • Permeable

• As with other types of film coating. great interest has been shown in using
aqueous-coating technology for sustained-release products.
• These coating systems typically consist of aqueous dispersions of water-insoluble
polymers which form films by a process of coalescence of submicron
polymer particles.
• This process can be greatly affected by conditions used in the coating process.
and variable results (as they relate to ultimate drug-release characteristics)
can often be attributed more to lack of control over the coating process (or
choice of inappropriate processing parameters) rather than to any variability
in the aqueous dispersion used.

Examples of Aqueous polymeric dispersions for sustained-
release
film coating
Material Polymer Comments
Surelease Ethylcellulose •Aqueous polymeric dispersion contains requisite
plasticizers
•Addition of lake colorants should be avoided
because of alkalinity of dispersion
Aquacoat Ethylcellulose •Pseudolatex dispersion
•Requires addition of plasticizers to facilitate film
coalescence
Eudragit NE 30 D Poly(ethylacrylate-methyl
methacrylate) 2: 1
•Latex dispersion
•No plasticizers required unless improved film
flexibility is desired
Eudragit RL 30 D Poly(ethylacrylate-methyl
methacrylate)triethyl
ammonioethyl methacrylate
chloride 1: 2: 0.2
•Aqueous polymeric dispersion
Eudragit RS 30 D Poly(ethylacrylate-methyl
methaeryIate)triethyl
ammonioethyl methacrylate
chloride 1: 2: 0. 1
•Aqueous polymeric dispersion

• Drug release from sustained-release systems can be described by application of Fick's
first law of diffusion.
• The rate of drug release through the membrane is directly proportional to
1. surface area,
2. diffusion coefficient,
3. drug solubility in and drug concentration gradient across the membrane,
and inversely proportional to membrane thickness.
• With respect to drug-release characteristics, variable results may occur through inability
to control many of influencing factors. For example:
1. Variations (from batch-to-batch) in size and shape of the core
material (to be coated) would certainly cause variations in
surface area and coating thickness.
2. Variations in coating structure may well result from variable
processing conditions that cause picking or spray drying
(particularly with organic-solvent-based coating solutions) and
incomplete coalescence with aqueous polymeric dispersions.
3. general variation in process efficiencies (which influence
uniformity of distribution. and overall quantity applied, of the
coating material)

Factors influencing drug release from a sustained-release
film-coated dosage form
Parameter Influenced by
1. Surface area •Size, size distribution, and surface topography of
material being coated.
2. Diffusion coefficient •Formulation of film coating
•Structure of coating
•Nature of drug
3. Drug-concentration gradient across
Membrane
•Initial drug loading
•Drug content inside the membrane at any
intermediate time
•Agitation rate (which influences drug
concentration on outside of membrane)
4. Membrane thickness •Size, size distribution, and surface topography of
material being coated
•Quantity of coating material applied (related to
theoretical quantity of coating to be applied, and
coating efficiency)

III. Preparation procedures of film
coating liquid
• Coating liquids, from the formulation aspect, are divided
into two types:
1. Pseudo-dispersions “ the polymer dissolves in the solvent, and the
dispersed phase results from the insoluble detackifier &/or the insoluble
lakes or pigments”…e.g. HPMC-based coating liquid
2. True dispersions “the polymer is dispersed, not soluble in the solvent,
beside the other dispersed ingredients”……e.g. PVAP-based coating
liquid.

1. Important measures in pseudo-dispersions preparation
• Generally, coating liquid is prepared using a high-shear mixer
equipped with a homogenizing part.
• In case of soluble cellulosics “e.g. HPMC, HPC, CMC sodium” the
solubility is slow due to the sudden gelling when adding to water, so
it’s either:
1. to let overnight standing “ soaking”, where the formed gel
dissolves slowly in water.
2. Disperse it in part of hot water “NLT 80 degree Celsius”,
then adding the rest water cold.

• If the plasticizer &/or the colorant are water soluble exist, it
must be added directly to the polymer solution.
• If a detackifier &/or a pigment or a lake exist, it must be
homogenized externally, then added to the polymer solution
with continuous stirring.
• Allover the coating process, stirring should continue so that
air entrapment in the liquid is avoided, or minimized at least.

2. Important measures in true dispersions preparation
• Generally, stirring must be efficient and last for a long
period to maintain the homogenous dispersity of coating
ingredients esp. the polymer in the solvent.
• The polymer should be the last ingredient in addition, care
must be taken upon stirring to avoid air entrapment.
• In case of enteric polymers, most of them needs the
addition of an alkali to facilitate homogenous dispersion
and avoid coagulation of the polymer particles, e.g.
Eudragit L100-55.
• Polymers with high deviation in surface tension value from
water, should be admixed with a surfactant to facilitate
1. the dispersion of the polymer.
2. wetting of the substrate by the coating dispersion.
3. coalescence of the polymeric film upon drying.

3. Important measures in pseudolatices preparation
• E.g. Eudragit E30 D, Aquacoat 30% ECD.
• Stirring is the most important measure to be taken in
consideration, where air entrapment is the most
hazardous factor.
• If an external plasticizer &/or detackifier is needed, addition
must be done very carefully while stirring to avoid any
disturbances in the pseudolatex structure.

IV. Technical procedures in film
coating process
1. Mechanism of film coating process
2. Coating process in general
3. Process parameters to consider

1. Mechanism of film coating process
• Film coating liquids are applied almost always utilizing
spray-atomization technique.
• In the spray-application process, bulk coating liquids are
finely atomized and delivered in such a state that
droplets “of coating liquid” retain sufficient fluidity to wet
the surface of the product being coated, spread out, and
coalesce to form a film.
• Because of the highly adhesive (or "tacky") nature of
partially dried droplets, it is imperative that the droplets
of coating liquid dry almost instantaneously the moment
they contact the surface of the substrate; otherwise
sticking and picking will occur.

• Uniformity of distribution of coating liquid is controlled by:
1. Uniformity of application of the coating liquid i.e., number of spray
guns used, types of spray patterns used & fineness of atomization of
coating liquid.
2. Uniformity of mixing (controlled by pan speed, baffle design, tablet
size & shape) of the product being coated.
• Unlike sugar coating, it is not desirable in film coating to
have partially dry coating material being transferred from
one tablet to another, since this would create imperfections
in the coating that would be readily evident at the end of the
coating process.
• The tumbling action, however, has an effect on the ultimate
coating structure promoting sufficient flow of the coating
inducing a leveling effect.

•Factors affecting the quality of film coating
• To better understand those factors affecting the quality “both visual &
functional” of the finished coated product, it’s necessary to examine
the factors affecting:
1. Interaction between the core material (substrate) and the applied coating.
2. The drying process.
3. The uniformity of distribution of the coating.

Factors influencing interaction between substrate & coating
Factor Has influence on
1. Tablet core
Ingredient
Porosity
Surface roughness
•Wetting by coating liquid.
•Adhesion of dry film.
•Adhesion of dry film.
•Wetting by coating liquid.
•Spreading of coating liquid across surface.
•Roughness of coating.
2. Coating liquid
Solids content
Viscosity
Surface tension
•Roughness of dry coating.
•Coating liquid viscosity.
•Spreading of coating liquid across surface of substrate.
•Coalescence of droplets of coating liquid into a continuous film.
•Wetting of surface of substrate by coating liquid.
•Spreading of coating liquid across surface of substrate.
•Coalescence of droplets of coating liquid into a continuous film.
3. Drying process
Drying rate
Heat
•Viscosity of coating liquid at time of contact with surface of substrate
•Structure of dried coating.
•Development of internal stress within film (and effect of adhesion & cohesion).
•Mechanical properties of coating (and effect on defects).

Factors influencing the drying process
1. Spray equipment
Nozzle design
Atomization air
Number of used spray guns
•Fineness of atomization of coating liquid (and thus evaporation rate of solvent/vehicle)
•Fineness of atomization of coating liquid (and thus evaporation rate of solvent/vehicle)
•Uniform distribution of coating liquid.
•Avoidance of localized overwetting.
2. Drying Conditions
Air flow, temp, humidity •Rate at which solvent/vehicle can be removed from the coating liquid.
•Product temperature.
3. Spray rate
Nozzle design, no of spray
guns, pumping system
•Rate at which solvent/vehicle can be removed from the coating liquid.
•Product temperature.
4. Solids content of coating
liquid
•Quantity of solvent/vehicle that must be removed from coating liquid.

Factors influencing uniformity of distribution of coating
1. Spray equipment
Nozzle design
Atomizing air
Number of spray guns
•Fineness of atomization of coating liquid.
•Area over which coating liquid is applied
•Fineness of atomization of coating liquid.
•Area over which coating liquid is applied.
•Length of coating process.
2. Drying conditions
Air flow, temp, humidity •Efficiency of the coating process (i.e., amount of coating that ends up on core material).
3. Spray rate
Drying rate •Length of coating process.
•Amount of coating liquid that is deposited on substrate at each pass through spray zone.
•Amount of coating that is lost during coating.
4. Solids content of coating
liquid
•Length of coating process.
•Smoothness of the dried coating.
5. Pan speed •Uniformity of mixing.
•Loss of coating due to attritional effects.
6. Baffles of coating pan •Uniformity of mixing.

FORMULATION OF FILMS FROM POLYMERIC SOLUTIONS
• The film forming process & internal structure of the final dried coating
depends mainly on:
• Rate of solvent evaporation.
• Rate of solvent evaporation, in turn, is controlled by:
• The solvent latent heat of vaporization.
• The drying conditions provided in the process.
• Film formation generally comprises:
1. Initial rapid evaporation of solvent from the atomized droplets of coating liquid,
causing an increase in polymer concentration (and, hence, viscosity) and
contraction in volume of the droplets.
2. Further loss of solvent from the film (that is, coalescing on the surface of the
dosage form) at a slower rate which is now controlled by the rate of diffusion of
solvent through the polymer matrix.
3. Immobilization of the polymer molecules at the “solidification point”.
4. Further gradual solvent loss from the film at a very much reduced rate.

• Solvent loss from the film coating will be continuous but at an ever decreasing
rate.
• Solvent loss from the polymer matrix is governed by the amount of space between
the polymer molecules (usually termed the free volume).
• As solvent loss progresses. the Tg of the polymer film increases and free volume
decreases. Ultimately, free volume becomes so small that further solvent loss is
so restricted that total removal of solvent from the coating becomes almost
impossible.
• Total solvent removal requires heating the film to a temperature significantly
above the Tg of the solvent-free polymer “the purpose of plasticizer”.
• Solvent loss (from the coating) that occurs beyond the solidification point creates
shrinkage stresses that contribute to the internal stress within the coating, leading
to mechanical defects.

FORMULATION OF FILMS FROM AQUEOUS
POLYMERIC DISPERSIONS
• Film formation from aqueous polymeric dispersions requires the
coalescence of polymer particles into a continuous film.
• Drying of such a system (i.e., the removal of water) is often quite rapid,
whereas coalescence can be a much slower process, extending into
weeks and months if appropriate formulation and processing
parameters are not used.
• The actual mechanism of film formation from an aqueous polymeric
dispersions is quite complex, but can be briefly described in the
following steps:
1. Rapid evaporation of water, causing the particles of dispersed polymer to be
brought into close contact with one another.
2. Development of pressures “associated with capillary forces within the
structure”, that overcome repulsive forces between particles and cause
deformation of the polymer particles.
3. Gradual coalescence of the polymer particles as a result of the viscous flow
and movement of polymer molecules across the interfaces between particles.

• This process of film formation is very sensitive to process conditions used during
film coating.
• The coalescence of the latex particles will be very much dependent on free
volume (Which influences the movement of polymer molecules between
individual latex particles).
• Consequently, aqueous polymeric dispersions must be processed at
temperatures in excess of the glass-transition temperature of the polymer (or
plasticized polymer in the case of, e.g., ethylcellulose).
• Thus, the optimum processing conditions for aqueous polymeric dispersions
occur over a narrow range of temperatures. This explains why tackiness is a
common problem cited when film coating with such aqueous dispersions.

• Typical design of the coating machine:

• Typical behavior of tablet bed temperature and
moisture content over the process time :

• Video of film coating process.

3. Process parameters to consider
I. Geometrics of system components.
II. System pressures.
III. Process temperature.
IV. Spray rate and batch size.
V. Pan speed.

I. Geometrics of system components.
• Five spraygun positionings to be fixed:
• I) Gun-to-bed distance:
– Production scale: approx. 15 – 20 cm,
– Lab scale: approx 10 cm

• Overlapping demonstration:

II) Gun-to Gun distance:
Place periodically, not too close together
to avoid the possible overwetting
resuting from overlapping..

III) Gun-to-wall distance:
• Accurate positioning up, saves cleaning
work !

II. System pressures
• Spray gun pressure adjustments:
1. Atomizing air (AA)
- creates the fumigation.
2. Fan air (FA),
sometimes named “control air” (CA)
- creates the form of the pattern, (round or oval).
• 3. Needle air (NA),
- closes the liquid line.

• Influence of fan air adjustment:

III. Process temperatures
• Process temperatues to consider:
1. Intake
2. Exhaust.
3. Tablet bed.
• Exhaust temp is a function of:
- Intake Temperature
- Spray rate
- Process air volume
- Atomizing Air pressure.
- NB: If any of these parameters vary, the exhaust
temp varies as well, so exhaust temp. is used as a
process control variable by almost all systems.

• Tablet bed surface temperature is the
most critical of all temperatures…
Because exactly here is happening the most
important process detail:
The film forming

• Tablet bed temperature distribution:

IV. Spray rate and batch size
• The higher the spray rate and the
bigger the batch size the more
efficient is the process.
• Possible spray rate depends on:
- Drying efficiency of equipment.
- Core properties.
- Film properties.
- Quality of machine set up.

• Correlation between batch size and required process
time to apply 3% weight gain:

V. Pan Speed
• Factors governing pan speed:
1. Pan diameter.
2. Amount and type of baffles.
3. Tablet load “batch size”.
4. Tumbling behavior of the core substrate.

• Practical hints:
- Pre-heat with jog mode
(or even more gentle: manually)
- Pan speed as low as possible at process beginning,
but tablets MUST flow constantly.
- Permanently increase pan speed in small steps over
the complete process time.
- Cool down under slow permanent rotation.

V. Problems in film coating
• Unavoidable attritional effects demand that both the product being coated
and the coating itself be formulated with appropriate mechanical properties if
problems associated with fragmentation (of the cores) and erosion (of the
cores and coating) are to be avoided.
• The use of aqueous-based coating systems increased the complexity of the
process, as water has a significantly higher latent heat of vaporization (than
the previously used organic solvents). and thus greater attention must be
paid to monitoring (and preferably controlling) the drying conditions in the
aqueous process.
• Factors governing the interaction between a film coating and a substrate are:
1. Core characteristics : porosity, surface rugosity & surface energy all
affect wetting by the coating liquid.
2. Coating liquid characteristics: viscosity & surface tension affects the
initial wetting process of the substrate
3. Stresses that form within the coating, which are related to:
I. Shrinkage phenomena that develop as the coating dries.
II. Expansion/contraction of both coating and substrate while subjected to
heating and cooling cycles in the process.
III. Other core expansion factors (as swelling due to moisture absorption).

a. Picking
• Cause:
• When the coating on two adjacent tablets is not sufficiently dry before they get
in contact and adhere due to the very tacky nature of the partially dried
coating, and break apart later “issue of overwetting”
• In extreme cases, tablets with flat surfaces or flat edges may
permanently become glued together, named “twinning” or buildup of
multiplies.
• Overwetting occurs typically when the spray rate is excessive for the
drying conditions in the process.
• Localized overwetting results when:
1. insufficient number of spray guns is used so that certain regions got higher
conc. of coating liquid than other regions.
2. When one or more nozzles in a multiple-gun setup got blocked, causing all the
coating liquid to be channeled to the remaining guns.
• Coating formulations more likely to exhibit picking are those of HPC,
many of the enteric-coating formulae, acrylic aqueous latex-coating
systems due to their tackier property.

b. Roughness “Orange Peel”
• Cause:
• Certain process conditions are likely to induce surface roughness
“orange peel”, such conditions include low spray rates coupled with
excessive drying conditions, “high processing temperature and
airflows” and use of excessive atomizing air pressures which
accelerates premature drying of the droplets of coating liquid.
• The problem may be further complicated by spraying coating liquids
of excessively high viscosities.
• It’s critical that the droplets of the coating liquid dry
very soon after they make contact with the surface
of the product being coated.
• Generally, all film coated tablets exhibit the Orange
peel effect, but optimized coating processes will
allow this characteristic to be kept at a minimum
such that it’s not visible to the naked eye.

c. Edge wear “Chipping”
• Usually appear as fractures at the tablet edges due to their
exposure to the attritional effects while processing in the
coating pans.
• Cause:
1. Tablet cores having high friability values.
2. Worn tablet punches (produce “flashing” on the tablet edges).
3. Minor lamination problems (with the tablet cores) which induce edge
erosion problems to get worse.
4. Brittle film coatings that offer insufficient protection to tablet edges

d. Film cracking
• Cause:
• Occurs when the internal stress “that develops within the coating on
drying” exceeds the tensile strength of that coating.
• Cracking may be simple to catastrophic, especially when the
coating film tends to serve in the alteration of the release of
the API from the substrate.
• The problem is certainly exacerbated by thermal expansion
effects, particularly when significant differences exist
between the thermal-expansion coefficients for the core and
the coating respectively.

e. Bridging of logos “Intagliations”
• Cause:
• Internal stress is the major causative factor in logo bridging.
• This phenomenon occurs when a component of the internal stress becomes
sufficiently high so as to cause partial or complete detachment of the coating
(from the substrate) in the region of the logo.
• As a result of such detachment, the film is able to "shorten" and thus partially
relieve the stress within the film, In doing so, legibility of the logo can be
significantly reduced.
• Typically. this type of problem becomes
progressively worse as more coating
is gradually applied during the process.
• Solutions may involve:
1. improving film adhesion and/or reducing stress within the film.
2. require some reformation of either the tablet core or the coating.
3. appropriate design of tablet punches (especially with respect to the logo) may
help to alleviate the problem.
4. adjustment of process conditions

f. Film peeling
• Cause:
• On occasion (particularly during application of aqueous-coating
formulations). if cohesive failure (cracking) of the coating occurs, that coating
may subsequently peel back from the surface of the substrate.
• while both cohesive and adhesive failure are implicated here (both
phenomena being linked to internal stress).
• appropriate solutions typically involve addressing the initial cracking
problem by increasing the mechanical strength of the coating.

g. In-filling of logos
• Cause:
– in -filling of logos typically occurs during the spray application
of aerated aqueous film-coating solutions.
• When a foamy coating solution impinges on a regular part of
the tablet surface it will, under the shear forces generated,
form a film with "normal“ characteristics. However, those
droplets of coating liquid that reside in the logo, being
protected from the shear forces at the surface, gradually dry
to form a solid foam that eventually obliterates the logo.
• when the viscosity of coating solutions is too high, libration of
the foam (on standing) does not occur. Thus, the coating
liquid that is sprayed on during the coating process will still
be extremely aerated.

Summary of Advantages vs.
Disadvantages of Sugar Coating
1. Raw materials are inexpensive and
readily available.
2. Raw materials are widely accepted
with few regulatory problems (with the
exception of perhaps colors)
3. Inexpensive, simple equipment can be
used.
4. Sugar-coated products are esthetically
pleasing and have wide consumer
acceptability
5. The process is generally not as critical
(as film coating) and recovery (or
rework) procedures are more readily
accomplished
1. The size and weight of the finished product
results in increased packaging and shipping
costs.
2. The brittleness of the coatings renders the
coated tablets susceptible to potential
damage if mishandled.
3. The achievement of high esthetic quality
often requires the services of highly skilled
coating operators.
4. The final gloss is achieved by a polishing
step which can make imprinting difficult
5. The inherent complexity (from the
standpoint of the variety of procedures and
formulations used) of the process makes
automation more difficult

Process of Sugar Coating
1. Sealing:
– Offer initial protection to the tablet cores and prevent migration of core
ingredients to the coating layer.
– Sealing is done using application of polymer-based coating (eg: Shellac, Zein,
HPMC, PVAP & CAP) …. Made at 30% w / w conc. in an appropriate organic
solvent, preferably denatured ethanol.
– Because sealing polymers are water-insoluble, the layer must be minimized to
avoid the alteration in the API release.
– IF the final product is to have enteric properties, the use of enteric polymers as
PVAP or CAP for seal coat is preferable, ensuring that sufficient coating material
is applied.

2. Subcoating:
– Provides the means for rounding off the tablet edges and
building up the core weight.
– provides the foundation for the remainder of the sugar-coating
process. with any weakness in the final sugar coat often
being attributable to weaknesses in the subcoat.
– Subcoating formulations almost always contain high levels of
fillers such as talc. calcium carbonate. Calcium sulfate, kaolin,
and titanium dioxide, beside auxiliary film formers as acacia,
gelatin, or one of the cellulose dvs to improve the structural
integrity of the coating.
– It’s very critical during subcoating to get effective coverage of
the coating material over the tablet corners and on the
edges…”Tablet shapes play a critical role”.

3. Grossing “Smoothing”
• Assure the smoothness of the substrate, free from
irregularities prior to the application of the color coat.
• Depending on the degree of smoothing required, the
smoothing coating simply consists of a 70% sugar syrup,
containing titanium dioxide as an opacifier, may be with
other colorants to make a good base for the subsequent
color coat.
• If the substrate to be smoothed requires excessive work,
as in case which subcoat tablets have a pitted surface,
other additives as calcium carbonate, talc or corn starch
may be used in low conc. to enhance and accelerate the
smoothing process.

4. Color Coating:
• Has the most impact on appearance of the substrate.
• Occurs using either water-soluble dyes or water-insoluble pigments in sugar-coating
syrups.
• Using pigments has solved many coating defects caused by the soluble dyes “mottling,
variation in color from batch-to-batch, a skilled operator & light sensitivity with
subsequent fading by time”.
• Color properties is optimized using opacifiers as titanium dioxide.
• Most efficient process of color coating involves the use of predispersed, opacified lake
suspensions, with controlling ratios of lake & opacifier, various shades can be produced.
• If using pigments, careful attention must be paid to the pigment dispersion process,
otherwise specking in colour would be produced.
• It’s inadvisable to keep coating systems containing lakes “typically acidic” hot, otherwise
excessive amounts of inverted sugar will be formed

5. Polishing “Glossing”:
• Polishing is a step achieving the gloss that is typical of finished sugar-coated
tablets.
• generally recommended that tablets should be trayed overnight (prior to
polishing) to ensure that they are sufficiently dry.
• Excessively high moisture levels in tablets submitted for polishing will:
1. Make achievement of a good gloss difficult
2. Increase the risk of "blooming" and "sweating" over longer periods of time.
• Glossing or polishing can be carried out in various types of equipment (e. g..
canvas- or wax-lined pans), including that used for applying the sugar coating
itself.
• Polishing systems that may be used include:
1. Organic-solvent-based solutions of waxes (beeswax, carnauba wax, candelilla wax)
2. Alcoholic slurries of waxes
3. Finely powdered mixtures of dry waxes
4. Pharmaceutical glazes (typically alcohol solutions of various forms of shellac, often
containing additional waxes)

5. Printing:
• Typically, such printing involves the application of a pharmaceutical branding ink to
the coated tablet surface by means of a printing process known as offset
rotogravure.
• Adhesion of printing inks can be enhanced by application (prior to printing) of a
modified shellac, preprint base solution.

Basic application procedures of
sugar coating
1. Application of an appropriate volume (sufficient to completely cover the surface of every
tablet in the batch) of coating liquid to a cascading bed of tablets.
2. Distribution of the coating liquid uniformly across the surface of each tablet in the batch.
3. Drying of the coating liquid once uniform distribution is achieved.
• NB: the main mechanism for coating liquid distribution relates to the shearing action that
occurs as tablets cascade over one another, so it is not necessary to finely atomize the
coating liquid in order to ensure effective distribution of that liquid.
• It’s not necessary for each tablet to pass through the zone of application, unlike the film-
coating process.

Coating of pharmaceutical dosage forms

Recomendados

Recomendados

Más contenido relacionado

La actualidad más candente

La actualidad más candente (20)

Destacado

Destacado (20)

Similar a Coating of pharmaceutical dosage forms

Similar a Coating of pharmaceutical dosage forms (20)

Último

Último (20)

Coating of pharmaceutical dosage forms