Sugar Coating

Reasons for coating:

1. Extending shelf life
2. Taste masking
3. Easier to swallow
4. Mask batch differences
5. Rapid identification
6. Facilitates handling and packaging
7. Reduce cross contamination
8. Functional film coating to modify release
9. Aids in sales appeal
10. Avoid chemical compatibilities
All sugar-coated tablets are IR unless otherwise is specified.
Fixed dose combination → combining 2 APIs in the same dosage form
so that the patient takes one tablet instead of two different ones at the
same time, achieved by film coating
Dual release system → 2 patterns of release for the same API within the
same tablet, so that the patient takes one dose through the whole day,
achieved by film coating

Steps of Sugar coating:

#1: Sealing (wt gain 1-2%): using a hydrophilic insoluble sealant
dissolved in an organic vehicle, examples:
- Shellac resin + PVP (to prevent hardening)
- Cellulose acetate phthalate
- Polyvinyl acetate phthalate
- Acrylate (methacrylic acid + methyl methacrylate)
- Zein (alcohol soluble)
 - To prevent tablet core softening or disintegration in sub-coating
process
- Concentration has to be 15-30%, over that becomes very viscous,
non-sprayable and non-spreadable
Sub-coating (wt gain 50-100%):
- Accomplished by:
1. Application of gum/sucrose solution followed by dusting
powder
2. Application of suspension of dusting powder followed by
drying → preferred because of less sticking and twinning,
automated, doesn’t depend on operator skills
- Sucrose based solution containing gum (acacia/gelatin/starch) +
fillers:
o Calcium carbonate
o Kaolin
o Talc
o Titanium dioxide
o Calcium sulfate
- Rounding and shaping the tablet
Smoothing (wt gain 5-10%):
- Dilute syrup
- Fill in any imperfections from sub-coating
Color coating:
- Water soluble dyes
- Water insoluble pigments (preferred) (suspension)
- Water insoluble lakes (suspension)
- Give the final color of the tablet
Polishing:
- Beeswax or carnauba was dissolved in organic solvent
 - Attractive appearance
Printing:
- Special edible inks
- Identification purposes

Ideal characteristics of sugar-coated tablets:

- Perfectly smooth, rounded contour, even color coverage, high
gloss, distinct printing without smudging or breaking

Sugar coating process and equipment must provide:

1. Even distribution of coating liquid
2. Continuous mixing
3. Continuous drying throughout the whole process
4. Removal of any vapor or dust

Sugar Coating Equipment:

Traditional sugar-coating pan contains:
1. Circular metal pan rotates horizontally
2. Drying air supply (thermostatically controlled)
3. Fan assisted extract to remove dust and air
- Drying is not efficient
Immersion sword System:
- Contains a perforated sword immersed in the tablets bed so the air
is more intimately mixed with the wetted tablets for higher drying
efficiency
Perforated Pan Systems:
1. Driacoater: partially perforated ribs design
o drying is from the bottom of the bed to the top
o spraying from the top
o air suction from the center
o perforated ribs for mixing and introducing drying air
o air mixes the tablets and dries at the same time
o no need for baffles
o no dead spots
2. Hi-coater: partially perforated pan design
o contains baffles for mixing
o drying air and coating sprayed from the top
o air suction from the bottom
3. Accela-Cota: fully perforated pan design
o drying air from above and is suctioned from below the tablet
bed through the perforated rotating pan
o spraying also from above
o anti-slide baffles to improve mixing

Methods of Applying Coating liquid;

1. manually using a ladle (quality of tabs depends on skills of
operator)
2. peristaltic pump
3. atomizing systems (spraying) (reduced drying time, faster and even
distribution of coating liquid, applied in all three coating machines)
Spraying techniques:
1. Pressure (airless atomization) → for organic solutions
2. Air-spray atomization → for aqueous dispersions, we need air
pressure with aqueous solvents due to higher surface tension
 Film Coating
Polymeric films could be:
- Organic solutions
- Aqueous solutions
- Aqueous dispersions (for extended release and EC with pH
dependent release) (could be suspension or emulsion)
**Most important step in the production is film formation process,
resulting in differences in film structure, appearance, permeability,
thermal treatment requirement and modifying the drug release pattern.
Advantages of using Aqueous dispersions over organic solutions:
1. Low viscosity and less tackiness
2. Reduction of cost (no need for explosion proof equipment)
3. Solvent residues are less worrying
4. Toxicity hazards
Film formation steps:
1. Spraying
2. Deformation of droplets
3. Entanglement of polymer chain (brought by interfacial tension in
case of aqueous dispersions)
4. Gelling
5. Formation of continuous film when solvent evaporates
Reasons of using Plasticizers:
1. Swells and softens polymer spheres
2. Facilitates coalescence
3. Reduces MFFT and Tg
Thermal Curing step:
- Only when the film is a dispersion
 - Exposing the film coat to temp above MFFT for long time (45° for
8-12 hours or 70° for 1 hour)
- Aim → complete coalescence of and disappearance of individual
particle contours
Glass transition temp (Tg):
- Polymer undergoes change in material properties
- Below Tg → polymer is glassy
- Above Tg → rubbery polymer (amorphous)
Types of Polymers (based on solubility):
- Water soluble
- Water insoluble
- pH dependent solubility
NON-functional film coating is used to:
1. improve appearance
2. enhance stability
3. improve handling
4. taste masking
- Water soluble polymers are used
- Water insoluble and pH dependent polymers can be used in very
thin coating layers
Functional film coating → modify the release of API
Types of release:
1. Immediate release
2. Modified release
o Extended release (sustained or prolonged) (reduced dosing
frequency) (water insoluble polymers are used)
o Delayed release (enteric coated) (pH dependent polymer)
Film Formers:
1. Cellulose derivatives:
Polymer Notes
MC methyl cellulose -
Soluble

HPMC hydroxypropylmethylcellulose -
Water

HPC hydroxypropylcellulose -
HEC hydeoxyethylcellulose -
CMC carboxymethylcellulose -
Soluble in organic solvents,
EC ethyl cellulose available as aqueous dispersion,
Insoluble

produces reservoir type CR

Water

Soluble in organic solvents,

CA cellulose acetate produces reservoir type CR
Soluble in organic solvents,
CAB cellulose acetate butyrate produces reservoir type CR
Soluble in ethanol, aqueous
dispersion, soluble in water with
CAP cellulose acetate phthalate
(pH dependent solubility)

NH4OH, soluble in buffers

pH>=6.2
Enteric derivatives

Has 3 carboxylic acid groups,

CAT cellulose acetate trimellitate dissolves at pH=5.5, soluble in
water with NH4OH,
Soluble in mixtures of
HPMP hydroxypropylmethyl phthalate acetone/methanol, soluble in
buffer pH>=5
Dispersion of HMPCAS is used
HPMCAS hydroxypropylmethylcellulose for aqueous film coating, organic
acetate succinate solvents are also used, dissolves
in buffer pH>=6

2. Vinyl:
Polymer Notes
Soluble in many polar
soluble
Water

PVP polyvinyl pyrrolidone organic solvents, IR

(non-functional film)
PVA polyvinyl alcohol IR (non-functional)
insoluble
Water Soluble in most organic
solvents, produces
PVAc polyvinyl acetate reservoir-controlled
release systems (SR)
pH dependent solubility,
PVAP polyvinyl acetate phthalate used for EC

3. Glycols:
- High molecular wt PEG (6000-10 000)
- Water soluble
4. Natural Polymers:
- Zein → water insoluble, alcohol soluble
- Shellac → anion resin, used for EC
5. Silicone elastomers:
- Polydimethyl siloxane (OH terminated) → water insoluble, CR
6. Methacrylic acid copolymers: (pH dependent solubility)
Polymer Ratio Soluble at
Poly (methacrylic acid, ethyl acrylate) 1:1 pH>5.5
1:1 pH>6
Poly (methacrylic acid, methyl methacrylate)
1:2 pH>7
7. Methacrylate ester polymers: (water insoluble, yet permeable)
Polymer Ratio Permeability
Poly (ethyl acrylate, methyl methacrylate) 2:1 Medium
Poly (ethyl acrylate, methyl methacrylate, 1:2:0.2 High
trimethylamonioethyl methacrylate) chloride 1:2:0.1 Low
** chloride ion affects permeability, that’s why higher ratio gives higher
permeability.
** acetate → water insoluble
** phthalate → pH dependent solubility
** controlled release (CR) → use insoluble polymer of intermediate to low
permeability
Other components may be added to the coat, why?
- To improve film quality (plasticizer, surfactant, anti-tack agents)
- Modify the performance, permeability properties and appearance (pore
formers, channeling agents, opacifiers, coloring agents)

#1: Solvents (Liquid medium):

- Used as a vehicle to dissolve/disperse polymer + additives
- Ideal characteristics:
1. Colorless, tasteless, odorless, inexpensive, inert, non-toxic, non-
flammable
2. Allows easy dissolution and dispersion
3. Doesn’t give viscous systems at conc (2-10%)
4. Rapid drying rate
5. No environmental pollution
- Preferred solvent → water
- Organic solvents can be used (preferred if API is hydrolysable)
#2: Plasticizer:
- REQUIRED for films that are aqueous colloidal dispersions when MFFT is
above coating temp
- NOT REQUIRED for organic solutions (film is already dissolved down to
molecular level → already continuous)
- Organic solvents with high BP used to impart flexibility of hard polymers by
reducing cohesive intramolecular forces resulting in:
1. Reduction of tensile strength ‫القوة الالزمة لتكسير سالسل البوليمر‬
2. Increases flexibility
3. Reduces Tg and MFFT
4. Enhances coalescence and film integrity
- Water soluble plasticizers → they dissolve in the vehicle
1. Glycerin
2. Propylene glycol (PG)
3. Low m.wt. PEG (200-400)
4. Triethyl citrate (Citroflex®)
5. Surfactants such as tweens
 - Water insoluble plasticizers → have to be emulsified in the aqueous phase
1. ATEC (acetyl triethyl citrate)
2. ATBC (acetyl tributyl citrate)
3. DBP (dibutyl phthalate)
4. DBS (dibutyl sebacate)
5. DEP (diethyl phthalate)
6. TBC (tributyl citrate)
7. Oils (oleic acid, castor oil, coconut oil)
8. Surfactants such as Spans and Myavcet (acetylated mono glycerids)
#3: Surfactants:
- They exert their effect by reducing the surface tension between the solid and
liquid interface → thus enhancing the spreading of coating liquid and
enhancing the wetting of the surface.
- Two main types:
1. Endogenous: added during the polymerization process, could be latex or
pseudolatex (difference between them is the time when the surfactant is
incorporated)
2. Exogenous: added to the coating liquid after forming the polymer
- Main functions:
1. Stabilizing the formula: prevent agglomeration and coalescence of
polymer during shelf life, wet and homogenize the coating mixture
2. Enhance deposition of coating liquid on the surface of the substrate: act
as plasticizer
3. In case of controlled release, they increase the drug release rate of film
coated granules.
- Examples: Tweens. Cetyl alcohol, SLS, Myvacet (acetylated mono
glycerides), Pluronic.
#4: Pore Formers (channeling agents):
- For CR → impermeable or semi-permeable polymer + soluble pore former
- Examples: micronized sucrose, sorbitol, lactose, NaCl
#5: Anti-tacking agents:
- Tackiness: the ability of a polymer to adhere to a substrate
 - Tackiness id required for the polymer to adhere to the surface of a substrate
but to a certain level, exceeding that level will cause twinning and sticking
to the pan.
- Factors that affect tackiness:
1. Temperature (directly) → increasing temp increases tackiness
2. Plasticizer (indirectly) → high plasticizer content will decrease MFFT
and on the same temp (used when no plasticizer) will lead to increasing
tackiness.
- Example: talc (can be used up to 100% of dry polymer wt), kaolin, Mg
stearate, colloidal silica
- Application of anti-tacking agents:
1. Direct addition to the formula
2. Indirect (by mixing with wet coated pellets before drying)
#6: Colorants:
- Usually used → insoluble pigments. Why?
1. More chemically stable towards light
2. Better opacity and coverage
3. Contribute to impermeability (because they are insoluble)
4. Lesser migration risk during drying (because they are insoluble)
- May need the addition of opacifiers like (titanium dioxide & Ca carbonate)
- Examples:
1. Iron oxide pigments
2. Titanium dioxide
3. Aluminum lakes
4. Pearlescent pigments (contain mica)
5. Allura red
6. Indigo carmine
7. Tartrazine
8. Quinoline yellow
Coating Machines:
Fluidized bed coaters:
- Function by suspending a bed of solid particles in a moving gas
stream.
- Highly efficient drying systems
- Drying air → always moves upward (from bottom to top)
- Disadvantages:
1. Not suitable for friable cores and those prone to chipping and
edge abrasion
2. Not ideal for coating tablets
- Coating liquid is sprayed to the cores, depending on spraying
pattern, there are 3 types:
1. Top spray:
o Results in aggregation and growth (granulation)
o Sprayed liquid may get dried before reaching the cores,
resulting in non-continuous film formation, thus not suitable
for functional films
o Can be used for nun-functional films
2. Bottom spray:
o More contact between liquid and solid
o Suitable for functional films
3. Tangential spray:
o Spraying from the sides
o Has a rotary disc for mixing
o Suitable for spheronization and coating pellets

Coating process parameters:

** More expressed when using aqueous dispersions, because they
undergo more steps and take more time to achieve coalescent films
1. Product bed temperature:
- It is a function of balance/imbalance between heat input and output
(dissipation).
- Heat output (dissipation) is always less than input, why?
o Some heat will be used to elevate tablets temp
o Some heat will be also used to evaporate the liquid (latent
heat)
o Highest value of heat of dissipation is equal to the heat input
- What will happen when u spray hot or cold tablets?
➔ Low product bed temp: result in
o Drug migration into the film layer, because drying is
insufficient so the remaining liquid will dissolve the tablet.
o Incomplete film formation, because the temp is not sufficient
to overcome Tg and make the film flexible for continuous
film formation.
➔ High product bed temp: results in
o Faster evaporation due to very high temp → leads to
o Improper spreading (because the liquid is dried before
reaching the tablets) which will cause spots formation
o Increased sticking (because of the improper spreading →
high concentration of film on specific spots → sticking
o REMEMBER: elevated temp increases film tackiness
- Factors that are essential in controlling product bed temp:
1. Drying medium volume ‫طردية‬
2. Drying medium temp ‫طردية‬
3. Drying medium relative humidity (which affects drying
capacity) (higher humidity → less drying capacity)
4. Spray rate (amount of liquid delivered/time) ‫عكسية‬
o Higher spray rate (with all other factors held constant) → greater amount of liquid
delivered/time → lower product bed temp (and vice versa)
2. Spray Pressure:
- Atomization of the sprayed liquid
- Aims to reduce mean droplet size of polymeric solution
- If atomization pressure is high:
o Mean particle size is very small, liquid will evaporate very
rapidly and before reaching the tablets, so the polymer will
reach the tablets as solid particles leading to rough surfaces
(orange peel appearance)
- If atomization pressure is low:
o Mean particle size is very big, big localized droplets will be
formed and temp is not enough to evaporate the liquid
resulting in over wetting of parts of the tablets bed, which
will lead to sticking problems
- Solved by optimization.
- High viscosity solutions → need higher pressure
- Dispersions → low viscosity even at high concentrations → need
lower pressure
- Atomization of organic solutions is easier than aqueous solutions
due to lower surface tension

3. Coating Pan Speed:

- Affects intra-tablet coating uniformity
- Best coating uniformity → in spherical substrates (pellets) → no
special orientation
- Very high speed → no enough time for drying
- Very low speed → over-wetting and sticking
- Has to be optimized
4. Curing:
- Main purpose → to stabilize film coating from aqueous dispersions
- Coated dosage form is subjected to heat 10° above MFFT value
- Excessive curing → tackiness and agglomeration
** go back to the example in slides
Coating Defects:
Could be either:
- Due to process parameters defects
- Due to formulation defects
-
Defect Causes Solutions Notes
Capping → from top
Capping or bottom
and - - Lamination → layers
Revealed by
lamination friability test
- Reducing liquid
application rate.
Process defect → - Balancing pan speed Due to coating pan
Over wetting and spray rate. movement, twinning
Twinning - Increase drying air tablets will separate,
and picking temp and volume one of them will take
a layer from the
- Increase anti-tacking other (picking)
Formulation defect →
agent
Excessive film tackiness
- Reduce plasticizer level

Aqueous Dispersion:
Effect of spray drying (rapid - Reducing atomization
drying of coating liquid) pressure to obtain larger
Difficulty in spreading due to droplets Both problems can
high surface tension be solved also by
Roughness / moving spraying
orange peel Organic Solutions:
- Increasing atomization nozzles closer to the
pressure to obtain tablet bed
Difficulty in spreading due to
smaller droplets
high viscosity
- Thinning the solution
Use of high conc of pigments
- Addition of surfactant

Bridging → film shrinkage - increasing plasticizer

during drying content or changing it
Bridging Filling → applying too much Formulation
and filling - monitoring fluid problem
solution resulting in thick
application rate and
film, fast application of film
thorough mixing
leading to over-wetting
 - increase tensile strength
by using high mwt
Cracking → across
polymers
the crown of the
Cracking / If the internal strength - reduce internal strength
tablet
splitting exceeds the tensile strength by adjusting plasticizer
Splitting → around
type and concentration,
the edges
and pigment type and
concentration
Cratering Coating liquid penetrates the By avoiding over
Usually occurs for
surface causing localized wetting, using anhydrous
(surface disintegration and disruption coatings, applying seal
hydrophilic cores
with aqueous coating
erosion) of the coat coat to the core

Improper mixing
Uneven spraying Use of lake dyes or
Color Insufficient coating pigments to eliminate
Process or
variation formulation defects
Migration of soluble dyes migration
Plasticizer

Press Coating
- Compaction of granular material around an already performed core
using compressing equipment
- Used for:
o Alternative for sugar and film coating in case of very water-
sensitive drugs
o Separation of chemically incompatible materials
(combination tablets in dual release)
o Delayed release tablets (colonic drug delivery)
- Success depends on:
o Using core material that develops reasonable strength at low
compression loads
o Coating material has to be in the form of fine granules of
narrow PSD and with good binding properties