Tablet

Coating
A Technical Review

®TMTrademark of The Dow Chemical Company (“Dow”) or an affiliated company of Dow

THE COATING PROCESS
A TECHNICAL REVIEW
METHOCEL

The following review of the process The Coating Solutions BLACK BOX MODEL

involved with aqueous polymeric Regardless of the delivery system, the coating solution
film coatings is offered for those must be formulated to have a sprayable solution viscosity. Heated Conditionned Air
(temp., flow rate, humidity)
not intimately involved in the Generally, this means a viscosity of the coating solution in the
range of 150-400 mPa•s, although higher viscosities may be Outlet Air temperature,
manufacturing process. possible under certain equipment conditions. Formulations
humidity

may contain optional surfactants, plasticizers, or pigments. Coating solution (flow rate,
To use aqueous coatings on different drug substrates, % solids, temp.)
These additional excipients can affect the viscosity of
consider the coating process, a simple, black box
the coating solution, but the major factor controlling the Tablet Load (batch)
thermodynamic model. Customers must monitor the Weight, Surface Area,
formulation is the viscosity of the polymer grade being used
amount of liquid being applied to the coating surface, the Resistance to Flow
and the concentration of polymer in the solution.
ability of the air to evaporate the material under the fixed
Atomized Air-flow rate,
conditions of air flow rates, humidity, air temperature, and temp.
A variety of solvents may be used with tablet coating systems
the tablet surface area.
of METHOCEL™ hypromellose. At its inception, organic
solvent systems of methylene chloride/alcohol blends
Heat In = Heat Out
were used. This allowed very fast drying at relatively low
temperatures or air volumes. (Cp, air) (AFR)(∆T) = (212°F-Tin)(Cp, Sol)+(Water vol)(Hvap)

Cp, air - heat capacity of air

AFR - air flow rate
In some cases, hydroalcoholic solvent systems are used ∆T - difference between inlet and outlet air temperature
where the water content in the solvent mixture may range Tin - initial temperature of coating solution
Cp, Sol - heat capacity of solution
from 20-80% by weight. Hvap - heat of vaporization

Hypromellose is not soluble in absolute alcohol but may be

applied if more than 20% water is included in the alcohol.
The use of alcohol/water solvents also allowed for relatively
fast coating but was slower than the methylene chloride/
alcohol system.

More recently, aqueous coating has become a preferred

choice. This did require increased air handling and heat
exchange to facilitate rapid coating. Aqueous systems can
be formulated at varying water or solids content depending
on the choice of polymer, molecular weight, and the use of
pigments. In general, the higher the coating solids content,
the faster the tablet may be coated.

01  Tablet Coating ®TMTrademark of The Dow Chemical Company (“Dow”) or an affiliated company of Dow Tablet Coating  02
J - Tablet coating

THE COATING FORMULATION

GUIDELINES

Typical formulation ingredients: VISCOSITY CONCENTRATION CHART LOW VISCOSITY Using ETHOCEL™ Premium Ethylcellulose
METHOCELTM E PREMIUM PRODUCTS IN WATER
Viscosity mPa•s @ 20°C // Concentration % of METHOCEL
TM Polymers
Polymer:
METHOCEL™ products tend to have the best clarity, color, The ETHOCEL™ polymers should be dissolved in a solvent
7 000
and film properties. METHOCEL™ products are available in a (or solvent blend) at approximately 10-15% solids. A
range of molecular weights. The viscosity of a 2% solution of 6 000
plasticizer (e.g. glycerine) may be added to the mixture. The
these products are available as 3, 5, 6, 15, and 50 mPa•s. following solvents are recommended:
5 000 • Ethanol
Solvent: • Methanol
4 000
• METHOCEL™ products can be formulated in organic, • Acetone
hydroalcoholic, and aqueous solvent systems. Each 3 000
• Chloroform and ethanol blend
solvent system has a specific impact on the coating • Ethyl lactate and ethanol blend
process. Any of the METHOCEL™ products may be 2 000 • Methyl salicylate and ethanol blend
formulated in these solvent systems. It is recommended, • Methyl salicylate
1 000
however, that METHOCEL™ products be used in • Toluene and ethanol blend
organic or hydroalcoholic systems where better polymer • Methylene chloride and ethanol blend
compatibility is desired. 0 2 4 6 8 10 12 14
• The viscosity-concentration relationship for different Spray coating can be used to apply a thin film coating of
METHOCEL™ E50 Premium LV
solvents varies slightly with the choice of solvents. ETHOCEL™ to the surface of tablets or non-pareils. The
The information in the figure here and the ones on METHOCEL™ E15 Premium LV solution is applied to the tablets or non-pareils using
page 5 and 6 may be useful in predicting polymer METHOCEL™ E5 Premium LV equipment such as a Wurster fluidized bed. The solvent
concentrations necessary to achieve sprayable coating evaporates, leaving a film coating of ETHOCEL™ polymer.
solution viscosities. Typical process temperatures include an inlet temperature
of 55-60° C, product temperature of 35-45° C, and exhaust
temperature of 30-40° C.

The coating thickness and release profile can be varied by

changing the number of passes through the fluidized bed.

Although it is not a true encapsulation process, time-release

capsules are often manufactured by spraying solutions of
ETHOCEL™ polymers onto small beads of active ingredients.
Wide variation of release rates or release patterns can be
achieved by varying polymer ratios and coating weights.

03  Tablet Coating ®TMTrademark of The Dow Chemical Company (“Dow”) or an affiliated company of Dow Tablet Coating  04
 VISCOSITY
CONCENTRATION
J - Tablet coating J - Tablet coating J - Tablet coating

VISCOSITY CONCENTRATION FOR METHOCELTM VISCOSITY CONCENTRATION FOR METHOCELTM VISCOSITY CONCENTRATION FOR METHOCELTM VISCOSITY CONCENTRATION FOR METHOCELTM
IN AN 80:20 WT/WT WATER ETHANOL MIXTURE IN AN 60:40 WT/WT WATER ETHANOL MIXTURE IN AN 40:60 WT/WT WATER ETHANOL MIXTURE IN AN 20:80 WT/WT WATER ETHANOL MIXTURE
Viscosity mPa•s @ 20°C // Concentration % of METHOCELTM Viscosity mPa•s @ 20°C // Concentration % of METHOCELTM Viscosity mPa•s @ 20°C // Concentration % of METHOCELTM Viscosity mPa•s @ 20°C // Concentration % of METHOCELTM

104 104 104 104

8 8 8 8
6 6 6 6
4 4 4 4
2 2 2 2

103 103 103 103

8 8 8 8
6 6 6 6
4 4 4 4
2 2 2 2

102 102 102 102

8 8 8 8
6 6 6 6
4 4 4 4
2 2 2 2

101 101 101 101

8 8 8 8
6 6 6 6
4 4 4 4
2 2 2 2

0 5 10 15 0 5 10 15 0 5 10 15 0 5 10 15
J - Tablet coating
METHOCEL™ E50 Premium LV METHOCEL™ E50 Premium LV
J - Tablet coating J - Tablet coating
METHOCEL™ E50 Premium LV METHOCEL™ E50 Premium LV
METHOCEL™ E15 Premium LV METHOCEL™ E15 Premium LV METHOCEL™ E15 Premium LV METHOCEL™ E15 Premium LV
METHOCEL™ E5 Premium LV METHOCEL™ E5 Premium LV METHOCEL™ E5 Premium LV METHOCEL™ E5 Premium LV

VISCOSITY CONCENTRATION FOR METHOCELTM VISCOSITY CONCENTRATION FOR METHOCELTM VISCOSITY CONCENTRATION FOR METHOCELTM VISCOSITY CONCENTRATION FOR METHOCELTM
IN AN 80:20 WT/WT METHYLENE CHLORIDE-ETHANOL MIXTURE IN AN 60:40 WT/WT METHYLENE CHLORIDE-ETHANOL MIXTURE IN AN 40:60 WT/WT METHYLENE CHLORIDE-ETHANOL MIXTURE IN AN20:80 WT/WT METHYLENE CHLORIDE-ETHANOL MIXTURE
Viscosity mPa•s @ 20°C // Concentration % of METHOCELTM Viscosity mPa•s @ 20°C // Concentration % of METHOCELTM Viscosity mPa•s @ 20°C // Concentration % of METHOCELTM Viscosity mPa•s @ 20°C // Concentration % of METHOCELTM

104 104 104 104

8 8 8 8
6 6 6 6
4 4 4 4
2 2 2 2

103 103 103 103

8 8 8 8
6 6 6 6
4 4 4 4
2 2 2 2

102 102 102 102

8 8 8 8
6 6 6 6
4 4 4 4
2 2 2 2

101 101 101 101

8 8 8 8
6 6 6 6
4 4 4 4
2 2 2 2

0 5 10 15 0 5 10 15 0 5 10 15 0 5 10 15
METHOCEL™ E50 Premium LV METHOCEL™ E50 Premium LV METHOCEL™ E50 Premium LV METHOCEL™ E50 Premium LV
METHOCEL™ E15 Premium LV METHOCEL™ E15 Premium LV METHOCEL™ E15 Premium LV METHOCEL™ E15 Premium LV
METHOCEL™ E5 Premium LV METHOCEL™ E5 Premium LV METHOCEL™ E5 Premium LV METHOCEL™ E5 Premium LV

05  Tablet Coating ®TMTrademark of The Dow Chemical Company (“Dow”) or an affiliated company of Dow Tablet Coating  06
 Evaluation of Films Containing J - Tablet coating
METHOCEL™ in Tablet Coating

J - Tablet coating

Many methods have been used and reported on the Film testing was done on an Instron, testing in 50% RH Most companies that coat tablets wish to use the lowest BLENDING CHART FOR METHOCELTM E5 AND E15 PREMIUM LV (USP)
(10% CONCENTRATION IN WATER)
evaluation of polymer films for tablet coating. Besides actual at 75°F. Measurement of tensile at break, work to break, viscosity possible to maximize production efficiency. Viscosity, mPa•s @ 20°C // %, METHOCELTM E15P LV / METHOCELTM E5P LV
tablet coating evaluations we have found that the physical elongation at break, and Young’s Modulus were recorded However, that there is a trade-off in physical properties with
210
evaluation of free films provides useful information. The and evaluated. We find that toughness is the best predictor lowering molecular weight. This is why METHOCEL™ is
200
following data and observations have been made through of overall film performance as it includes both the film seldom used alone as the coating polymer. 190
testing of 1 mil dry films made by casting on glass and drying strength and ability to deform without breakage. Young’s 180
at 50°C. While there is a substantial amount of data scatter, Modulus has been reported as useful in predicting adhesion. Reduction of film properties usually causes problems like 170
trends may be clearly seen when formulation parameters The lower the Young’s Modulus the better the film adhesion logo bridging or cracking. The level at which this becomes 160
150
were changed. to tablet substrates. a problem is very dependent on the tablet substrate,
140
geometry, and engraving. 130
FILM PROPERTIES OF LOW MOLECULAR WEIGHT FILM PROPERTIES OF LOW MOLECULAR WEIGHT 120
METHOCELTM E PRODUCTS METHOCELTM E PRODUCTS Although a wide variety of viscosity grades are available, 110
Tensile strength, psi // 2% Aqueous viscosity Work to break, psi // 2% Aqueous viscosity 100
intermediate viscosity grades may be available on request or
90
can be manufactured through blending.
80
16 000 2000 70
Blending Different Molecular Weight Grades of 60
14 000 50
METHOCEL™
12 000 1500 40
J - Tablet coating 30
10 000 J - Tablet coating has shown that wide blends of viscosity
Experimentation 20
8 000 1000 J - Tablet coating grades often give better results than the narrower molecular 10

6 000
weight distribution of a manufactured product. For example,
100/0 80/20 60/40 40/60 20/80 0/100
we have found that a blend of METHOCEL™ products
4 000 500 to achieve a nominal viscosity of 15 mPa•s generally 100% of 100% of
2 000 outperformed the typical ELV product. While blending of METHOCEL TM E5 METHOCEL TM E15
Premium LV Premium LV
product viscosities is usually not necessary, improvements
0 5 10 15 20 25 30 35 40 45 50 55 0 5 10 15 20 25 30 35 40 45 50 55 in coverage, cracking, or logo bridging may be achieved on
difficult tablet substrates.
Green area = 90% confidence limits based on Green area = 90% confidence limits based on BLENDING CHART FOR METHOCELTM E5 AND E15 PREMIUM LV (USP)
multiple lots of 5, 15, and 50 mPa•s products multiple lots of 5, 15, and 50 mPa•s products (5% CONCENTRATION IN WATER)
Viscosity, mPa•s @ 20°C // %, METHOCELTM E15P LV / METHOCELTM E5P LV

210
200
190
APPROXIMATE MOLECULAR WEIGHT/
180
VISCOSITY CORRELATION FOR HYPROMELLOSE, 20°C
Viscosity of a 2% aqueous solution, mPa•s @ 20°C // Molecular weight FILM PROPERTIES OF LOW MOLECULAR WEIGHT 170
FILM PROPERTIES OF LOW MOLECULAR WEIGHT
METHOCELTM E PRODUCTS (COMPARISON TO E5/E50P LV BLENDS)
METHOCELTM E PRODUCTS 160
Work to break, psi // 2% Aqueous viscosity
% Elongation // 2% Aqueous viscosity 150
140
105 130
2 000 120
30
110
104 100
1 500
90
20 80
70
1 000 1 000 60
50
10 40
100 500
30
20
10
0 5 10 15 20 25 30 35 40 45 50 55
100/0 80/20 60/40 40/60 20/80 0/100
0 5 10 15 20 25 30 35 40 45 50 55 0 1 000 104 105 106
Green area = 90% confidence limits based on 100% of 100% of
Green area = 90% confidence limits based on Mn=Number average molecular weight multiple lots of 5, 15, and 50 mPa•s products METHOCEL TM E5 METHOCEL TM E15
multiple lots of 5, 15, and 50 mPa•s products Mw=Weight average molecular weight Premium LV Premium LV

07  Tablet Coating ®TMTrademark of The Dow Chemical Company (“Dow”) or an affiliated company of Dow Tablet Coating  08
Effects of
Plasticizers

The use of plasticizers with Since the most common level of plasticizerJ - Tablet coating
in use today is The use of plasticizer also reduced the tensile strength of all The amount of plasticizer used is very important to film
about 20% based on polymer solids, we chose to evaluate the films. An evaluation of film toughness, however, shows properties. If the film is over-plasticized it will lose toughness
hypromellose film coatings is very a variety of plasticizers with hypromellose at that level. A that equivalent to improved performance was seen with the or may exceed the capacity of the polymer to hold the
common. However, many different control of METHOCEL™ with no plasticizer was included low molecular weight polyethylene glycols from PEG 300 plasticizer. For example, increasing the level of propylene
types have been reported in use. We for reference. As expected, most plasticizers made the films to PEG 1450. All of the plasticizers tended to reduce the glycol in a film of METHOCEL™ demonstrated that an
less brittle and increased elongation results. Interestingly, value for Young’s Modulus and may indicate an increase optimum level is 20-30% based on polymer solids. Levels
chose to evaluate the effect of various the higher molecular weight polyethylene glycols often in adhesion. Finally, in aqueous systems, it is generally of propylene glycol greater than this do not significantly
plasticizers on film properties of used in film coating actually decreased elongation. Other recommended that water-soluble plasticizers be used. In degrade film properties, possibly due to compatibility
METHOCEL™ as well as evaluate the plasticizers like oleic acid, triacetin, and propylene glycol nonaqueous systems, plasticizers like triethylcitrate, triacetin, limitations or volatility of the plasticizer. With the less volatile
(PG) had little effect. castor oil, acetylated monoglycerides, and oleic acid may be polyethylene glycol PEG 600 and PEG 1450, an optimum
optimum plasticizer level. preferred. is reached at 20-30% plasticizer based on polymer solids.
Beyond this optimum a continual decrease in film toughness
is experienced.
EFFECTS OF PLASTICIZERS ON METHOCELTM E5 PREMIUM LV FILMS (ELONGATION)* EFFECTS OF PLASTICIZERS ON METHOCELTM E5 PREMIUM LV FILMS (TOUGHNESS)*
% Elongation
Work to break, psi

25 800
90% Confidence Intervals 90% Confidence Intervals
700
20
600

15 J - Tablet coating 500

400
10
300

200
5
100

CONTROL PG GLYCERIN PEG PEG PEG PEG PEG PEG OA TRIACETIN CONTROL PG GLYCERIN PEG PEG PEG PEG PEG PEG OA TRIACETIN
300 400 600 1 450 3 350 8 000 300 400 600 1 450 3 350 8 000
* 15% METHOCELTM E5 Premium LV * 15% METHOCELTM E5 Premium LV
3% Plasticizer 3% Plasticizer
82% Water 82% Water

EFFECTS OF PLASTICIZERS ON METHOCELTM E5 PREMIUM LV FILMS (TENSILE STRENGTH)* EFFECTS OF PLASTICIZERS ON METHOCELTM E5 PREMIUM LV FILMS (YOUNG’S MODULUS)*
Maximum tensile strength, psi Work to break, psi

8 000 400
90% Confidence Intervals 90% Confidence Intervals
350
7 000
300
6 000
250

5 000 200

150
4 000
100
3 000
50

CONTROL PG GLYCERIN PEG PEG PEG PEG PEG PEG OA TRIACETIN CONTROL PG GLYCERIN PEG PEG PEG PEG PEG PEG OA TRIACETIN
300 400 600 1 450 3 350 8 000 300 400 600 1 450 3 350 8 000
* 15% METHOCELTM E5 Premium LV * 15% METHOCELTM E5 Premium LV
3% Plasticizer 3% Plasticizer
82% Water 82% Water

09  Tablet Coating ®TMTrademark of The Dow Chemical Company (“Dow”) or an affiliated company of Dow Tablet Coating  10
 Polymer
Blends
J - Tablet coating J - Tablet coating

It may at times be advantageous to Other polymer blends have been used at times by the This could be a method of increasing polymer concentration
industry. Blends of methylcellulose and polyvinyl pyrrolidone without detrimentally raising solution viscosity. Care should
blend polymers of varying types. (PVP) have been used commercially. While PVP has poor be taken, however, to evaluate the properties of the film or
film formation properties, it can be used at very high coated tablet to ensure successful formulation.
Hydroxypropyl cellulose (HPC), for example, has been used
concentrations with very low viscosity in water.
in film coating. While HPC typically is much more brittle
than hypromellose it does have the property of being a
better adhesive. Used alone the film may be tacky and cause FILM TENSILE STRENGTH OF BLENDS FILM ELONGATION OF BLENDS
problems in sticking or picking of tablets. But when used in OF METHOCELTM E5P LV HYPROMELLOSE/ OF METHOCELTM E5P LV HYPROMELLOSE/
HYDROXYPROPYL CELLULOSE* HYDROXYPROPYL CELLULOSE*
combination with hypromellose, the HPC product imparts
J - Tablet coating better adhesion. For example, when HPC-EF and HPC-LF
Stress at break, psi // % Hydroxypropyl cellulose % Elongation at break // % Hydroxypropyl cellulose

were added to METHOCEL™ in increasing concentrations,

7 000 6
the films lost strength, toughness, and became brittle. It was
noticed, however, that the films adhered very tightly to glass
6 000 5
plates. It was theorized and has been shown in practice that
the use of HPC in hypromellose films will increase adhesion. 5 000
4
This can be predicted from the reduction in Young’s
Modulus. We recommend that if adhesion needs to be 4 000
3
increased to solve problems such as logo bridging, that HPC-
3 000
J - Tablet
EF or -LF be used at a maximum of 25%coating
of the total polymer J - Tablet coating
2
solids. Additional amounts may weaken the films too much 2 000
to be useful.
1
1 000

EFFECTS OF PLASTICIZER CONCENTRATION 0 25 50 75 100 0 25 50 75 100

ON METHOCELTM E PREMIUM LV FILMS (TOUGHNESS)
Work to break, psi // % Plasticizer (w/w METHOCELTM Polymer)
* Films made from solutions containing 15% (w/w) total polymer solids * Films made from solutions containing 15% (w/w) total polymer solids

HPC-EF HPC-EF
2 500 HPC-LF HPC-LF

2 000
FILM STRENGTH OF BLENDS YOUNG’S MODULUS OF BLENDS
OF METHOCELTM E5P LV HYPROMELLOSE/ OF METHOCELTM E5P LV HYPROMELLOSE/
HYDROXYPROPYL CELLULOSE* HYDROXYPROPYL CELLULOSE*
1 500 Work to break, psi // % Hydroxypropyl cellulose Young’s modulus, psi // % Hydroxypropyl cellulose

1 000
300 300 000

500 250
260 000

200
220 000
0 10 20 30 40 50
150

METHOCELTM E50P LV/PEG 1450 METHOCELTM E5P LV/PEG 600 180 000
METHOCELTM E50P LV/PEG 600 METHOCELTM E5P LV/PG 100
METHOCELTM E50P LV/PG METHOCELTM E5P LV/PEG 1450
140 000
50

0 25 50 75 0 25 50 75 100

* Films made from solutions containing 15% (w/w) total polymer solids * Films made from solutions containing 15% (w/w) total polymer solids
HPC-EF HPC-EF
HPC-LF HPC-LF

11  Tablet Coating ®TMTrademark of The Dow Chemical Company (“Dow”) or an affiliated company of Dow Tablet Coating  12
 J - Tablet coating

Pigmented
Coatings

Very often it is desirable to apply To examine the effect of the plasticizer supplied in pigment EFFECT OF VARIOUS PIGMENT DISPERSIONS ON FILM PROPERTIES OF METHOCELTM E15 PREMIUM LV (TENSILE STRENGTH)
Maximum tensile strength, psi // % Propylene glycol (w/w) METHOCELTM E15 Premium LV
dispersions, a series of pigmented films was prepared using
opaque, pigmented coatings. pigment and METHOCEL™ at a ratio of 1 to 2. A variety of

CNP *
Pigmented coatings can provide commercial pigments were used and film properties plotted 13 000

additional light stability to dosage versus the amount of plasticizer contributed by the pigment
dispersion. A control unpigmented METHOCEL™ is plotted
forms and help differentiate tablets by 11 000

CNP *
as well.
color. Most pigments are supplied as

Spectracoat Apple Green

Warner-Jenkinson White
9 000

Opaspray Yellow
color dispersions in alcohol, propylene It is clearly seen that the pigmented films exhibit a distinct

Opaspray White

Spectracoat Orange
loss of strength from the unpigmented control. The very high

Chromakote White
glycol, or water. Pigments used in tablet levels of propylene glycol found in some of the pigment 7 000
coatings generally are either aluminum dispersions did not detrimentally affect film strength.
lakes or iron oxides, with titanium 5 000
Normally, pigmented films are formulated with additional
dioxide and talc used in white or pastel plasticizer even though there may be an excess available
colors. from the pigment dispersion. To evaluate the effect of 3 000
additional plasticizer, an additional 20% polyethylene glycol
When pigments are used in tablet coatings they have a 600 (PEG 00) was added to the pigmented film coatings. In
significant effect on the film properties. As with any plastic, every case an increase in film properties was noted with the 0 10 20 30 40 50 60 70 80 90 100
when pigments are added a reduction in flexibility and additional plasticizer. This strongly suggests the use of the
strength is usually experienced. Additionally, because the optimal 20-30% additional polyethylene glycol plasticizer Films cast from solutions of 5% (w/w) METHOCELTM E15 Premium LV.
METHOCELTM E15 Premium LV to pigment solids is 2 to 1.
pigments are usually dispersed in a plasticizer like propylene when formulating pigmented films.
glycol, the plasticization effect may be entirely dependent *CNP= Control No Pigments

on the ratio of pigment to polymer used in the formulation.

In the plasticizer section of this brochure it was shown that
additional levels of propylene glycol in an unpigmented film Microbiological Considerations Use of METHOCEL™ in Sugar Coatings
did not necessarily lead to reduced film properties.
When working with aqueous solutions, the possibility of METHOCEL™ products have found application in sugar
microbiological contamination is a valid concern. It has coatings as a seal coating or as a film modifier. As a
EFFECT OF ADDING PEG 600 TO PIGMENTED METHOCELTM E15 PREMIUM LV FILMS (TOUGHNESS) been reported in the literature that many cellulose-based subcoating, METHOCEL™ can be used with or without
Work to break, psi // % Propylene glycol (w/w) METHOCELTM E15 Premium LV
polymers can support microbiological growth. With cellulose plasticizer to place a protective layer over the tablet core.
Opaspray Yellow
Warner-Jenkinson White

ethers the higher the level of chemical substitution, the more In cases where additional protection from moisture is
Spectracoat Orange
Chromakote White

resistant to enzymatic breakdown the polymer becomes. desired, ETHOCEL™ ethylcellulose can be combined with
1 000
METHOCEL™ products have a relatively high level of METHOCEL™ in a co-solvent blend of methylene chloride/
substitution but will support microbiological growth in the alcohol and applied to the tablet cores. At 25% ETHOCEL™
Opaspray White

800
very low viscosity grades. It is therefore important to take and 75% METHOCEL™, little effect is seen on drug
reasonable care in the preparation of coating solutions to dissolution. At higher levels of ethylcellulose (e.g., >75%)
keep all the equipment and excipients clean. Usually GMP a delay in drug diffusion is experienced. METHOCEL™
600 standards will suffice. METHOCEL™ Premium products products may be used in sugar coatings to reduce coating
Spectracoat Apple Green

are supplied to meet USP guidelines for microbiological brittleness. Compatibility is improved if the polymer is fully
attributes and are certified to be free of the USP pathogenic hydrated before the addition of sugar. Use of corn syrup
400 organisms. The production process for METHOCEL™ for some of the sugar solids will also improve polymer
products is essentially self-sterilizing so no significant compatibility in sugar systems. These hypromellose polymers
contamination of METHOCEL™ has ever occurred. may also replace the conventional use of acacia and/or
200 gelatin in sugar coatings.
It is normally recommended that aqueous solutions be made
and used within one week’s time. Additional protection can
be obtained by the use of preservatives like propylparaben
0 10 20 30 40 50 60 70 80 90 100
or methylparaben or the addition of alcohol to the solution.
Films cast from solutions of 5% (w/w) METHOCELTM E15 Premium LV.
METHOCELTM E15 Premium LV to pigment solids is 2 to 1.

13  Tablet Coating ®TMTrademark of The Dow Chemical Company (“Dow”) or an affiliated company of Dow Tablet Coating  14
Production
Considerations

Preparation of the Coating Solution Foaming Air Atomization Pressure and Flow Rates Fluid bed coating of tablets may also be desirable for certain
Proper preparation of the coating solution is necessary Solutions of METHOCEL™ products have a tendency to The amount of air being applied and the amount of pressure formulations. A variety of fluid bed coating equipment is
to achieve good coating in a reasonable amount of time. foam under agitation because these polymers are surface being utilized to atomize the liquid droplets can determine manufactured with many application methods such as top
METHOCEL™ polymers are supplied as a fine powder active. Air entrapped in ingredients or that is introduced by the efficiency and effectiveness of the coating system. It spray, bottom spray, side spray, and tangential rotary spray.
and will rapidly hydrate in cold water. The hydration is so excessive agitation can increase this tendency. However, is important to make the smallest possible droplet size to Fluid bed equipment is available from Glatt Air Techniques,
rapid that without proper agitation, clumps of gels with dry once foaming had occurred, it can be reduced by defoamers ensure rapid drying. Air atomization is generally preferred Vector Corporation, and Aeromatic, as well as other
powder inside can form. Once formed, additional agitation like Dow Corning AF products or by settling over time. with aqueous systems because it enhances initial liquid companies.
and time are needed to completely hydrate all the polymer. evaporation. Small droplets are necessary to achieve a fine,
Several methods are useful in aiding the timely preparation When mixing solutions, the level of agitation should be smooth surface on coating tablets. Changes in air flow rates The volume, temperature, and humidity of the drying air
of coating solutions. changed as thickening occurs. Agitation should move the and air atomization pressure can affect delivery rates when are critical in optimization of the coating process. Generally
fluid surface in the vessel and start to pull a small vortex. using a system other than a positive displacement pump. it is desirable to deliver the greatest possible amount of
• Dispersion in hot water. Since METHOCEL™ products As thickening occurs, the agitator speed will need to be air at the desired 70-90°C temperature without causing
are not soluble in hot water, lump-free dispersing can increased to maintain sufficient mixing. Proper blade Spray Systems over-fluidization of the tablet bed. Often older equipment
be easily accomplished by dispersion in hot water. placement and baffling are necessary so consultation with The numbers and types of spray nozzles utilized in any is limited by air handling capacity or heating capacity.
Temperatures in excess of 80°C are recommended, equipment suppliers is recommended. A quiescent period of coating pan are of critical importance and information Therefore we recommend measurement of air flow rates
but even temperatures of 60-80°C will slightly aid the 15-45 minutes is usually recommended after mixing to allow should be obtained from the equipment manufacturer. and consultation with equipment manufacturers if coating
polymer dispersion. The polymer dispersion is then most of the entrapped air to move to the surface. It is particularly important that nozzles be selected that can capacity appears limited. Air flow rates should be monitored
cooled to cause polymer hydration. The cooling may be achieve a proper pattern for uniform coating of the tablet during the coating process as exhaust air filters can become
accomplished externally in jacketed vessels or part of Filtration surfaces. Nozzle fan angles, the number of nozzles, and the restricted with over-spray, dust, and tablet particles.
the water may be reserved as cold water and added after It is often beneficial to subject coating solutions to filtration. distance from the tablet bed must be optimized so uniform
polymer dispersion. This ensures that any lumps or incompletely hydrated side-to-side coating of the tablet bed is achieved without The condition of inlet air also affects the drying capacity.
• Blending of ingredients. Another method to minimize polymers are removed. Use of a 60 to 80 mesh screen can tending to overwet tablets or spray dry the solution. We High humidity air dries tablets less effectively than dry
polymer agglomeration consists of separating polymer normally be accomplished with commercial filtration devices. recommend customers seek information from both the air. Thus a process optimized for one day’s atmospheric
particles by dilution with other coating excipients. Gravity flow is possible, but air pressurization is preferred for equipment manufacturers for nozzles and coating pans for conditions may need daily adjustment if the inlet air is not
Combinations of dry pigments, dry plasticizer, and rapid filtration. further information. conditioned and controlled.
polymer can often be added directly to process water.
• Dispersion in a nonsolvent. When formulating Application Rate Coating Equipment Normally, inlet air is controlled to the range of 70–90°C.
hydroalcoholic or organic solvent coatings of The rate of coating solution delivery is an important process Modern film coating pans are manufactured by a variety Higher or lower temperatures may be desired for specific
METHOCEL™, solutions are easily made by dispersing control variable. While fast application of the coating solution of suppliers. Each supplier has its own configuration temperature-sensitive products or for fast coating
the polymer in alcohol (a non-solvent) and then is important to minimize batch times it must be remembered for the coating operation. Basic differences revolve application.
hydrated by the addition of water. In organic systems there are limitations for each type of equipment and coating around movement of air through the tablet bed. Some
METHOCEL™ can be dispersed in alcohol and then solution being utilized. Practical limits can be determined manufacturers move air upward through the tablet bed while The Tablet Load
hydrated by the addition of methylene chloride. by utilizing the basic thermodynamic relationships and others pass the air downward through the fluid bed. Some The pan loading and tablet dimensions will also affect
• Direct addition to room temperature water. This method, monitoring exhaust air temperature. The flow rate of pans are fully perforated around the entire circumference coating efficiency. Most coating pans must be filled to an
while the most difficult, is often used in large scale coating solutions is generally controlled by a positive while others have areas or regions of perforation. While there operative volume for tablet coating. Too few or too many
coating operations due to equipment and heat transfer displacement pump, although other coating systems may are some basic differences between these designs, each tablets lead to inconsistent coating quality. Even the shape of
limitations. METHOCEL™ products may be added rely upon an air pressure pot delivery system. When using has its own beneficial features and can be effectively utilized tablets will affect the optimal loading and drying efficiency of
directly to process water if a slow controlled addition of positive displacement pumps, viscosity of the coating for aqueous film coating. Some of the typical manufacturers the coating operation. Care must be taken in selection of the
the polymer is used in combination with good agitation. solution is not a critical factor in the flow rate. However, of equipment today are: Driam of West Germany, Thomas tablet shape to be coated. Friable tablets or soft tablets may
Care must be taken to control the agitation level to when using a pressure pot delivery system, the viscosity of Engineering, Vector Corporation, and Key Industries in the be very difficult to coat. Tablets using a high level of waxy or
minimize foaming and allow sufficient time for complete the coating solution will affect the delivery rate. It should U.S. hydrophobic ingredients may be difficult to coat due to poor
polymer hydration. also be recognized that the temperature of the coating adhesion or poor wetting.
solution will affect viscosity of the coating solution. As with
most polymers, when the solution temperature increases
(while staying below the thermalgelation temperature) the
coating viscosity will decrease. The application of shear to
concentrated polymer solutions can also reduce viscosity.

15  Tablet Coating ®TMTrademark of The Dow Chemical Company (“Dow”) or an affiliated company of Dow Tablet Coating  16
Safety
Considerations

METHOCEL™ cellulose ether products Storage Disposal

In storage or use of any dusts or fine powders, good Dow studies show that METHOCEL™ cellulose ether
resemble naturally occurring plant housekeeping is required to prevent dusts in air from products do not biodegrade (that is, they show no 5-, 10-,
and seaweed gums in many of their reaching possibly explosive levels. or 20-day BODs) in aquatic environments. They should
chemical, physical, and functional therefore present no ecological hazard to aquatic life.
Caution Since METHOCEL™ cellulose ether products and their
properties since all these materials Under certain conditions, a fine dust of this material in air formulations present no significant ecological problems
possess a basic carbohydrate structure. may cause a dust explosion when exposed to heat, sparks, or they can be disposed of by industrial incineration or in an
open flame. The National Fire Protection Association’s NFPA approved landfill, providing all federal, state, and local
Gums have a long history of use in food and pharmaceutical 654, “Standard for the Prevention of Fire and Dust Explosions regulations are observed. Dow recommends that the
products. METHOCEL™ cellulose ether products have had in the Chemical, Dye, Pharmaceutical and Plastic Industries,” material be buried in an approved landfill; incineration
extensive evaluation and testing in both acute and long-term should also be followed. should be done under carefully controlled conditions to
feeding studies in a number of species, including humans. avoid possibility of dust explosion.
Their use as food additives in a wide variety of food items With METHOCEL™ cellulose ether products with particle
and their broad use in pharmaceutical products attest to the sizes of 74μ or less (finer than 200 mesh), critical levels are Customer Notice
safety of METHOCEL™ Premium cellulose ether products. reached at concentrations of 28 gm/m3 (0.03 oz/ft3). The Dow strongly encourages its customers to review both
minimum ignition energy to cause a dust explosion is in the their manufacturing processes and their applications of
Dow has been making cellulose ethers for pharmaceutical range of 28 mJ. Static of a human body has about 25 mJ. Dow products from the standpoint of human health and
applications since 1938. Years of experience in solving environmental quality to ensure that Dow products are not
application needs and developing new products that It is also highly desirable to control dusts in order to prevent used in ways for which they are not intended or tested.
optimize desired performance are available to Dow accidents caused by slippery floors and equipment. As a USP Dow personnel are available to answer your questions and
customers and prospects. grade item, Premium METHOCEL™ cellulose ethers should to provide reasonable technical support. Dow product
not be stored next to peroxides or other oxidizing agents, literature, including safety data sheets, should be consulted
While dusts from METHOCEL™ products could conceivably poisons, pesticides, or ill-smelling articles. prior to use of Dow products. Current safety data sheets are
cause temporary mechanical irritation to the skin and eyes available from Dow.
under extreme conditions, and may be considered as a Accidental Spills
nuisance when breathed, the products are not expected to To prevent employee falls and accidents, floor spills of
present a significant health hazard in handling. Although no dry powder should be thoroughly vacuumed or swept up.
special precautions typically need to be observed to handle Any slight residual product on the walls or floor can then
the products safely, the use of an approved dust respirator in be flushed with water into a sewer. If the spill is a viscous
dusty atmospheres is advised. solution it should be further diluted with water before
disposal.
METHOCEL™ products are organic polymers that will burn
under the right conditions of heat and oxygen supply. Fires
can be extinguished by conventional means.

17  Tablet Coating ®TMTrademark of The Dow Chemical Company (“Dow”) or an affiliated company of Dow Tablet Coating  18
Tablet
Coating

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®TMTrademark of The Dow Chemical Company (“Dow”) or an affiliated company of Dow • Form No. 198-02260 - 10/11 EST

NOTICE: No freedom from infringement of any patent owned by Dow or others is to be inferred. Because use conditions and applicable laws may differ from one location to
another and may change with time, Customer is responsible for determining whether products and the information in this document are appropriate for Customer’s use and for
ensuring that Customer’s workplace and disposal practices are in compliance with applicable laws and other government enactments. The product shown in this literature may
not be available for sale and/or available in all geographies where Dow is represented. The claims made may not have been approved for use in all countries. Dow assumes no
obligation or liability for the information in this document. References to “Dow” or the “Company” mean the Dow legal entity selling the products to Customer unless otherwise
expressly noted. NO WARRANTIES ARE GIVEN; ALL IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE ARE EXPRESSLY EXCLUDED.