Dow Pharma & Food Solutions

ETHOCEL High Productivity (HP)

Safe. Fast. Efficient.

ETHOCEL HP

Improving Productivity Through Innovation

As our oldest brand, Dow continues to invest in and innovate
with ETHOCEL. Our constant pursuit of production excellence
has helped us out manufacture our competition by producing
ethylcellulose (EC) that is less fibrous, narrower in viscosity,
and tighter in ethoxyl functionality than other ethylcellulose
producers. And now, weve optimized our ETHOCEL offering
for a new dry powder layering process using rotor technology.
This rotor technology allows customers to coat multiparticulates, powders, even mini-tablets without the need
for solvent or aqueous-based polymer systems. Just enough
moisture is added to allow adherence of the polymer to
the substrate but the barrier membrane polymer is added
completely as a dry powder.
Our tailored ETHOCEL offering is ideal for this new coating
technology. Trials show that using our innovative ETHOCEL HP
(High Productivity) product in a rotor coater allows for improved
productivity and shorter coating times, while completely
eliminating the need for environmentally-harmful solvents.
This new technology can be a powerful solution for our
customers looking to move away from solvent-based systems,
without experiencing the long coating time and potential
stability issues of aqueous-based dispersions.

Figure 1. VFC-LAB 3 FLO-COATER with GXR-35 Rotor Insert.

By using ETHOCEL HP, your formulation can remain simple

and robust, avoiding concerns around tackiness and stability
often found with low Tg polymers such as methacrylate based
technology which requires not only significant amounts of talc
for the dry powder layering process and post processing coating,
but also additives overall to avoid agglomeration. Customers
looking for innovative solutions to their formulation challenges
can turn to our latest ETHOCEL HP product combined with
this rotor technology to provide alternative solutions in the
areas of controlled release and taste masking.
Through our CR Alliance with Colorcon, we offer this new
product with the backing of the application expertise our
partners bring to the industry. We have also collaborated with
Freund-Vector in the development of this product, as their
equipment knowledge has proven invaluable in ensuring our
new polymer offering brings the right productivity benefits to
our customers while processing cleanly.

Why Go With This Solvent-Less System?

ETHOCEL HP can help you:
Coat 40-60% faster than current MUPS coating technologies
Achieve 98 - 99% coating efficiency consistently
Improve sustainability (with the elimination of solvents)
Avoid high solvent costs including costs of disposal,
capital expenditure, and infrastructure modifications
Improve operational safety

Figure 2. GRANUREX GXR-35 Rotor.

ETHOCEL HP

Atomization of
Solution

Layer Formation

Final Film
Formation

Process repeated thousands of

times to form uniform film

ETHOCEL in organic solvent

or as aqueous dispersion
sprayed onto substrate

Droplet spreading
and evaporation

ETHOCEL Layer
Formed

Final Film
Formation

Figure 3. The spray coating process.

Figure 4. Cross sectional image (left) and magnified view (right) of ETHOCEL barrier membrane
formed from solvent solution.
Initial wetting and
powder feeding

Rotor Layering
(rolling snowball effect)

Final Film
Formation

Curing to induce
coalesence

ETHOCEL HP
Tacking Agent:
Water & Plasticizer

Repeated liquid and

solid bridging

Figure 5. The dry powder layer process.

How The Spray Coating Process Works

Typical spray coating systems of ethylcellulose rely on a
dissolving the polymer in a solvent or dispersing in an
aqueous medium to apply the coating onto the substrate. Film
formation process occurs by atomizing the solution into small
droplets that pelt the surface of the substrate at which point
the carrier medium (solvent or water) is quickly evaporated
and the ethylcellulose remains on the surface of the substrate.
This process is repeated thousands of times during the coating
process, resulting in many layers of ethylcellulose that deposit
on the surface of the substrate and coalescence into a solid,
homogenous film. The industry understands this system,
which allows for great film-formation, and is compatible with
both aqueous and solvent systems. Solvent-based coatings
provide stable, reproducible coatings but the use of solvents
can be problematic for customers who dont have solvent
capabilities at their sites.

How The Dry Powder Layering Process Works

The dry powder layering process applies the coating from a
dry state onto a substrate by first wetting the substrate with
a tacking agent such as a plasticizer/water combination. After
sufficient wetting, the dry polymer powder is applied to the
wet surface of the substrate upon which liquid bridging occurs
between the dry powder particles and the surface of the
substrate. The presence of the plasticizer lowers the Tg of the
polymer to levels for proper film formation. The wetting agent
and dry powder are continually sprayed on to the substrates
and polymer layers are formed similar to a snow ball forming
as it rolls down a hill due to the unique rotor insert design
and small gap for slit air flow. After sufficient coating, the dry
powder coated substrates are cured and stored. This dry process
reduces all environmental concerns faced with solvent systems.
It greatly improves efficiency as well, as the powder that goes
into the system finds itself on the substrate surface, and there
is no solvent or minimal liquid that needs to be driven off in
the process. The unit allows for flexibility in processing, where
one could perform API-layering, followed by a coating step, and
finished with a curing step all in the same piece of equipment.
Overall, processing is much faster.

Figure 6. Cross sectional image (left) and magnified view (right) of ETHOCEL HP barrier membrane
formed from dry powder rotary coating process.

ETHOCEL HP

How Does ETHOCEL HP Work In This Process?

ETHOCEL HP was specifically designed to be most efficient in a
dry powder coating setting. The mean particle size and particle
size distribution has been optimzed for best controlled release
performance.
These case studies demonstrate product attribute effects and
improvements over standard manufacturing technologies in
enhanced productivity, decreased coating times, and better
environmental impacts by removing solvent use.

Table 1. Particle size specification (in microns).

Particle size
specification

ETHOCEL Std

ETHOCEL FP

ETHOCEL HP

D10

N/A

N/A

<3

Mean

N/A

3-15

<8

D90

N/A

N/A

< 15

Maximum

N/A

100

N/A

Since ethylcellulose is applied from the dry state, a curing step is strongly recommended to ensure film stability. Curing can be
done in-situ in the equipment (referred to as dynamic curing) or in tray ovens (static curing).
Table 1 shows how we have tightened our particle size distribution to allow for best performance in a dry form. Considering
coating thickness can range from 40 - 100 microns, one can imagine how just one larger particle can harm the integrity of the
overall coating hence the importance of narrowing the particle size distribution.

Fast Coating Times and Weight Gain Influence

For a 200 kg batch size, Figure 7 illustrates how the dry powder delivery of ETHOCEL HP significantly reduces coating times
compared to aqueous ETHOCEL and organic ETHOCEL even when a 2 hour cure step is included for ETHOCEL HP and aqueous
ETHOCEL. For example, at 20% weight gain, ETHOCEL HP only takes 3.5 hours whereas organic ETHOCEL takes 9.8 hours and
aqueous ETHOCEL 7.2 hours.
Acetaminophen drug release was determined for ETHOCEL HP barrier coatings ranging from 5 - 30% weight gain. 25% dibutyl
sebacate plasticizer was used with respect to ETHOCEL HP weight and dissolved in water. No pore formers were used and samples
were statically cured for 2 hours at 60C. Figure 8 shows how drug release was predictably controlled by incremental weight gain.

16

12

Organic ETHOCEL

80

ETHOCEL HP

%APAP Released

Coating Time (hr)

14

100

Aqueous ETHOCEL

10
8
6

60
40

30% wg

2
10%

20%

Weight Gain
Figure 7. Equivalent performance coating times including curing.

5% wg

20

0%

5% wg
10% wg
15% wg
20% wg
25% wg
30% wg

30%

400

800

1200

1600

Time (min)
Figure 8. Influence of ETHOCEL HP weight gain on Acetaminophen drug release.

ETHOCEL HP

80

IPA/H20: 25/75

Acetaminophen drug release was determined for 20% weight

gain of ETHOCEL HP. 25% triethyl citrate plasticizer was used
with respect to ETHOCEL HP weight and dissolved in varying
concentrations of isopropyl alcohol and water. No pore formers
were used and samples were statically cured for 2 hours at 60C

70

IPA/H20: 75/25

60

IPA/H20: 0/100

Increased solvent provides improved film coalescence, but

solvent-free (purely aqueous) performance is the best (Figure
9). The fast evaporation rates of solvents compared to aqueous
based solutions does not provide enough time for liquid
bridging and particle to particle interaction to successfully form
a complete coalesced film (Figure 10).

%APAP Released

Solvent Influence

50
40
30
20
10
0
0

400

800

Time(min)

1200

1600

Figure 9. Influence of solvent levels on acetaminophen drug release using ETHOCEL HP.

Figures 10. ETHOCEL HP film formation for 25% isopropanol / 75% water (left), 75% isopropanol / 25% water (center), and 0% isopropanol / 100% water (right).

Curing Influence
Due to the nature of the ETHOCEL HP and rotary coating process, a cure step is required to achieve full film coalesence
and assure stability and reproducible performance (Figure 11). The cure step for ETHOCEL HP coated substrates can be done
dynamically or statically. Static curing is defined as taking the ETHOCEL HP coated samples and placing them on a tray and
placing in an oven at a set temperature and time.
Dynamic curing allows the customer to keep the coated samples in the rotor processor and use forced hot air from above plus
the frictional movement of the product bed to induce curing of the film. Dynamic curing can allow customers for true one stop,
one pot, processing conditions where API drug layering, functional coating, and curing can be completed in the same piece
of equipment. Dynamic curing also enduces smooth and uniform film formation on the surface of the substrates coated with
ETHOCEL HP compared to static curing (Figure 12).
Experiments have demonstrated that static and/or dynamic curing can be sufficient for film formation, but deciding which type of
curing and degree of curing (length/time) is formulation dependent.

Figure 11 Cross-sectional images of uncured (left) and cured (right) samples coated with ETHOCEL HP

Figure 12: Surface morphology of static curing (left) and dynamic curing (right)

ETHOCEL HP

Equivalent Performance Of Highly Soluble Drug

The ETHOCEL HP applied at 20% weight gain has equivalent

performance to organic ETHOCEL applied at 10% weight gain
without any lag in drug release in the first 60 minutes (Figure
13). Although a higher amount of ETHOCEL HP was needed
in this example, total coating time only took 221 minutes
including the 2 hour cure step whereas organic ETHOCEL took
293 minutes. More time saving could be achieved by switching
to dynamic curing.

100
90
80
Dissolved (%)

Metoprolol tartrate drug release was determined for 20% weight

gain of ETHOCEL HP. 40% dibutyl sebacate plasticizer was used
with respect to ETHOCEL HP weight and dissolved in water.
No pore formers were used and samples were statically cured
for 2 hours at 60C. Metoprolol tartrate drug release was also
determined for 10% weight gain of ETHOCEL Std 10 Premium
which was dissolved in 90% isopropanol and 10% water. 10%
dibutyl sebacate plasticizer was used with respect to ETHOCEL
Std 10 premium weight and dissolved in the same solution. No
pore formers were used and samples were not cured.

70
60
50
40

ETHOCEL HP - uncured

30

ETHOCEL HP - static cured 60C - 2hrs

20

Organic EC-10%wg

10
0

200

400

600
800
Time(min)

1000

1200

Figure 13. Metoprolol tartrate drug release for ETHOCEL HP

rotary coatings or organic ETHOCEL spray coatings.

Improving Particle Size For Improved Film Formation

Acetaminophen drug release was determined for 20% weight gain for Dow ethylcellulose milled at various mean particle size and
particle size distributions (Figure 14). 25% dibutyl sebacate plasticizer was used with respect to ethylcellulose weight and dissolved
in water. No pore formers were used and all samples were statically cured for 2 hours at 60C. As mean particle size becomes
smaller and particle size distributions are tightened, film formation is improved. Larger mean particle sizes even after curing
resulted in highly porous films, whereas ETHOCEL HP after curing had a fully formed film and slowest drug release.

90

X : 50um

80

%APAP Released

70
60

X : 24um

50

X: 50um

40

X: 5um

30

X : 5um

20

Table 2. Particle size distributions of ethyl cellulose samples.

10
0

400

800
Time (min)

1200

Figure 14. Influence of particle size on film formation and drug release.

X: 24um

1600

Sample

D10 (m)

Mean (m)

D90 (m)

ETHOCEL HP

Medium Size

24

55

Large Size

50

108

ETHOCEL HP

Productivity Modeling Work

400
Days of Production

A case model using Venlafaxine HCl was used to determine

the productivity opportunities that would exist using the
ETHOCEL HP coating process versus the next best alternative
spray coatings. The productivity model evaluated companies
of various sizes including a large company which would
manufacture 400 million dosage units a year, a Medium
company with 100 million dosage units a year, and a Small
company with 30 million dosage units a year. Assumptions
employed included: using once piece of equipment for 24hr 7
days a week, 200 kg batch size, and equivalent performance at
10% weight gain Organic ETHOCEL to 20% weight gain Aqueous
ETHOCEL to 20% weight gain ETHOCEL HP. Processing
parameters and time elements of the model are tabled below.

400 MM Dosage Units

100 MM Dosage Units
30 MM Dosage Units

363

300

266

200

154
91

100
0

67
28

20

Aqueous
ETHOCEL

Organic
ETHOCEL

39

12

ETHOCEL
HP

Figure 15. Number of days of production for aqueous ETHOCEL or organic

ETHOCEL spray coatings and ETHOCEL HP dry powder rotary coatings

Table 3. Coating process batch size.

Coating process

Spray/Powder
Delivery Rate (g/min)

% ETHOCEL In Solution

Cure Time (min)

Additional Steps (pre-heat, solution prep)

ETHOCEL HP

450

100%

120

10

Aqueous ETHOCEL

900

15%

120

90

Organic ETHOCEL

1200

6%

90

ETHOCEL High Productivity is an innovative, new product for

the greater ETHOCEL portfolio which enables customers to
increase productivity while still maintaining the advantages
of Dow manufactured ETHOCEL such as tight viscosity,
narrow ethoxyl distribution, and reduced fiber content. Using
ETHOCEL HP could result in up to 60% reduction in coating
times versus aqueous ETHOCEL and 40% reduction versus
organic ETHOCEL spray coating systems. In addition to
the controlled release market, ETHOCEL HP and the rotor
technology can also be extended to taste masking to eliminate
the bitter taste of actives upon swallowing. Proven to be
most effective as a solvent-less coating, this new technology
enables customers to achieve processes which are sustainable,
environmentally friendly, and safe for their employees.

Amount Manufactured (Kg)

Modeling indicates any company of any size will experience a dramatic decrease in coating time using the ETHOCEL HP product.
Coating times decreased by 60% compared to aqueous systems and 40% compared to organic systems (Figure 15). But what does
that improvement really mean for you? It could yield increased production capability to make more product in a given year, or
free equipment to work on other products as well! For example, using the venlafaxine case study, we can estimate the additional
amount one can manufacture (kg) using the ETHOCEL HP technology in same amount of time it would take to use aqueous
ETHOCEL or organic ETHOCEL spray coatings (Figure 16).
100,000
75,000
50,000
25,000
0

67,600
36,488
ETHOCEL HP vs
Aqueous ETHOCEL

ETHOCEL HP vs
Organic ETHOCEL

Figure 16. Additional manufacturing amounts when switching to ETHOCEL HP

technology vs traditional aqueous ETHOCEL or organic ETHOCEL spray coatings.

Dow-Colorcon Alliance: UNIQUE TOGETHER

Dow Pharma & Food Solutions and Colorcon, together in the Controlled Release
Alliance, bring joint resources in polymer and formulation expertise to accelerate your
pharmaceutical product development efforts and reach markets throughout the world.
Colorcon has exclusive, global sales and distribution rights for Dow products used in
controlled release applications, including ETHOCEL.

Dow Pharma & Food Solutions

www.dowpharmaandfood.com

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