Hypromellose USP

PHARMACOAT
R

Film Coating Material and Binder

CONTENTS

Introduction ………………………………………………………………… 2
Description ………………………………………………………………… 3
Physicochemical Properties ……………………………………… 4 ∼ 7
Related Products ………………………………………………………… 8
Applications ………………………………………………………… 9 ∼ 12
Product Specifications ………………………………………………… 13
Precautions for Safe Handling ……………………………………… 14

--- 1 ---
Introduction

Film coating was developed as undercoating for sugar

coating in the 1950's and film-coated tablets were eventually
introduced early in the 1970's. Since then, much development
work aimed at increasing the production rate of film-coated
tablets and reducing the cost has been done in order to
improve the efficiency of pharmaceutical manufacturing, as
well as the bioavailability of drugs, and film coating is now a
well-established and effective technique.
Shin-Etsu Chemical's PHARMACOAT ® was developed from
hydroxypropyl methylcellulose in 1963, during the early days
of film coating, and has been the subject of a continuous
program of development and quality improvement since then.
Film coatings of this type are now in widespread use
throughout the world.
Although drug properties are the key factor in medicinal
formulations, the physical form or the finish of a preparation
is also important. PHARMACOAT® is easy to use as a film
coating material and gives an excellent finish. It is very
versatile, and is suitable for many applications in the design
of film-coated tablet formulations.
In addition, PHARMACOAT® is effective as a binder, since it
does not interact with drugs, and has superior stability,
nonionic character, etc. PHARMACOAT® is widely used as a
binder for granulation, and is available in various viscosity
grades for granulation purposes.
Shin-Etsu Chemical's PHARMACOAT® can make a valuable
contribution in various areas of pharmaceutical technology.
Detail technical information is available in a separate
publication, "Technical Information".

--- 2 ---
 Description

Trade name PHARMACOAT®

Generic name Hypromellose

(Hydroxypropylmethylcellulose)

Abbreviation HPMC

IUPAC name Cellulose, 2-hydroxypropyl methyl ether

CAS registry number 9004-65-3

Compendial status USP (The United States Pharmacopeia)

(As of December 2007) EP (European Pharmacopoeia)
JP (Japanese Pharmacopoeia)

Structure

OR CH2OR
O
O
OR
OR
O
O
CH2OR OR
n

R = -H
-CH3
-CH2CH
（CH3）OH

--- 3 ---
 Physicochemical Properties

1）True density …………… 1.26 - 1.31 g/cm3 (measured with helium pycnometer)

2）Tapped density ……… 0.50 - 0.70 g/mL

3）Equilibrium moisture content …………

  The relationship between relative humidity and equilibrium moisture content of PHARMACOAT ®, PVP and HPC is
shown in Fig. 1. There is no difference in equilibrium moisture content between PHARMACOAT ® and HPC.

4）Permeability of moisture …………

  The relationship between relative humidity and permeability of moisture is shown in Fig 2.

Fig. 1 : Relative humidity and equilibrium moisture content at 25℃ Fig. 2 : Relative humidity and permeability of moisture

40 1200
Permeability of moisture（g/m2・d）

1000
Equilibrium moisture content (%)

30

800

PVP 40℃

20 600

HPC 400

10 25℃

200

PHARMACOAT 606

0
0 10 20 30 40 50 60 70 80 90 100 0 20 40 60 80 100
Relative humidity (%) Relative humidity (%)
Lyssy's method
(Lyssy L80-5000 Water Vapor Permeability Tester)
0.1mm thickness
There is no difference among the grades of PHARMACOAT® There is no difference among the grades of PHARMACOAT®

5）Molecular weight

Grade Mw Mw/Mn
PHARMACOAT 603 16,000 2.00
PHARMACOAT 645 22,000 1.83
PHARMACOAT 606 35,600 1.62
PHARMACOAT 615 60,000 1.89
Mw : weight-average molecular weight (g/mol) Mn : number-average molecular weight

--- 4 ---
 Physicochemical Properties

6）Viscosity behavior Fig. 3 : Concentration-viscosity relationship of

®
PHARMACOAT
5000
a）Viscosity of aqueous solutions 4000
20℃
The relationship between concentration and viscosity of 3000

2000 40℃
PHARMACOAT 603, 645, 606 and 615 in water at 20℃ 20℃
615
and 40℃ is shown in Fig. 3.
1000 40℃
The viscosity grade and the concentration used should be 800
600
606
20℃
selected depending on the required usage. For film 500
400
coating, concentrations reaching 80 − 100 mPa・s are 300 40℃

optimum. For use as a binder, a low viscosity grade is 200

645

︵ mPa･s
︶
effective.
100 20℃
80
60 40℃
50

Viscosity
40
30 603
20

10
8
6
5
4
3

1
0 2 4 6 8 10 12 14 16
concentration（Wt.%）
b）Viscosity of organic solvent solutions
Fig. 5 : Relationship of the mixing ratio in the water/ethanol system
PHARMACOAT is soluble in aqueous alcohols such as
®
and the viscosity of 6% solutions of PHARMACOAT®
1000
ethanol and isopropanol containing water in a ratio more
800
than 10 % water, but insoluble in simple alcohols. Therefore
600
the mixture of water and ethanol is recommendable with
500
the ratio of 20 % water and 80 % ethanol. Solubility in the 615
400
mixture of water and ethanol can be seen in Fig. 4. Fig. 5
300
and Fig. 6 show the viscosities in the water / ethanol
system. 200

When complete organic solvent is required, the mixture of

︵ mPa･s
︶

methylene chloride and alcohol is usable. Fig. 7 and Fig. 8

606
show the viscosities in the methylene chloride / ethanol 100

system. 80
Viscosity

60
645
50

40

30
Fig. 4 : Solubility os Pharmacoat® in ethanol and water
603

20

Ethanol 100 wt% 80 60 40 20 0

Water 0 wt% 20 40 60 80 100
10
Insoluble Soluble but opaque Soluble and transparent 0 10 20 30 40 50 60 70 80 90 100
C2H5OH（Wt.%）
100 90 80 70 60 50 40 30 20 10 0
H2O（Wt.%）

--- 5 ---
 Fig. 6 : Concentration - viscosity relationship of PHARMACOAT® Fig. 7 : Relationship of the mixing ratio in the methylene
in water/ethanol (50:50) chloride/ethanol system and the viscosity of 10%
solutions of PHARMACOAT®
5000 10000
4000
20℃ 8000
3000
615 615
6000
2000
40℃ 606 5000
20℃ 4000
1000
800 3000
20℃ 645
600
500 40℃
2000
400 20℃
300 40℃
603 606
200

︵ mPa･s
︶
1000
40℃
800
︵ mPa･s
︶

100
80 600
645

Viscosity
60 500
50
400
Viscosity

40
30 300
20 603
200

10
8
6 100
5
4 80
3
60
2 50
40
1 30
0 2 4 6 8 10 12 14 16 0 10 20 30 40 50 60 70 80 90 100
concentration（Wt.%） CH2Cl2（Wt.%）
100 90 80 70 60 50 40 30 20 10 0

Fig. 8 : Concentration - viscosity relationship of PHARMACOAT®

C2H5OH（Wt.%）
in methylene chloride/ethanol (50:50)
5000
4000 20℃
3000
606
30℃
2000 20℃ 645
30℃
615 20℃

1000 30℃
800
600 20℃
500
400 30℃
300
603
200
︵ mPa･s
︶

100
80
60
50
Viscosity

40
30

20

10
8
6
5
4
3

1
0 2 4 6 8 10 12 14 16
concentration（Wt.%）

--- 6 ---
 Physicochemical Properties

7）Film properties Fig. 9 : The effect of TiO2 on the tensile strength of

PHARMACOAT® films
®
PHARMACOAT film has the tough and flexible 70
characteristics of cellulose derivatives. Although
PHARMACOAT® film is not brittle, as acrylic polymer is,
60
addition of a plasticizer such as polyethylene glycol (PEG 615

6000) is effective when highly flexible film is required.

606
When PHARMACOAT ® film is used for film coating, 50

Tensile strength (MPa)

sometimes titanium dioxide (TiO2) or talc is recommended
to be added. Fig. 9 and Fig. 10 show the properties of
40
PHARMACOAT® film containing TiO2. For the experiment, 645

film with a thickness of 0.1 mm, which was obtained by

dissolving PHARMACOAT® in methylene chloride/ethanol 30

mixture (50 : 50), adding TiO2 to the solution and casting it

603
on a glass plate, was used. The measurements were
20
performed under the conditions of 25 ±1℃ , 50±5%RH PHARMACOAT 603 film loaded with
higher than 20 % of TiO2 could not be
obtained due to its brittleness
according to JIS K-6301.
Addition of inorganic substance such as TiO2 in a large 10
0 10 20 30 40 50 60
amount to a grade of PHARMACOAT 603 with low TiO2 content to PHARMACOAT® (%)
viscosity (molecular weight) causes a marked decrease in
the tensile strength, often leading to cracking and/or
Fig. 10 : The effect of TiO2 on the elongation of
peeling of the films. Therefore, when an inorganic PHARMACOAT® films
substance is added, use of a grade with a relatively high
viscosity (molecular weight) such as PHARMACOAT 645,
606 or 615 is recommended. 20

Moreover, addition of a water-insoluble polymer such as

Hypromellose Phthalate (HPMCP) to PHARMACOAT ®
delays dissolution of the film, which is useful for the 15
masking of bitter taste or unacceptable texture, as well as
Elongation (%)

delaying drug dissolution. Table 1 shows the solubility of

such a mixed film in simulated gastric fluid and simulated 10
intestinal fluid. The test piece had a thickness of 0.08 mm
and size of 10 mm × 10 mm. For the test, the apparatus 615
for the USP Disintegration Test was used. Hypromellose
5
Phthalate (HPMCP) used in this study is HP-50. 606

603 645
Table 1 : Solubility of the films in pH 1.2 and 6.8 buffer solutions 0
0 10 20 30 40 50 60
Mixed film Mixing ratio Simulated gastric fluid Simulated intestinal fluid
TiO2 content to PHARMACOAT® (%)
9／1 Soluble Soluble
8／2 Soluble Soluble

PHARMACOAT 606/ 7／3 Soluble Soluble

HPMCP 6／4 Low Soluble
5／5 Nearly insoluble Soluble
4／6 Nearly insoluble Soluble
3／7 Nearly insoluble Soluble

--- 7 ---
 TC-5® の関連商品

Related Products

Regular types of Hypromellose (hydroxypropyl
methylcellulose) or Methylcellulose are commercialized
under trade name of METOLOSE ®, which are used as
binders for solid dosage forms, thickening agent for liquid
preparations and sustained release matrix agent.
SB-4 is used as a binder for sugar coating instead of gelatin
and gum Arabic. Data on these products will be provided
on request.

Table 2 : Outline of types of Hypromellose (hydroxypropyl methylcellulose) or Methylcellulose

Labeled viscosity*1 Hypromellose Hypromellose Hypromellose

Methylcellulose
(mPa・s) Substitution type: 2208 Substitution type: 2906 Substitution type: 2910

3 PHARMACOAT 603

4 SB-4 METOLOSE SM-4

4.5 PHARMACOAT 645

6 PHARMACOAT 606

15 PHARMACOAT 615 SM-15

25 SM-25

50 METOLOSE 65SH-50 METOLOSE 60SH-50

100 90SH-100SR SM-100

400 65SH-400 SM-400

1500 65SH-1500 SM-1500

90SH-4000
4000 65SH-4000 60SH-4000 SM-4000
90SH-4000SR

10000 60SH-10000

90SH-15000
15000
90SH-15000SR

90SH-100000
100000
90SH-100000SR

Substituent content
19.0 - 24.0 %*2 27.0 - 30.0 % 28.0 - 30.0 % 26.0 - 33.0 %
Methoxy group
4.0 - 12.0 %*2 4.0 - 7.5 % 7.0 - 12.0 % −
Hydroxypropoxy group

*1 The viscosity is measured with 2 wt % aqueous solution at 20 ºC.

*2 METOLOSE ® SR products have tighter specification ranges.

Application Guide for PHARMACOAT ®

Application Purpose

Film coating for tablet Taste masking, Color masking, Coloring, Hardness (improve friability),
Stability

Sub-coating for sugar coating Stability, Prevention of moisture penetration to the core

Sub-coating for enteric coating Prevention of interaction

Binder for tablet and granule Compressibility, Compatibility

--- 8 ---
 Applications
1）Technique for dissolving PHARMACOAT®
®
As PHARMACOAT is a powder with particle size of 50 -
70 μm, dissolution of a large amount of PHARMACOAT®
must be done carefully to avoid loss of material through
dust formation (dusting). Moreover, as PHARMACOAT®
has high solubility in water and mixed solvents, it may form
lumps, which require a long time to dissolve, if it is added to
such solvents all at once. Therefore, PHARMACOAT
should be dissolved according to the following procedures.
a）Dissolving in water
Put all of the PHARMACOAT® in about 1/3 of the water,
previously heated to above 80℃ , while stirring well at
higher speed. Because hot water is a poor solvent for
®
PHARMACOAT , a uniformly wet dispersion is obtained.
Then, add cold water to make the prescribed volume while
stirring well. After cold water is added, slow down the
stirring speed to lower speed and continue until the
®
PHARMACOAT disssolves completely. When the
t e m p e r a t u r e o f t h e w a t e r f a l l s t o b e l o w 30 ℃ ,
PHARMACOAT® can dissolve completely and the solution
can be used as a coating fluid. If a high-power stirrer is
used, PHARMACOAT® can be readily dissolved by adding
it gradually to the water at below 30℃ with stirring. Care
must be taken to avoid bubble or foam formation.
At 6 - 10 % viscosity (less than 100 mPa・s) any bubbles
formed disappear when the solution is left to stand for
several hours. The following can be employed as antifoaming
agents : Shin-Etsu Silicone KM-72 (Polydimethylsiloxane)
from Shin-Etsu Chemical / NIKKOL SO-15 (Sorbitan
sesquioleate) from Nikko Chemicals / Pulronic F 68
(Polyoxyethlene(160)-polyoxypropylene(30)glycol) from Asahi
Denka.
b）Dissolving in organic solvents
(water / ethanol system)
As PHARMACOAT® is insoluble in simple alcohols, first of
all pour a prescribed volume of ethanol into a container and
put all of the PHARMACOAT® in it while stirring. When a
uniform dispersion is obtained, add water gradually and
stir gently to form a well-wetted dispersion as the coating
solution. If PHARMACOAT ® is put all at once into a
previously prepared mixed solution, insoluble lumps will be
formed.
Although great care is taken to avoid any foreign material
contamination, it is recommended to sieve the product
and/or filter the product solution before usage.
*If difficulties arise concerning the dissolution apparatus,
removal of bubbles in the coating solution or filtration of
solutions, Shin-Etsu can offer technical advice based on
® extensive experience and know-how.
2）Film coating
Film coating is usually done with aqueous solutions rather
than organic solvents, since the cost of the solvent is less,
the cost of equipment is less (solvent recovery and disposal
are simpler), and the process is safer (better working
environment, less risk of explosion and no need for
treatment to remove residual solvents in preparations).
Accordingly, Shin-Etsu recommends the adoption of coating
with an aqueous solution. Machinery which offers a high
drying efficiency and short coating time is available. Some
examples of coating using PHARMACOAT® are given in
Table 3. In addition to those illustrated many coatings
available for particular purposes such as improving abrasion
resistance, improving printability, improving impact
strength, masking color and/or taste, and improving
flowability. Coating formulation and quantities differ
considerably depending on the purpose, and it is necessary
to change the formulation of the coating solution, the drying
temperature and the operating parameters of the coating
equipment on a case-by-case basis. Shin-Etsu Chemical can
provide technical advice on the suitability of various
coatings.
--- 9 ---
Table 3 : Examples of film coating with PHARMACOAT®

1）Example of coating using organic solution 2）Example of coating using auqeous solution
Laboratory scale apparatus Laboratory scale apparatus
a）Composition of coating solution a）Composition of coating solution
 PHARMACOAT 606 ………………………………………………… 8 parts 606 645
 Ethanol ……………………………………………………………… 75.2 parts  PHARMACOAT 6 parts 10 parts
 Water ……………………………………………………………… 18.8 parts  Water 94 parts 90 parts
b）Coating conditions b）Coating conditions
 Apparatus ………… New Hi-Coater HCT-48N (Freund corporation)  Apparatus   New Hi-Coater HCT-48N (Freund corporation)
 Dimension …………………………………………………………… 480 mm  Dimension         480 mm
 Pan speed ………………………………… 16 (20 at later atage) min-1  Pan speed         16 min-1
 Spray gun … air spray gun × 1 (AT type nozzle diameter 1.2 mm)  Spray gun air spray gun X 1 (AFT type nozzle diameter 1.2 mm)
 Drying air …………………………………………………………… 55 ∼ 60℃  Drying air 70℃ ←
 Air flow rate …………………………………………………………3 m3/min.  Air flow rate 2.5 m3/min ←
 Spray speed ……………………………………………………… 40 g/min.  Spray speed 20 g/min ←
 Nozzle air ………………………………………………………… 120 L/min.  Nozzle air 150 L/min ←
 Pressure of spray air ……………………………………………… 350 kPa  Pressure of spray air 200 kPa ←
 Tablet bed air temperature …………………………………… 46 - 39 ℃  Tablet bed temperature 39℃ ←
 Charge per batch …………………………………………………………………  Charge per batch 5 kg ←
25,000 tablets, 5 kg (dosage form; 8 mm, 200 mg/tab.)  Dosage form 6.5 mm, 120 mg/T ←
c）Results c）Results
 Coating time …………………………………………………………62.5 min.  Coating time (3% coating based on tablet weight)
 Coating solution consumption ………………………………… 2500 g   83 min  50 min
 PHARMACOAT 606 consumption ………………………… 6mg/Tab.  Coating solution consumption 2490 g 1500 g
 Disintegration time (USP disintegration test, average) ………………  PHARMACOAT 606 consumption
before cooaing; 2 min 20 sec. 3.6 mg/tab. ←
  after coating; 3 min 30 sec. Disintegration time (USP disintegration test, average)
before coating: 2 min 20 sec ←
Production scale apparatus after coating: 3 min 30 sec ←
a）Composition of coating solution
 PHARMACOAT 606 ………………………………………………… 6 parts Production scale apparatus
 Ethanol ……………………………………………………………… 75.2 parts a）Composition of coating solution
 Water ……………………………………………………………… 18.8 parts 606 645
b）Coating conditions  PHARMACOAT 6 parts 10 parts
 Apparatus ……… New Hi-Coater HCT-130N (Freund corporation)  Water 94 parts 90 parts
 Dimension ………………………………………………………… 1300 mm b）Coating conditions
 Pan speed ……………………………………… 5 (8 at later atage) min-1  Apparatus  New Hi-Coater HC-130N (Freund corporation)
 Spray gun … air spray gun × 3 (AT type nozzle diameter 1.2 mm)  Dimension 1300 mm
 Drying air …………………………………………………………… 50 ∼ 60℃  Pan speed 8 min-1
3
 Air flow rate ……………………………………………… 10 ∼ 15 m /min.  Spray gun  air spray gun X 3 (AT type nozzle diameter 1.2 mm)
 Spray speed ………………………………………………… 140 g/min.×3  Drying air 80℃ ←
 Nozzle air ………………………………………………… 140 ∼ 150 L/min.  Air flow rate 15 m3/min ←
 Pressure of spray air ……………………………………………… 400 kPa  Spray speed 80 g/min×3 ←
 Tablet bed air temperature …………………………………… 37 - 30 ℃  Nozzle air 170 L/min ←
 Charge per batch …………………………………………………………………  Nozzle air + pattern air 250 L/min ←
600,000 Tablets, 120 ㎏ (dosage form; 8 mm, 200 mg/tab.)  Tablet bed temperature 46℃ ←
c）Results  Charge per batch 120 kg ←
 Coating time ………………………………………………………… 143 min.  Dosage form 6.5 mm, 120 mg/T ←
 Coating solution consumption ………………………………… 60.0 kg c）Results
 PHARMACOAT 606 consumption ………………………… 6 mg/Tab. Coating time (3% coating based on tablet weight)
 Disintegration time (USP disintegration test, average) ………………  286 min 171 min
before cooaing; 2 min 20 sec. Coating solution consumption 60.0 kg 35.9 kg
after coating; 3 min 30 sec. PHARMACOAT 606 consumption
3.6 mg/tab. ←
Disintegration time (USP disintegration test, average)
before coating: 2 min 35 sec ←
after coating: 3 min 40 sec ←

--- 10 ---
 Applications

3）Dissolution characteristics of Fig. 12: The results of dissolution tests of coated tablets at
various pH values
PHARMACOAT® - coated tablets
dissolution medium : water
The coated tablets must release the drug in simulated gastric
100
fluid. Moreover, it is essential that the drug is dissolved in
water and buffer solutions with various salt concentrations
80
and pH values similar to those of simulated gastric fluid.
This is because the pH value of human gastric juice shows

% released
60
inter-individual variation depending on age, constitution, etc.,
and the drug therapeutic effect is required to be maintained 40
irrespective of such differences. PHARMACOAT® film has
very favorable dissolution characteristics from this point of 20
acrylic polymer 0 %
view, and this is one of the main reasons why
vinyl polymer 0 %
PHARMACOAT® is widely used as a coating agent.
0 3 6 9 12 15 18 21
To illustrate the superior dissolving characteristics, 190 mg
Time (min)
vitamin B2 tablets containing 3.2 mg of vitamin B2 were
coated with various agents and their dissolution characteristics
were compared. Fig. 11 and Fig. 12 show the results. dissolution medium : simulated gastric fluid

In the case of agents having pH-dependent dissolution 100

characteristics such as acrylic polymer and polyvinyl

polymer, water-soluble polymers or other additives may be 80

required, but PHARMACOAT® has uniform dissolution

% released

60
characteristics, making it easy to use.

40
Symbols in Fig.11 and Fig.12:
Core tablet Coated with acrylic polymer
20
Coated with PHARMACOAT® Coated with vinyl polymer

Coated with HPC

0 3 6 9 12 15 18 21
Time (min)
Fig. 11: The 70% dissolutioin time of tablets coated
with various coating materials
no dissolution after 60 min
dissolution medium : pH 6.0 (Clark-Lubs)

100
10 28'57"
70% dissolution time (min)

80
8
% released

60
6

40
4

2 20

vinyl polymer : 0 %
0
simulated 1.2 2.0 4.0 6.0 water 0 3 6 9 12 15 18 21 24 27 30
gastric fluid
Clark-Lubs buffer solution Time (min)

--- 11 ---
4）Granulation
®
PHARMACOAT can also be used as a binder for granulation.
The fine particle size (average 50 - 70μm) allows good
admixture with the vehicle (lactose/cornstarch) and
PHARMACOAT® is effective for fluidized bed granulation
and high shear mixer granulation (dry-blend).
Although the details are not given here, a low viscosity grade
(typically PHARMACOAT 603) is more effective as a binder
for granulation, which can afford the powders with good
compressibility. Shin-Etsu recommends the use of
®
PHARMACOAT for fine granules and tabletting granules as a
highly stable binder which does not interact with active substances.

Table 4: Formulation Table 6: Properties of granules

Wet granulation Fluidized bed High shear mixier Fluidized bed

Granulation method
Dry form Solution Dry form Solution Dry form Solution Dry form Solution

Lactose Binder content 3％ 1％ 5％ 3.5 ％

(DFE Pharma 200 mesh) 3360 g 3360 g 2800 g 2800 g
Mean particle size（μm） 223 203 211 220

Cornstarch 1440 g 1440 g 1200 g 1200 g Loose 0.635 0.621 0.534 0.450
Bulk density
MCC （g/mL） Tapped
200 g 200 g − − 0.789 0.785 0.612 0.553

PHARMACOAT 606 150 g 50 g* 200 g 140 g* Angle of repose （゜ ） 37 37 35 34

Granulating liquid (water) 1000 g 1000 g 1600 g 1860 g Moisture content（％） 2.2 2.6 3.2 2.6
*Dissolved in granulating liquid

Fig. 13: Cumulative particle size distribution

Table 5: Conditions (high shear mixer)
0
Dry mixing Solution
Vertical granulator FM-VG-25
Machine
Granulation

(Powrex Corp.)

Granulating time 10 min

Blade 300 min-1

Oversize (%)

Chopper 3000 min-1

Machine Flow coater FLO-5 (Freund Corp.)

50
Drying

Drying temperature 70 ℃

Air flow 2.2 m3/min

Drying time 30 min

Conditions (fluidized bed)

Dry mixing Solution
100
Machine Flow coater FLO-5 (Freund Corp.) 50 100 200 500 1000 2000

Drying air temperature 82-83 ℃ 83-84 ℃ SIZE（micron）

Exhaust air temperature 28-30 ℃ 29-32 ℃ High shear mixer with dry form
Granulation

Air flow 2.2 m3/min 40 m3/min High shear mixer with solution
Spray gun Schlick nozzle 1.8 mm Fluidized bed with dry form

Spray air pressure 300 kPa Fluidized bed with solution

Gun position 25 cm 40 cm
Spraying time 25 min 20 min
Shaking/interval 6 sec/30 sec

End point When the outlet temperature came to 35℃

Drying air temperature The same as at granulation condition

Drying

Air flow 2.2 m3/min

Shaking/interval 6 sec/180 sec

Drying time 15 min 7 min

--- 12 ---
 Products Specifications

PHARMACOAT® meets all the requirement for the USP
Hypromellose (Substitution type: 2910), EP Hypromellose
and JP Hypromellose. Moreover, in addition to the tests
prescribed in the aforementioned Pharmacopeias, Shin-Etsu
carries out tests for foreign matter contamination,
microbiological contamination, yellowness index, etc., in
order to ensure strict quality control. PHARMACOAT® in
manufactured in accordance with the good manufacturing
practice (self-GMP). A certificate of analysis commonly
incorporating test results on the USP, are routinely attached
to PHARMACOAT® products. Quality specifications are
shown in the following table.

Table 7 : Specifications of PHARMACOAT ®

Grade 603 645 606 615

Method
Substitution type 2910

Apperance White to slightly off-white powder Visual

Characters Conforms EP

Identification A∼Ｅ Conforms USP

Appearance of solution Conforms EP

Viscosity 2.4∼3.6 mPa・s 3.6∼5.1 mPa・s 4.8∼7.2 mPa・s 12.0∼18.0 mPa・s USP

pH 5.0∼8.0 USP

Heavy metals Not more than 20 ppm USP

Loss on drying 5.0 % Max. USP

Residue on ignition 1.5 % Max. USP

Methoxy content 28.0∼30.0 ％ USP

Hydroxypropoxy content 7.0∼12.0 ％ USP

SB-4(Hypromellose 2208) is especially useful as a binder for sugar coating, which is an alternative source of gelatin and gum
Arabic in sugar coating syrup. Please contact us for further information. Specification of SB-4 is available on request.

N O T E :
All the information and data in this brochure are accurate and reliable to the best of our knowledge, but they are intended only to
provide recommendations or suggestions without guarantee or warranty. All of our products are sold on the understanding that
buyers themselves will test our products to determine their suitability for particular applications. Buyers should also ensure that use
of any product according to these data, recommendations, or suggestions does not infringe any patent, as Shin-Etsu will not accept
liability for such infringement. Any warranty of merchantability or fitness for a particular purpose is hereby disclaimed.

--- 13 ---
 Precautions for Safe Handling
Warning: May form flammable or
Explosive dust-air mixtures.
When handling, avoid accumulation and suspension of
dust in the air.
Store away from heat sources, sparks, and flame. Do
not permit grinding, welding, or smoking near this
material.
General precautions outlined in the National Fire
Protection Association's NFPA654 "Standard for the
Prevention of Fire and Dust Explosions from the
Manufacturing, Processing, and Handling of Combustible
Particulate Solids" and NFPA 77 "Recommended Practice
on Static Electricity" are recommended.
(Minimum Explosive Concentration: 55 g/m3, Mukai et al.,
1995)
CAUTION: Spilled powder becomes slippery
when wet. May cause eye irritation.
Avoid contact with eyes, skin and clothing.
Wash thoroughly after handling.
Wash contaminated clothing before re-use.
Use only with adequate exhaust ventilation.
Follow and organized house keeping plan.
Keep floors and equipment clean.
Emergency and first aid procedures
If inhaled: Remove to fresh air. Give artificial
respiration if breathing stops. Get immediate medical
attention.
In case of eye contact: Flush eyes with plenty of fresh
water while holding eyelids open. Get immediate
medical attention.
In case of skin contact: Wash off with flowing water.
Package
● 50kg - Fiber drum with polyethylene double bag
inside
● 1kg - Polyethylene double bag
--- 14 ---
In case of material spills and leakages
The following steps should be taken.
- Wear an approved respirator, rubber gloves, rubber
boots and safety goggles.
- Vacuum or sweep up spillage.
Prevent dustgeneration. Place spillage in an appropriate
container for waste disposal.
- Ventilate area and wash spill site.
- Wash contaminated clothing before reuse.
- If spillage is viscous solution, scrape up as much as
possible before flushing it with plenty of water.
Place the scraped spillage in an appropriate container
for waste disposal.
Storage
Keep dry. Store away from excess heat and sunlight.
Store in sealed containers.
Disposal
Contents: Dispose of unused contents in accordance
with all applicable federal, state and local laws.
Consult the distributor for further information.
Container: Do not re-use container. Dispose of empty
container by incineration or the procedures approved
by federal, state and local authorities.
***********************************************************
Carefully read and understand the safety data sheet
(SDS) before this product.
 Shin-Etsu Chemical Co.,Ltd

Cellulose & Pharmaceutical Excipients Department

6-1, Ohtemachi 2-chome, Chiyoda-ku, Tokyo, 100-0004
Japan
TEL: 81-3-3246-5261 FAX: 81-3-3246-5372
http://www.metolose.jp/e

2014.9/1000