Hypromellose

PHARMACOAT: CONTENTS PAGE 2

Preface 3
Designation and structural formula of PHARMACOAT 4
Designation, Admissions to compendia,
Chemical name
Trade name
Structural formula
Physico-chemical properties 5-7
1) Real specific gravity 5
2) Apparent density
3) Equilibrium moisture content
4) Permeability to moisture 6
5) Viscometric properties
a) Viscosity of aqueous solution
b) Viscosity of organic solvent solutions
6) Properties of the film 7
Specifications and test methods 8
Applications 9
1) Technique for dissolving PHARMACOAT
a) Dissolving in water
b) Dissolving in organic solvents
2) Film coating
3) Dissolution characteristics of PHARMACOAT-coated tablets
4) Granulation
Packaging, Outline of applications 10
PHARMACOAT-related products 11

Please note:
• The information and data contained herein are believed to be correct and are given
in good faith. However, no liability is accepted therefore, and no warranty or free-
dom from any patent is to be inferred.
• The general specifications for the products are those in use at the time of printing of
this brochure and are subject to change in the future.
• Please contact us if you have any questions or require more information.
 PHARMACOAT: PREFACE 3

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 font 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, non-ionic 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. Detailed technical information is available in a separate
publication, “Technical Information”.
 PHARMACOAT: DESIGNATION & STRUCTURAL FORMULA 4

Hypromellose (Hydroxypropyl Methylcellulose: HPMC)

Designation Substitution Type 2910(USP)
Substitution Type 2208(USP)
Admissions to
USP, EP
Compendia
Cellulose, 2-hydroxypropyl methyl ether
Chemical name
(CAS 9004-65-3)

Trade name Pharmacoat

Grade
Substitution Labelled Viscosity
Normal Granular White
Type (cP)*
Type Type Type
603 - 603W 3
- - 645W 4.5
2910
Pharmacoat 606 606G 606W 6
615 - - 15
904 - - 2208 4

Structural
formula
 PHARMACOAT: PHYSICO-CHEMICAL PROPERTIES 5

1) Real specific gravity 1.26-1.31

2) Apparent density 0.5-0.7 g/ml (tapped)

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.
Fig. 1: Relative humidity and equilibrium moisture content at 25°

3) Equilibrium moisture
content

Table 1: Permeability to moisture of film

Material Moisture permeability

PHARMACOAT 603 207
4) Permeability to
PHARMACOAT 606 194
moisture
PHARMACOAT 615 192

unit: g/m2·24 hr-0~75% difference in RH

25°C, 0.1 mm thickness
 PHARMACOAT: PHYSICO-CHEMICAL PROPERTIES 6

Fig. 2: Concentration-viscosity relationship of PHARMACOAT

5) Viscometric properties

a) Viscosity of aqueous solution

The relationship between concentration and

viscosity of PHARMACOAT 603, 645W, 606, and
615 in water at 20°C and 40°C is shown in Fig.2.
The type of product and the concentration used
should be selected depending on the required
usage. For film coating, concentrations reaching
80-100mPa~s are optimum. For use as a binder,
a low viscosity grade is effective.

b) Viscosity of organic solvent solutions

PHARMACOAT is soluble in aqueous alcohols such

as ethanol and isopropanol containing water in a
ratio of more than 1:1, but insoluble in simple
alcohols. Organic solutions can be prepared in
mixtures of methylene chloride and alcohol.
There are various disadvantages to the use of
organic solvents in pharmaceutical processing,
but if they must be used, we recommend
methylene chloride-ethanol and water-ethanol
mixtures as solvents.
 PHARMACOAT: PHYSICO-CHEMICAL PROPERTIES 7

6) Properties of the film Therefore, when an inorganic substance is added,

use of a grade with a relatively high viscosity
PHARMACOAT film has the hardness and strength (molecular weight) such as PHARMACOAT 645W
characteristic of cellulose derivatives. Although 606 or 615 is recommended. Moreover, addition of
PHARMACOAT film is not brittle, as acrylic polymer a water-insoluble polymer such as ethylcellulose
is, addition of a plasticizer such as polyethylene (EC) or hydroxypropyl methylcellulose phthlate
glycol (PEG 6,000) is effective when highly flexible (HPMCP) to PHARMACOAT delays dissolution of the
film is required. film, which is useful for the masking of bitter taste
When PHARMACOAT film is used for film coating, or unacceptable texture, as well as delaying drug
sometimes titanium dioxide or talc is recommended dissolution. Table 2 shows the solubility of such a
to be added. Addition of inorganic substances such mixed film in simulated gastric fluid and simulated
as TiO2 in a large amount to a grade of intestinal fluid. The test piece had a thickness of
PHARMACOAT 603 with low viscosity (molecular 0.08 mm and a size of l0mm x l0mm. For the test,
weight) causes a marked decrease in the tensile the apparatus for the USP Disintegration Test was
strength, often leading to occurrence of cracking used.
and detachment.

Table 2: Solubility of mixed film in simulated gastric fluid and simulated intestinal fluid

Simulated Simulated
Mixed film Mixing ratio
gastric fluid intestinal fluid

9/1 Soluble Soluble

8/2 Soluble Soluble

7/3 Soluble Soluble

6/4 Low Soluble

PHARMACOAT 606/HPMCP
5/5 Nearly insoluble Soluble

4/6 Nearly insoluble Soluble

3/7 Nearly insoluble Soluble

 PHARMACOAT: SPECIFICATIONS 8

PHARMACOAT meets all the requirements for USP PHARMACOAT is manufactured in accordance with the
Hydroxypropyl Methylcellulose (Substitution Type 2910 or good manufacturing practice (GMP). A certificate of
2208) or EP Hypromellose. Moreover, in addition to the analysis commonly incorporating test results based on
tests prescribed in the aforementioned Pharmacopoeias, the USP, are routinely attached to PHARMACOAT
Shin-Etsu carries out tests for foreign matter products. Quality specifications are shown in the
contamination, microbiological contamination, yellowness following table.
index, etc., in order to ensure strict quality control.

Table 3: Quality specifications of PHARMACOAT

PHARMACOAT PHARMACOAT PHARMACOAT PHARMACOAT

Item/Grade Method
603 606 615 904
Substitution type in USP 2910 2208
Description
conforms USP
and solubility
Characters conforms EP
Identification (A—C) conforms USP
(A—F) conforms EP
pH 5.5—8.0 EP
Apparent viscosity
2.4 - 3.6 4.8 - 7.2 12.0 – 18.0 3.2 – 4.8 USP or EP
(cP or mPa s)
Loss on drying not more than 5.0% USP
not more than 1.5% USP
Residue on ignition
not more than 1.0% EP
within the limit
Arsenic USP
not more than 3ppm)
within the limit
Heavy Metals USP
(not more than 0.001%)
Appearance of Solution conforms EP
within the limit
Chlorides EP
(not more than 0. 5%)
Methoxyl content 28.0 - 30.0% 19.0 - 24.0% USP
Hydoroxypropoxyl
7.0 -12.0% 4.0 -12.0% USP
content
PHARMACOAT 904 is especially useful as a binder for sugar coating in addition to its general uses as a coating
material and binder for tablets or granules.

PHARMACOAT 603W, 645W and 606W are Viscosity ranges are as follows. Other specifications
developed grades with less yellowness to the are the same as those for PHARMACOAT type 2910.
solution color.
PHARMACOAT 603W PHARMACOAT 645W PHARMACOAT 606W
Apparent viscosity
2.5 - 3.5 3.6 - 5.1 5.2 - 7.0
(cP or mPa s)
 PHARMACOAT: APPLICATIONS 9

1) Dissolving PHARMACOAT 3) Dissolution characteristics of

PHARMCOAT-coated tablets
As PHARMACOAT is a powder with a particle size
of 50-70µm, dissolution of a large amount of The coated tablets must release the drug in
PHARMACOAT must be done carefully to avoid simulated gastric fluid. Moreover, it is essential that
loss of material through dust formation (dusting). the drug is dissolved in water and buffer solutions
Moreover, as PHARMACOAT has high solubility in with various salt concentrations and pH values
water and mixed solvents, it may form lumps, similar to those of simulated gastric fluid. This is
which require a long time to dissolve, if it is because the pH value of human gastric juice shows
added to such solvents all at once. inter- individual variation depending on age,
constitution, etc. and the drug therapeutic effect is
2) Film coating required to be maintained irrespective of such
differences. PHARMACOAT film has very favourable
Film coating is usually done with aqueous solu- dissolution characteristics from this point of view,
tions rather than organic solvents, since the cost and this is one of the main reasons why
of the solvent is less, the cost of equipment is PHARMACOAT is widely used as a coating agent.
less (solvent recovery and disposal are simpler),
and the process is safer (better working In the case of agents having pH-dependent
environment, less risk of explosion and no need dissolution characteristics such as acrylic polymer
for treatment to remove residual solvents in and polyvinyl polymer, water-soluble polymers or
preparations). Accordingly, Shin-Etsu other additives may be required, but PHARMACOAT
recommends the adoption of coating with an has uniform dissolution characteristics, making it
aqueous solution. Machinery which offers a high easy to use.
drying efficiency and short coating time is
available. 4) Granulation

Many coatings are available for particular PHARMACOAT can also be used as a binder for
purposes such as improving abrasion resistance, granulation. The fine particle size (5O-7Oµm on
improving printability, improving impact strength, average) allows good admixture with the vehicle
masking colour and/or taste, and improving (lactose-corn starch) and PHARMACOAT is effective
flowability. Coating formulations and quantities for flow granulation and agitating granulation (dry
differ considerably depending on the purpose, blend).
and it is necessary to change the formulation of
the coating solution, the drying temperature and A low viscosity grade is more effective as a binder
the operating parameters of the coating for granulation. Shin-Etsu recommends the use of
equipment on a case-by-case basis. Shin-Etsu PHARMACOAT for fine granules and tabletting
Chemical can provide technical advice on the granules as a highly stable binder which does not
suitability of various coatings. interact with drugs.
 PHARMACOAT: PACKAGING, OUTLINE OF APPLICATIONS 10

• 50kg net: Double layered polythene bag in fibre drum

Packaging
• 1 kg net: Double layered polythene bag

Coating for tablets and granules

Masking of colour, masking of taste, improvement in hardness,
improvement of abrasion resistance, improvement in flowability,
improvement in stability and improvement in printability.

Undercoating for sugar coating

Waterproofing and stabilization of dissolution

Undercoating for enteric coating

Outline of Applications Prevention of reaction between drugs and coating agents

Binder for tablets and granules

Improvement in granulation yield, improvement in hardness and
prevention of interaction with drugs

Formation of membrane and increase in viscosity for

aerosols and ointments
Provision of membrane with desired properties and stabilization of
suspensions

Limitation of Applications PHARMACOAT must not be used in preparations for injection.

 PHARMACOAT: RELATED PRODUCTS 11

Regular types of hydroxypropyl methylcellulose or

methylcellulose are on sale under the trade name
METOLOSE, and are used as binders for solid
dosage forms and to increase viscosity. Data on
these products will be provided on request.

Table 8: Outline of types of hypromellose (hydroxypropyl methylcellulose) and Methylcellulose

Corresponding name defined

by USP Hypromellose Hypromellose Hypromellose
Methylcellulose
Substitution Type 2208 Substitution Type 2910 Substitution Type 2906
Labelled viscosity (USP)
3 PHARMACOAT 603, 603W
4 PHARMACOAT 904 METOLOSE SM-4
4.5 PHARMACOAT 645W
PHARMACOAT 606, 606W,
6
606G**
15 PHARMACOAT 615 SM-15
25 SM-25
50 METOLOSE 60SH-50 METOLOSE 65SH-50
100 METOLOSE 90SH-100 SM-100
400 90SH-400 65SH-400 SM-400
1500 65SH-1500 SM-1500
90SH-4000
4000 60SH-4000 65SH-4000 SM-4000
90SH-4000SR*
10000 60SH-10000
15000 90SH-15000 65SH-15000
90SH-100000
100000
90SH-100000SR*
Range of substituent content
19.0-24.0% 28.0-30.0% 27.0-30.0% 27.5-31.5%
Methoxy group
4.0-12.0% 7.0-12.0% 4.0-7.5%
Hydroxypropoxy group

* METOLOSE SR is used for Hydrophilic matrix system, having much tighter specification
** PHARMACOAT 606G is a granular type product for quick preparation of the coating solution and dust-free handling

PHARMACOAT and METOLOSE are registered trade names of Shin-Etsu Chemical Co., Ltd.
 Shin-Etsu Chemical Co.,Ltd

Cellulose & Pharmaceutical Excipients Department

6-1, Ohtemachi 2-chome, Chiyoda-ku, Tokyo, 100-0004

Japan
TEL: 8 1-3-3246-5261 FAX: 81-3-3246-5372
http://www.metolose.jp/e

Revised 2004.10 2005.2/500