Polyvinyl alcohol-Acrylic acid-Methyl methacrylate copolymer®
POVACOAT~~T
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Daido Chemical Corporation0~Daido Chemical Corporation~

A table of contents< Introduction >< Physicochemical properties of POVACOAT >○ Solubility○ Viscosity○ Hygroscopic property○ Thermo stability< Physical properties of POVACOAT >1) Oxygen permeability2) Moisture permeability3) Strength and elongation of film
4) High pigment volume concentration (PVC) film
< Application of POVACOAT >1) Hard capsules (PONDAC)
2) Film coating
2-1) Oxygen barrier2-2) Whisker prevention effect2-3) Elongation of film
3) Wet granulation binder
3-1) Preparation of binder liquid3-2) Granulation by using POVACOAT
3-3) Properties of granules
3-4) High tablet hardness of POVACOAT
3-5) Disintegration of tablet
4) Solid dispersion matrix< Summery of POVACOAT >< References >< Company Information >1~Daido Chemical Corporation~

< Introduction >POVACOAT (Polyvinyl alcohol/ Acrylic acid/ Methyl methacrylate copolymer) is
a novel pharmaceutical excipient. The chemical structure is shown in Fig.1.
POVACOAT is supplied as Type R with the molecular weight of 200,000 andType F with the molecular weight of 40,000. Type R is being applied to hard
capsule (PONDAC) material and Type F is being done as a material for film
coating, wet granulation binder and solid dispersion matrix, etc.

Drug Master
File No. 18033
Fig.1 Chemical structure of POVACOAT< Physicochemical properties of POVACOAT >○ Solubility: POVACOAT is soluble in water. About 30% of ethanol can be
added but the substance becomes insoluble at higher concentrations.
○ Viscosity: As seen in Fig.2, a linear relationship is shown between viscosity inlog and polymer concentration.
○ Hygroscopic property: POVACOAT is hygroscopic and the water content
increases with the increase of the relative humidity.
○ Thermo stability: POVACOAT is thermo stable between about 130°C and
220°C but is degraded above 220°C. Glass transition temperature (Tg) isobserved between about 60°C and 80°C.
100 0000

Type R

Visco sity (mPa ・ s)

10 0000
1 0000Type F

1000
100
10
1
10

15

20

25

30

Concentaratio n (w/v%)

Fig.2 Relationship between polymer concentration and viscosity
2~Daido Chemical Corporation~

< Physical properties of POVACOAT >1) Oxygen permeability
Table 1 shows the results of oxygen permeability tests. Permeability ofoxygen differs considerably and this is very remarkable characteristics of
POVACOAT membrane. Since POVACOAT can form a dense film resulting
from strong hydrogen bonding, the diffusion coefficient of oxygen is much
lower than that of other polymer film. As a result, oxygen molecules hardly
pass the film.
Table 1 Results of the oxygen permeability test
Film

Oxygen (mol/m2∙sec∙Pa)

Type R

1.80 ´ 10-15

Type F3.00 ´ 10-15

Gelatin3.35 ´ 10-6

HPMC

8.13 ´ 10-4

Measuring method; manometric visual determination (ASTM D1434)
Measurement condition; 23℃,

Film thickness; 100µm

2) Moisture permeability
In order to evaluate the moisture permeability, the aluminum casing with
the isolated film which was stuck on the opening part (40mm×40mm) wasused as seen in Fig.3. The aluminum casing was heat sealed, after 3.0g of
calcium chlorides was put into the inside as a moisture absorption agent.
The increase in weight per 24 hours of the calcium chloride under various
relative humidity was measured, and the moisture permeability coefficient
was calculated. The result is shown in Fig.4.

Isolated film
Calcium chloride

Fig.3 Appearance of test sample
3~Daido Chemical Corporation~

Moisture permeability
2
4(mg・cm/cm ・day・cmHg）×10

In the case of the hydroxypropylmethylcellulose (HPMC), the moisturepermeability coefficient is gradually increased according to relative humidity.
On the other hand, that of POVACOAT showed sigmoid type changes.
In figure the result of the addition of talc is shown together. It is clear that
POVACOAT has a good performance against moisture barrier under various
humidity conditions.
1000

HPMC
POVACOAT

100

Talc 50% (POVACOAT)
10
1
0
0

20

40

60

80

100

Relative humidity (%RH）

Fig.4 Plots of moisture permeability coefficient against relative humidity
3) Strength and elongation of film
Table 2 and 3 shows the strength and elongation of casting films. The
strength for tear of the films decreases with the increase in water content but
this decreasing tendency is not so obvious for POVACOAT Type F. With
regard to elongation, on the other hand, it can be seen that POVACOAT
stretches very well in comparison to other materials.
Table 2 Results of the strength (N/mm2) for tear of the casting films
Film

25°C / 50%RH

25°C / 75%RH

Type R

32.2

24.2

Type F

25.0

20.0

Gelatin

55.6

16.7

HPMC

30.8

14.7

Table 3 Results of the elongation in % of the casting films
Film

25°C / 50%RH

25°C / 75%RH

Type R

170

312

Type F

50

100

Gelatin

5.1

11.2

HPMC

5.1

3.2

4

~Daido Chemical Corporation~4) High pigment volume concentration (PVC) film
The strengths and elongations of POVACOAT films by varying the contentsof added TiO2 are plotted in Fig.5 and tabulated in Table 4, respectively.
It has been found that over 30 wt% TiO2 the strength of POVACOAT film isdecreased under 40%RH but it may be increased to 50 wt% while maintaining
its function as a film under a high humidity condition. In the respect ofelongation, up to 50% of TiO2 high elongation property of film is maintained.
POVACOAT film can be said to a called high PVC film. This high PVC of
POVACOAT is considered to be effective when it is used as a film coating.
Photo.1 shows the appearances of aqueous POVACOAT solution dispersed
TiO2 and that of HPMC after 24 hours. POVACOAT shows a very favorable
dispersion. This property of POVACOAT will helps well film coating
operations.
After 24Hrs. at 25℃60

at 25℃

2

Streng th (N /m m )

50
40

75%RH

30

60%RH

20

40%RH

10
0
0

10

20

30

40

50

60

C o nc. o f TiO 2 (%)

Fig.5 Relationship between concentration

POVACOAT

HPMC

Good dispersion

Sedimentation

Photo.1 Dispersion of TiO2

of TiO2 and strength of films
Table 4 Elongation in % of the film with added amounts of TiO2
Added amounts of TiO2 (w/w%)
Film

Storage

0

10

20

30

40

50

25℃60%RH

29.4

22.0

27.2

38.1

37.2

20.9

40℃75%RH
Film thickness; 50μm

59.7

60.4

63.1

73.9

72.2

51.6

POVA

condition

5~Daido Chemical Corporation~

< Application of POVACOAT >1) Hard capsules (PONDAC)
Characteristics of PONDAC are oil resistance and oxygen barrier. PONDAC
has following characteristics. This table shows comparison of 3 capsule types.
The substance allows filling of PEG 400 (macrogol) set as a design goal and isalso characterized by less generation of static electricity.
Table 5 Characteristics of PONDAC
Property

PONDAC

Gelatin

HPMC

Water content

4-6 %

13-15 %

2-5 %

Gloss

Yes

Yes

Low

Water vapor permeability

Low

Low

Low

Oxygen permeability

Very Low

Low

High

Maillard reaction with filled substance

No

Yes

No

Light degradation

No

Yes

No

Protease degradation

No

Yes

No

Static electricity

Weak

Strong

Weak

Filling of macrogol 400

Possible

Impossible

Impossible

Filling of Tween 80

Possible

Impossible

Impossible

6~Daido Chemical Corporation~

Conc. of Ascorbic acid (%)2) Film coating
2-1) Oxygen barrier
The result shows comparison with HPMC film coating using vitamin C,
which is degraded by oxygen, as a model drug. (Fig.6 The amount of coating is
10 %.) In comparison to ascorbic acid tablets coated with HPMC, deteriorationof the tablets coated with POVACOAT was prevented to the same degree asthat obtained by nitrogen substitution indicating that oxygen barrier property
was effective for film coating similarly to casting film. (See Table 1)
105◆；Noncoated tablets (in nitrogen)

100▲；Tablets coated by POVACOAT (in air)95■；Tablets coated by HPMC (in air)90●；Noncoated tablets (in air)

85
80
75

Dense film

70
0

2

4

6

8

10

12

14

16

Storage (week)

Fig.6 Stability of ascorbic acid

Photo.2 Cross section of POVACOAT film2-2) Whisker prevention effect
Whiskers appearing as needle-like crystals of the drug on the tablet surface
are a well-known problem. When occurrence of whiskers was compared byfilm coating preparations containing caffeine and potassium guaiacolsulfonate,typical examples of such formulations, HPMC coating could not prevent
occurrence of whiskers but whiskers were not observed with POVACOAT
film-coating. It was considered that the dense film of POVACOAT was thefactor that prevented occurrence of whiskers.

Noncoated tablets

Tablets coated by
HPMC

Tablets coated by
POVACOAT

Photo.3 Whisker prevention effect7~Daido Chemical Corporation~2-3) Elongation of film
Tablets of OTC drugs combined with sodium chondroitin sulfate sometimes
break as a result of swelling due to absorption of moisture. An example ofapplication of POVACOAT to such a formulation is shown. Even for a
formulation which breaks with existing HPMC as shown in the photograph,
POVACOAT film-coated tablets did not break because POVACOAT stretched
to cover swelling of the tablets.
Tablets coated by POVACOAT

after

beforeafter

Diameter; About 5% up

Tablets coated by HPMC

before

after

after

Thickness; About 14% up

Photo.4 Breakage by swelling of the tablet under 40℃75%RH 1week3) Wet granulation binder
3-1) Preparation of binder liquid
In general, re-dispersion and solubilization process of aqueous polymer istime-consuming one. It’s easy to prepare the POVACOAT aqueous solutions
for film coating or granulation binder liquid under room temperature.
The viscosities of obtained aqueous solutions of POVACOAT and otherpolymer are listed in Table 6. The viscosity of POVACOAT solution is smaller
than HPC and higher than PVP.
Table 6 Viscosity (mPa･s ) comparison among POVA, HPC-L, HPC-SL, and PVP
Conc. (w/v%)

POVA

HPC-L

HPC-SL

PVP(K-30)

6

7.1

82

33.5

4.0

9

21

375

83

6.0

12

63.5

975

260

8.0

18

370

12,740 *)1,940 *)

16.0 *)

22.2

1,525

72,100 *)8,140 *)

26.5 *)

8~Daido Chemical Corporation~*); estimated values by extrapolation

3-2) Granulation by using POVACOATIn order to evaluate the applicability of POVACOAT as a granulating binder,
granulation torque measurements were preliminarily curried out by using aMixer Torque Rheometer (MTR).Lactose/corn starch; 7/3 was used for aplacebo formulation and HPC-L was done as a comparison. Results ofmeasurements are shown in Fig 7-a).
Binder liquid amounts indicated torque maximum is called as a plasticity
limit (PL). Fig.7-a) shows a difference between PL of POVACOAT and one of
HPC-L, suggests that in POVACOAT case, an effective granule growth isoccurred at a less amounts of binder than HPC-L. For comparison among
various granulation, normalized WB (WBR: arbitrary binder liquid amountversus PL) is well used as a comparison parameter. Fig.7-b) shows the plots of
D50 at various binder amounts by using such a WBR. It is well-known fromthe studies on unit operation of granulation that granules growth (D50) is
effectively occurred among 0.5~0.85 of WBR. It was found that mean particle
size (D50) is sharply increase at about 0.6 of WBR in both cases of POVACOAT
and HPC-L from Fig.7-b).

a)

400

0.3

POVA 6wt%

0.2
0.1

0.5

b)

HPC-L 6wt%

D50；µmTorque (Nm)

0.4

HPC-L D50

500

0.4

POVA D50

300

0.3

200

0.2

100

0.1

0

0.0
0

5

10

15

20

25

30

35

Torque (Nm)

0.5

0.0
0

40

0.2

0.4

0.6

0.8

1

1.2

1.4

WB ratio (-)

Added amounts of binder liquid (wt%)

Fig.7 Torque pattern a) and granulation growth (D50) b) with added amounts of binder liquid

The PL values of drug containing
formulations cases were summarized
in Fig.8. POVACOAT binder was
suggested to be effective too in drug
containing formulations.
It is assumed that these less binder
liquid content of POVACOAT isresulting from a good wetability.

Plastic ity lim it ( w t%)

35

Drug/Placebo=1/1

30

P O V A6 %P O V A9 %P O V A1 2%
P O V A2 2. 2 %25

M P5 %HP C-L 6 %

20

S L6%
S L 1 2%15
0Placebo

2I BU

E TZ 4

Fo r mu la

PV P6%P V P 1 2%

Fig. 8 Plasticity limit (wt%) of granulation
with various formula

9~Daido Chemical Corporation~3-3) Properties of granules
Properties of tabletting granules obtained using placebo formulation withvarying WBR of various binders were summarized in Fig.9. Tabletting
granules were evaluated by D50, geometric standard deviation(σg) of particle
size distribution denoted the sharpness of particle size distribution andcompressibility index of granules (CI) corresponding to flowability of granulemass. From these figures, it was found that favorable i.e., optimized tabletting
granules in any cases were obtained at about 0.6 of WBR.
500

0.5

D50

400

PO V A D50

0.4

300

0.3

200

0.2

100

0.1

0

0.0

Torque (Nm)

D50 (µm)

HPC - L D50
HPC - SL D5 0
PV P D50
PO V AHPC - LHPC - SLPV P

00 .2 0 .4 0 .6 0 .8

1

1 .2 1 .4

WB rati o(- )0. 5

σg (-)

2. 5

0. 3

0. 2

2. 0
1. 5

0. 1

1. 0

HPC - S L σ g
PV P σ g
PO V AHPC - LHPC - S L
PV P

0. 5
0. 0
0 .2

0 .4

0 .6

0 .8

1

1 .2

PO V A C I

0.4

HPC - L C I

35
30

0.3

CI

25
20

0.2

15
10

0.1

0

1 .4

PV P C I
PO V AHPC - LHPC - S L

0.0
0

WB r atio(-)

HPC - S L C I

PV P

5

0. 0
0

40

Torque (Nm)

σg

3. 0

Torque (Nm)

HPC - L σ g

3. 5

45

PO V A σ g

0. 4

4. 0

0.5

50

4. 5

Compression Index (%)

5. 0

0 .2 0 .4 0 .6

0 .8

1

1 .2 1 .4

WB r atio(-)

17

Formulation; placebo (lactose/corn starch=7/3), Binder: 6wt% aqueous solution

Fig. 9 Relationship between granule properties and WBR3-4) High tablet hardness of POVACOATThe formability i.e., tablet hardness of optimized tabletting granules at 0.6 of
WBR which were obtained with using placebo, ibuprofen, ethenzamide, andacetaminophen were evaluated with varying tabletting pressure. The contentsof drug were 50wt% in all drugs containing formulation. In order to clarify theformability of tabletting granules quantitatively, the density of tablet obtained
at various tableting pressure was calculated by using an equation shown in
Fig.10. The plot of tablet hardness versus density is obtained such as a rightfigure in Fig.10. Accordingly, formability of tablettig granules can be estimatedby the gradient of tablet hardness versus tablet density, quantitatively.
10~Daido Chemical Corporation~

Tablet hardness (kp)

12
r
V2
V1

h
D

10

ExampleETZ, POVA12%8
64⊿Y=45.33X-50.73
r2=0.985

2
0
1.10

1.20

1.30

1.40
3

Tablet density (g/cm )Thickness（h）； h=r-((r2-（D/2)2） 1/2 、 Volume (V1) ； V1=π（h2r－h3/3）
Volume (V2) ； V2 、 Tablet volume (V)； V=2×V1＋V2
Tablet density； Tablet weight (g) / Tablet volume (cm3)

Fig.10 Calculation of the tablet density and an example of tablet hardness againsttablet density
60

11

3

[ kp/g ・cm ]⊿Tablet hardness/⊿Tablet density

Allobtained
results
of50
formabilities were summarized in40
Fig.11. In this figure, POVA MP5%
is denoted that micronized particle
30
grade of POVACOAT was used as a20
powder addition of POVACOAT MP
grade in 5%, and kneaded with10
purified water. It was found that
0
POVACOAT
hasahigherPlacebo ETZ APAP
0
1
2
3
4
formability than other polymer in
Formulaany formulations from the figure.
POVA6%
POVA12%
POVA22.2%
POVAMP5%
HPC-L6%
HPC-SL12%
About 0.1 increase of tablet density
PVP12%
is corresponded to about 250 kgf of
Fig.11 Tablet hardness tendency with using
tabletting pressure. The value of 50
various binderof gradient, for example means
about 250kgf increase of tabletting pressure makes a 5kp of increase of tablet
hardness. In case of acetaminophen (APAP) which is well known as a lessformability of API, the capping tendency of tablet was appeared up to 12% ofconcentration of POVACOAT binder solution similar to other binder. On theother hand, in the case of using a 22.2% solution or powder addition of 5% MP,
capping tendency was disappeared. It is furthermore confirmed that using ahigher concentration of POVACOAT, for example 22.2% or MP5% is useful todecrease clearly the die friction and sticking tendency.
These results show that using POVACOAT as a binder may be effective to theformulation design and to the prevention of various tabletting troublesome.
~Daido Chemical Corporation~3-5) Disintegration of tablet
The disintegration time of tablets obtained at the same density for each
formulation were evaluated. The results were summarized in Table 7. Up to12%, the disintegration time of POVACOAT was comparable to that of otherpolymer, and using POVACOAT at higher concentration of 22.2% (4% of drybase in formulation) and MP5% make large slightly in the disintegration time.
From the above mentioned formability and this disintegration results, it canbe concluded that POVACOAT is a granulating binder which has a goodbalance between the formability i.e., tablet hardness and the disintegration
Table 7 Disintegration time in sec of various formulas
PlaceboETZ

APAP

POVA 6%

85

24

38

POVA 12%

236

32

60

POVA 22.2%

182

250

211

POVA MP5%

256

130

80

HPC-L 6%

156

35

52

HPC-SL 12%

182

50

50

PVP 12%

136

20

40

Tablet density (g/cm3): placebo; 1.35, ETZ; 1.25, APAP; 1.27
JPXV, purified water

12~Daido Chemical Corporation~

MI

Load Weight

USAC

piston4) Solid dispersion matrix
POVACOAT is expected to be applicable as a solid dispersion matrix basedon its thermo plasticity. The two different preparing methods for solid
dispersion were used, i.e., a melt indexer (MI) and ultrasound assistedcompaction (USAC). The schematic diagram of MI and USAC are drawed in
Fig.12, respectively.

PowderTeflon sheet

臼cylinderfurnace

Ultrasounddie
PowderPowderdie
Lower punch

Air pressure

25mmφOrifice(Melt Indexer P-101, Toyoseiki Co, Japan)(USTM/L20 20 KHz, I.M.A. S.p.A., Italy)

Fig.12 Schematic diagram of MI and USAC
Melt indexer (MI) was used for the sake of obtaining the preliminary
information on POVACOAT solid dispersion by HME. Melt indexer is wellused in plastic industry as standard measuring equipment to characterize hot
melt plastic flow of polymer. In melt indexer various operating temperatureand over load (weight) is available, and moreover MI has a merit in which thesample amount is small in about 3g to 10g. Recently continuous twin-screw
extruder is noticed as a mass production machine in the pharmaceuticalindustry. It is expected to take variable information for applicability of
POVACOAT as a HME matrix because of a similarity of operating mechanismof MI to twin-screw extruder.
On the other hand, USAC is noticed as a novel mechanism machine for solid
dispersion preparation. Thermoplastic polymer can absorb the ultrasoundenergy and molds for very short time. Namely, USAC is assumed to be auseful machine for solid dispersion especially by applying to thermo plastic
polymer.

13~Daido Chemical Corporation~

MI experiments were carried out as follows; Samples formulated in 1/4/1 of
NIF/POVACOAT/glycerin were treated at constant weight of 2160g withvarious operating temperature. Over 160˚C, sample could be extruded
smoothly as a rod-like extrudate. When prepared at operating temperatures
above 160℃, NIF exhibited a solubility 3.7 times higher than that of NIF
crystals. Fig.13-a) denotes the comparison among POVACOAT with PVA and
PVP. All extrudate were obtained by the same operating condition, i.e., 170˚Cwith a constant weight of 2160g. It is found that POVACOAT has a goodability of solid dispersion formation in comparison with PVA or PVP.
And, USAC experiments were done as follows; Mixtures of nifedipine (NIF),
a model drug, of one part and POVACOAT of five parts were molded byultrasonic irradiation up to 670, 1000 or 1200 J. Over 1000 J, it was foundfrom differential scanning calorimetry and powder X-ray diffractometry that
NIF existed in an amorphous state, leading to a high apparent solubility of
35.6 μg/mL, which was 4.5 times higher than that of original NIF crystals (8.0μg/mL). Fig.13-b) shows a comparison of the results of POVACOAT, HPMC

MI method

40

a)

35

POVA

30
25

PVA

20

PVP

15
10

load weight 2160g

5

170 ℃

0
0

50

100

USAC method

40

150

200

Concentration of NIF (µg/mL)

C oncentra t ion of N IF (µg/mL)(TC-5) and PVP at the same operating condition (at 1000 joule) The capabilityof PVA copolymer to make nifedipine amorphous was superior to that of PVP.
These results from MI and USAC suggested that POVACOAT might beefficiently applied to solid dispersion formulation with a high performance.

b)

35

POVA
HPMC

30
25

PVP

20
15
10

NIF crystal

5
0
0

50

100

150

200

Time (min)Ti m e (mi n ）Fig.13 Solubility comparison among polymers with using MI: a) and USAC: b)

14~Daido Chemical Corporation~

< Summery of POVACOAT >The relationship between the physicochemical properties of POVACOAT and
its applicability is shown.
This relationship demonstrates that characteristics such as oxygen barrier
function, compactness of the film, stretchable property, oil resistance, thermo
plasticity, etc. are utilizable as excipients of various purposes.
Table 8 Correlation among the characteristics of POVACOAT and Application
Characteristics
Oxygen barrier

Hard

Film

Granulation

Solid

CapsuleCoating

BinderDispersion○○

High elongation○

Dense film○

Oil resistance○

Weak Static electricity

○

○

○

No Light degradation

○

○

○

○

No Maillard reaction

○

○

○

○

○

○

Adhesive on to the surfaceof granules or Tablets
Wetability○

Thermoplastic polymer○

15~Daido Chemical Corporation~

< References >1) N. Hoshi, T. Ogura, T. Shimamoto, S. Uramatsu, Development of PVA copolymer
capsules, Pharmaceutical Technology Europe, 16(4), 37-46 (2004)
2) S. Uramatsu, H. Shinike, A. Kida, T. Uemura, H. Ichikawa, Y. Fukumori,Application of poly(vinylalcohol/acrylic acid/methyl methacrylate) (PVA copolymer) asa solid dispersion matrix, 1st Asian Pharmaceutical Science and Technology
Symposium ABSTRACT BOOK, 280-282 (2007)3) S. Uramatsu, T. Uemura, S. Akiyama, H. Ichikawa, Y. Fukumori
Application of poly(vinylalcohol/acrylic acid/methyl methacrylate)(PVA copolymer) as
a wet granulation binder, AAPS Annual Meeting and Exposition, M1266, Nov. Losangels (2009)4) S. Uramatsu, T. Shimamoto, K. Kishi, S. Akiyama, T. Uemura, PVA Copolymer as a
Pharmaceutical Excipient –Characteristics and its application, Journal of Japan
Society of Pharmaceutical Machinery and Engineering, 19(2), 60-66 (2010)< Company Information >Daido Chemical Corporation
Chemical Business Department
Pharmaceutical Excipints and Cosmetic group
4-4-28, Takeshima Nishiyodogawa-ku Osaka Japan
TEL；+81-6-6471-7755
FAX；+81-6-6472-2152
HP ；http://www.daido-chem.co.jp/
E-mail ; soumu@daido-chem.co.jp(Headquarter)E-mail ; uramatsu@daido-chem.co.jp (R&D dep.)

1st edition; Sep 13, 2009
2nd edition; July 13, 201016

~Daido Chemical Corporation~