High tablettability and good disintegration of novel poly(vinylalcohol-acrylicacid-methylmethacrylate) (POVACOAT®) as a granulation binderShunji Uramatsu1, 3*, Toshinobu Uemura1,3 , Toshio Shimamoto1,Dongchun Liu2, Xing Tang2, Hideki Ichikawa3, Yoshinobu Fukumori3
1

Daido Chemical Corporation, 2 Shenyang Pharmaceutical University,
3
Kobe Gakuin University, Faculty of Pharmaceutical Sciences

Abstract
Purpose: POVACOAT is a newly developed aqueous polymer which is poly (vinyl alcohol) derivative grafted with acrylicacid and methyl methacrylate. POVACOAT is applied to coating film, granulation binder and solid dispersion carrier etc.
This study was focused on the applicability as a granulation binder. Methods: In order to elucidate the wet granulation
tendency of POVACOAT, the solid-liquid-air packing states of wet massing were evaluated by a mixer torque rheometer(MTR). Hydroxypropylcellulose (HPC-L) was used for comparison. In the next step, the granules obtained with varying thebinder liquid amounts were evaluated with regard to tablettability and disintegration. Results: Torque profiles by a MTR
suggested that the amounts of POVACOAT as a binder liquid for obtaining the optimized tabletting granules were smaller
than that of HPC-L. The tablettability which is defined as tablet hardness against tablet density with varying tablettingpressures was found to be superior in POVACOAT against HPC-L. The disintegration times of tablets were rather faster thanthat of HPC-L in spite of the higher tablet hardness. These results demonstrated that POVACOAT has an excellent
performance as a wet granulation binder with a good balance between the tablettability and disintegration
Keywords: POVACOAT, pharmaceutical excipient, granulation binder, tablettability, disintegration

1. Introduction
POVACOAT 1) is a newly developed aqueouspolymer which is poly (vinyl alcohol) derivative
grafted with acrylic acid and methyl methacrylate.
The chemical structure is shown in Fig.1.
POVACOAT is applied to coating film2), granulation
binder2,3), solid dispersion carrier4,5) and so on.
POVACOAT was registered to Drug Master Files of
US as DMF18033, and Master Files of Japan as219MF20003.
Recently, various oral disintegration (OD)
tablets have been developed6) and the conceptof Design Space (DS) was introduced inpharmaceutical formulation design technology.
The granulation binder is well-known as
taking an important role for the quality oftablet.
This study was focused on the applicabilityof novel POVACOAT as a wet granulation
binder.

Fig.1 Chemical structure of POVACOAT

2. Materials and methods
2.1. Materials
POVACOAT (Type F and Type MP (D50; 125µm),
Daido Chemical Corp., Japan), hydroxypropyl
cellulose (HPC-L, Nippon Soda, Japan), lactose(200M, DMV, Japan), and corn starch (Nippon Starch
Chemical, Japan.) were used.
*Corresponding author. Address: Shunji Uramatsu
Daido Chemical Corporation,
4-4-28 Takeshima, Nishiyodogawa-ku, Osaka, Japan.
Tel: +81-6-6471-0594. Fax.: +81-6-6471-4718
E-mail: uramatsu@daido-chem.co.jp

2.2. Equipments
Granulating torque measurement
A mixer torque rheometer (MTR; Caleva, UK) wasused.
Kneading
Forty grams of granules with varying the amounts ofbinder liquid were prepared with kneading by aMTR.
Tabletting
A rotary press (8mmφ 7R, 200mg tablet, Kikusui
Seisakusho, Japan) was used.
2.3. Evaluation methods
Powder properties as a tabletting granuleMean particle size (D50) and geometric standard
deviation (σg) as a sharpness of particle size
distribution and compression index (CI) as a
flowability of powder were measured.
Tablet hardness and disintegration
Tablet hardness was measured by Schleuniger
hardness tester. Disintegration time was measured
according to JP16 disintegration test method (37°C,900mL of purified water, non-disk).
3. Results and discussion
3.1. Solid-liquid-air packing (SLA) state
Lactose/corn starch with the weight ratio of 7/3
which is well-known as a standard formulation in
Japan was used as a model formulation. An aqueous
POVACOAT solution (6 w/v %) and an aqueous
HPC-L solution (6 w/v %) were used as a binderliquid.
In Fig. 2, SLA result of the case of using
POVACOAT was compared with that of HPC-L.
SLA measurement by a MTR was fast; it can beachieved for ca. 15 min. The amount of binder liquid
which denotes torque maximum is very importantvalue, the so-called “a plasticity limit value (PL)”.

0. 5Torque (Nm)

0. 4
0. 3
0. 2
0. 1
0. 00510152025303540Added a m ou n t s of b in der l iqu i d(w t % )P OV A 6 w t %TH and disintegration time (DT) at various ρagainst Ig is plotted in Fig. 4 for the results ofPOVACOAT (a) and that of HPC-L (b). The ρ valuesof 1.36, 1.38, 1.40 and 1.42 correspond to thetabletting pressures (kN) of 7.1, 8.2, 9.4 and 10.6,
respectively. From Fig. 4, it can be seen thatapparently the higher TH was obtained at near 0.6 ofIg as similar to the case of powder properties. Thismight be very interesting insight that the amounts ofbinder liquid for obtaining an optimized tabletting
powder and TH exist in almost the same Ig.

H PC -L 6 wt %14.0a) POVACOAT270b) HPC-LFig.2 Comparison of torque pattern
3.2. Granulation growth according to Ig
For comparison among various granulation,normalized Ig defined as an arbitrary binder liquidamount vs. PL is well used as a parameter, andgranulation growth is said to effectively occur in therange of 0.5~0.85 of Ig7). The results of Fig. 2suggest that the granulation growth of POVACOAT
might occur in a smaller amount of binder liquid thanHPC-L. In Fig. 3a), mean particle sizes (D50) of thegranules obtained with varying the amounts of binder
liquid are plotted against Ig, i.e., normalized amountof binder liquid.
50.0a)
CI

400

0.5

40.0
35.0

0.4

30.0
25.0

200

0.3

20.0
4.0

σgD50

300

0.6b)

45.0

0.2

3.0
15.0

100

2.0
10.0
1.0
5.0

0.1

0

0.0

0.0

00.2 0.4 0.6

0.8

11.2 1.4

00.2

0.4

0.8

11.21.4Ig (-)

I g (-)POVA D50
POVA

0.6

Torque (Nm)500

HPC-L D50
HPC-L

POVA σg

HPC -L σg

POVA CI

HPC-L CI

POV A

HPC-L

Fig.3 Plots of D50 and torque pattern (a) and plots ofσg, CI and torque pattern (b) as a function of Ig
In both cases, D50 sharply increased around 0.55 ofIg (Fig. 3a) and smaller σg or CI that denotes theappropriate property as a tabletting granule wasfound to be obtained in the same Ig region (Fig. 3b).
From these results, the liquid amount required for
obtaining the optimized granules of POVACOAT canbe said to be smaller than those of HPC-L. Thislesser liquid amount might be due the better
wettability of POVACOAT.
3.3. Tablet hardness (TH) and disintegration
The obtained granules with varying Ig weretabletted under various pressures. In this study, thetablettability was discussed not by the plot of TH vs.
tabletting pressure but the plot of TH vs. tablet
density8) (ρ; g/cm3) for the sake of quantitativedescription of tablettability. TH against ρ withvarying tabletting pressures was found to show alinear relationship (data not shown).

Tablet hardness (kp)

12.0

225
10.0

180

8.0
6.0

135

4.090
2.0

Disintegration time (sec)

The PL of POVACOAT was 21.0 wt% which was
26% smaller than that of HPC-L, i.e., 28.6 wt%.

45

0.0

0.2 0.3 0.4 0.5

0.6 0.7 0.8 0.9

Ig (-)

0.2 0.3 0.4 0.5

0.6 0.7 0.8 0.9

Ig (-)TH (ρ); ◆ 1.36, ■ 1.38, ▲ 1.40, ● 1.42
DT (ρ); ◇ 1.36, □ 1.38, △ 1.40, ○ 1.42

Fig.4 Tablet hardness and disintegration time
As shown in Fig. 4, TH of POVACOAT was found tobe larger than that of HPC-L, and its Ig range giving
higher TH was broad over 0.5~0.7. Disintegration
time of tablet with POVACOAT was gradually
increased with increasing Ig, while that with HPC-L
showed a sharp increase beyond 0.6 of Ig. In spite ofthe higher TH, the DT of POVACOAT tablet wasshorter than that of HPC-L tablet.
4. Conclusions
1) Binder liquid amount for obtaining the optimized
tabletting granules using POVACOAT is smaller andbroader than that of HPC-L.
2) POVACOAT has a higher tablettabilty and good
disintegration tendency; a good balance between
them can be obtained in the broad range of Ig.
3) POVACOAT as wet granulation binder is expected
to take a valuable role in dosage form design.
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H. Ichikawa,Y. Fukumori, 1st Asian Pharmaceutical
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