2nd Asian Pharmaceutical Science and Technology Symposium on Xi’an (2011)

High barrier function to moisture, oxygen and odor of novel poly(vinylalcohol-acrylic acid-methylmethacrylate) (POVACOAT®) as a coating filmShunji Uramatsu 1, 3*, Toshinobu Uemura 1,3, Toshio Shimamoto 1,Dongchun Liu 2, Xing Tang 2, Hideki Ichikawa 3, Yoshinobu Fukumori 3
1Daido 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 focused on the improvement of moisture permeability of POVACOAT under higher relative humidity conditions
by adding a pharmaceutical pigment. Methods: In order to evaluate the moisture permeability, the aluminum casing with
the isolated film which was attached on the opening part (40 mm × 40 mm) was used. The aluminum casing was heat-sealed,
after 3.0 g of calcium chlorides was put into the inside as a moisture absorption agent. The increase in weight per 24 hoursof the calcium chloride under various relative humidity was measured, and the moisture permeability coefficient wascalculated. Results: The moisture permeability coefficients of POVACOAT film showed a typical sigmoid change as
relative humidity increased. It was found that the permeability coefficients under higher relative humidity were excellently
modified to be in a level of 1/6 against simple POVACOAT film by adding talc.
Keywords: PVA copolymer, POVACOAT, pharmaceutical excipient, film coating, moisture permeability

1. Introduction
POVACOAT 1) is a newly developed aqueous
polymer 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 film5), granulation
binder3,5), solid dispersion carrier2,4) and so on.
POVACOAT was registered to Drug Master Files ofUS as DMF18033, and Master Files of Japan as219MF20003.
Many investigators reported that drug degradation
under higher humidity conditions occurred due tohydrolysis reaction. In this study, the moisturepermeability of simple POVACOAT film wasevaluated first. Furthermore, the improvement ofmoisture barrier tendency under relative humidity
condition, i.e., 75% R.H. at 40°C, was studied byadding commonly used pharmaceutical pigment.

aluminum casing with the isolated film which wasattached on the opening part (40 mm × 40 mm) wasused (Fig. 2). The aluminum casing was heat-sealed,
after 3.0 g of calcium chloride was put into the inside.
The increase in weight per 24 hours of the calcium
chloride under various relative humidity wasmeasured. The moisture permeability was denoted by
the coefficient of permeability in unit ofmg•cm/cm2•day•cmHg.
ground planeab

cross sections
abadcca; silicon type adhesive, b; a casting filmc; heat-seal, d; calcium chloride, e; aluminum casing

Fig. 2. Schematic diagram of moisture permeability experimentFig. 1. Chemical structure of POVACOAT

2. Materials and methods
2.1. Materials
POVACOAT (Type F; Daido Chemical Corp.,
Japan), talc (Nippon Talc, Japan) and titanium
dioxide (Toho Titanium, Japan) were used andhydroxypropylmethylcellulose (HPMC, TC5-R,
Shin-Etsu Chemical, Japan) was used as a reference
polymer. Calcium chloride (Wako Chemical, Japan)
was used as a moisture absorption agent.
2.2. Measurement of moisture permeability
In order to evaluate the moisture permeability, the*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

3. Results and discussion
3.1.Moisture permeability of simple POVACOAT film
The moisture permeability coefficients undervarious relative humidity by using the casting filmsof POVACOAT and HPMC were measured. The
results are shown in Fig. 3.
The moisture permeability coefficient of theHPMC film was gradually increased with theincrease of relative humidity while that ofPOVACOAT film showed a typical sigmoid change.
In case of lower humidity condition, POVACOAT
film is assumed to exist in lower mobility state ofpolymer segments due to strong hydrogen bonding 6).
Therefore, the diffusion coefficient of water might besmall. On the other hand, under the higher humidity
condition, for example 75% R.H., the increase ofmoisture uptake might decrease the glass transition
temperature of polymer. Accordingly the diffusion
coefficient of water is assumed to be larger.
3.2.Effect of addition of talc on moisture permeability
In order to improve the moisture permeability ofPOVACOAT under higher humidity conditions, theeffect of pigment addition was investigated. Talc andTiO2 were used as powdery additives. It was foundthat talc was very effective to decrease the moisturepermeability in a level of 1/6 against simple
POVACOAT/talc (30 w/w%) film as shown in Fig. 3.
TiO2 addition was not effective. The permeability (P)is defined from concentration of diffusant in film (S)multiply diffusion coefficient (D) of it. (P=S･D). It is
assumed that addition of talc might increase
tortuosity against diffusion pathway due to4100

102(mg・cm/cm ・day・cmHg）×10.

Moisture permeability coefficient

1000

10020

40

60

80

100

Relative humidity (%RH）◆; POVACOAT only ■; Talc 10%, ●; Talc 30%,▲; Talc 50%, ×; HPMC onlyFig. 3. Plots of moisture permeability coefficientagainst relative humidity
its sheet-like small crystalline property –awell-known modification method in film industry–,leading to the depression of moisture permeability.
The mechanical properties such as the strength andelongation of the film were confirmed to becomparable with simple POVACOT film (data notshown).
3.3. Oxygen barrier function of talc formulation
Oxygen barrier effect of POVACOAT casting film
containing 30 w/w% of talc was evaluated and theresult is shown in Fig. 4. The experiment was carriedout in the similar manner of moisture permeability
testing as follows: the mixture of ascorbic acidpowder and 1 w/w% CuSO4 as an oxidization
catalyst for ascorbic acid was put into the inside ofaluminum casing and heat-sealed. Residual contents
of ascorbic acid under storage at 40°C and 75% R.H.
were measured according to the JP assay of ascorbic
acid (titration method).
Oxygen barrier effect of 30% talc–added
POVACOAT film was found to be the same level tothe aluminum sealing as a control.
3.4. Film Coating performance of talc formulation
In order to evaluate the applicability of talc
formulations, coating experiment of tablets wascarried out by using a perforated coating machine●;POVACOAT(30w/w% talc) ■; HPMC ▲; Control(Alminum)

Fig. 4. Oxygen barrier effect of the films(Dria-coater500; Powrex Japan). Table 1
shows the operational parameters of coating.
The film coating process for talc formulation
could be achieved in the same manner ofsimple POVACOAT formulation.
Table 1. Operational parameters of coating
Feeding, Tablet size
3.9 kg, 8φ12R 200mg
Inlet / Outlet temperature
70°C / 47°C,
Inlet-air velocity3.6 m3/min
Atomize / Pattern air
120 / 110L/min
Revolution speed of drum
12 rpmSpray rate
30 g/minConcentration of solution
14%(25% aqueous ethyl alcohol) (POVA 7%,Talc 7%)
Obtained film coating tablets with varying film
amounts were stored under 40°C and 75% R.H. forthe estimation of moisture uptake of tablets. Over 5
wt% of coating amounts was found to be very
effective to moisture barrier as expected from thecasting
film
experiments.
Talc/POVACOAT
formulations are already used in the marketed
products as also an odor resistance coating film.
4. Conclusion
The moisture permeability of POVACOAT film
showed a sigmoid change as relative humidity
increased. It was found that the permeability
coefficients under higher relative humidity wereexcellently modified to be applicable to the actual
products by adding talc.
References[1] N. Hoshi, T. Ogura, T. Shimamoto, S. Uramatsu,Technology Europe, 16(4), 37-46 (2004)[2] S. Uramatsu, H. Shinike, A. Kida, T. Uemura,
H. Ichikawa,Y. Fukumori, Proceedings of 1st Asian
Pharmaceutical Science and Technology Symposium,280-282 (2007)[3]S. Uramatsu, T. Uemura, S. Akiyama,
H. Ichikawa, Y. Fukumori, AAPS Annual Meeting andExposition, M1266, Nov. Los Angels (2009)[4]T. Uemura, S. Uramatsu, S. Akiyama,
H. Ichikawa, Y. Fukumori AAPS Annual Meeting andExposition, T3385, Nov. Los Angels (2009)[5]S. Uramatsu, T. Shimamoto, K. Kishi, S. Akiyama, T.
Uemura, Journal of Japan Society of Pharmaceutical
Machinery and Engineering, 19(2), 60-66 (2010)[6]K. Nagano, S. Yamane, K. Toyoshima, POVAL,Koubunshikankoukai, Chapter 3 (1989)