comparison on physical property, dissolution and disintegration of four launched orally...

RESEARCH ARTICLE

Comparison on physical property, dissolution and disintegrationof four launched orally disintegration film (ODF) productsfor erectile dysfunction

Minjun Kwon • Han Kang • Jun Hyun Ahn • Wonkyung Cho •

Bokyung Sun • Sung-Joo Hwang

Received: 10 February 2014 / Accepted: 4 April 2014

� The Korean Society of Pharmaceutical Sciences and Technology 2014

Abstract Commercially available orally disintegration

films (ODF) for erectile dysfunction were Viagra L� 50 and

100 mg by Pfizer Pharmaceuticals Korea Ltd., and Mvix S�

50 and 100 mg by SK Chemicals Co. The comparative

studies of physical property, disintegration and dissolution

time of four ODFs were carried out to evaluate film formu-

lation. For film physical property, thickness and weight

uniformity, tensile strength, dissolving pH, hygroscopicity,

morphology, flexibility and polymeric characteristics were

investigated. In vitro disintegration studies were imple-

mented by six methods. Conventional disintegration method

was carried out using USP disintegration apparatus. One side

disintegration method and both side disintegration method

were performed by using shaking water bath. Slide frame

disintegration method was conducted by contact angle

measurement. Mouth disintegration method was performed

by using two different mediums. One medium was a-amy-

lase free medium, another was add a-amylase. In vitro dis-

solution studies were carried out using pH 2.0 HCl and pH

6.8 PBS. The results were validated statistically. Film

thickness of Mvix S� 50 and 100 mg was thinner than that of

Viagra L 50 and 100 mg, respectively. Film tensile strength

of Mvix S� 50 mg and 100 mg was much higher than that of

Viagra L 50 and 100 mg. However, Viagra L� 50 and

100 mg were more flexible so that it is easier to carry and

store. High hygroscopicity and high porosity in Viagra L�

could contribute to disintegrate film quickly. In six kinds of

disintegration studies, both Viagra L� 50 and 100 mg

showed not only muche faster disintegration time but also

much faster dissolution rate.

Keywords Viagra L� � Mvix S� �Orally disintegration film (ODF) � Disintegration �Dissolution � Physical property

Introduction

Sildenafil citrate is chemically known as 1-[4-ethoxy-3-(6,7-

dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo [4,3-d]pyr-

imidin-5-yl) phenylsulfonyl]-4-methylpiperazine citrate

(Sawatdee and Srichana 2013). Chemical structure of sil-

denafil citrate is shown in Fig. 1A. It is a selective phos-

phodiesterase type 5 inhibitor that is used for the treatment of

male erectile dysfunction (Dunn et al. 2004). Viagra� tablet

(Pfizer Inc. New York, USA) is the most popular drug and

has been the most widely used drug for erectile dysfunction

(Othman et al. 2004). Viagra L� (Pfizer Pharmaceuticals

Korea Ltd., Seoul, Republic of Korea), an ODF form of

sildenafil, has been sold in Republic of Korea since 2013.

Doses for Viagra L� are same as doses of Viagra� tablet in

the market are at 50 and 100 mg.

Mirodenafil is 5-ethyl-2-{5-[4-(2-hydroxyethyl)pipera-

zine-1-sulfonyl]-2-propoxyphenyl}-7-propyl-3,5-dihydro-

pyrrolo[3,2-d]pyrimidin-4-one. Chemical structure of

mirodenafil is shown in Fig. 1B. Mirodenafil was devel-

oped to alleviate the side effects of phosphodiesterase type

5 inhibitor: dyspepsia, flushing, headache, and nasal con-

gestion (Choi et al. 2009). Mirodenafil has been marketed

in Republic of Korea under product names of Mvix� and

Mvix S� (SK Chemicals Co., Ltd, Kyunggido, Republic of

M. Kwon � H. Kang � J. H. Ahn � W. Cho � B. Sun �S.-J. Hwang (&)

Yonsei Institute of Pharmaceutical Sciences, Yonsei University,

Yeonsu-gu, Inchon 406-840, Korea

e-mail: [email protected]

M. Kwon � H. Kang � J. H. Ahn � B. Sun � S.-J. Hwang

College of Pharmacy, Yonsei University, Yeonsu-gu, Inchon

406-840, Korea

123

Journal of Pharmaceutical Investigation

DOI 10.1007/s40005-014-0127-2

Korea) which are in the tablet form and ODF, respectively.

Doses of Mvix� and Mvix S� are 50 and 100 mg.

Orally disintegrating film (ODF) is a solid form that dis-

integrates orally, not requiring water when swallowed (Liew

et al. 2012). ODF’s other names are oral disintegrating film,

orodispersible film, and orally dissolving film. Using ODF

may be advantageous, for it substitutes tablets, capsules, and

any other oral administration forms, providing convenience

and simple administration to the patients (Patel et al. 2011;

Wagh et al. 2011). ODF provides benefits in pediatrics and

geriatrics by minimizing choking risks, as younger and older

patients face difficulties swallowing tablets and capsules (Preis

et al. 2012). ODF is disintegrated in mouth, and then, active

pharmaceutical ingredients (API) are absorbed in gastroin-

testinal track (GI track) or in the mucosal membrane of cavity

(Bhyan et al. 2011; Parejiya et al. 2012). Disintegration time of

ODF is the most important factor. As ODF is taken without

water, long disintegration time of ODF attenuates its benefit.

However, there is no designated regulation for disintegration

time of the ODF product (Bhyan et al. 2011). Nevertheless,

according to the European Pharmacopoeia, disintegration time

for orodispersible tablet (ODT) is within 180 s (Bandari et al.

2008). To achieve similar effect in ODF, ODF needs to be

disintegrated in mouth within similar time as ODT.

In the present study, the physical properties, disintegration

time and dissolution of ODF formulations of two marketed

products, Viagra L� and Mvix S�, were compared to evaluate

these two formulations that have both been recently developed

and released on the market for erectile dysfunction. Since

there is no designated guidance for the ODF disintegration

time, various disintegration methods were carried out to pro-

vide basic information about the ODF formulation.

Materials and methods

Materials

Viagra L� 50 mg, Viagra L� 100 mg (Pfizer Pharmaceuticals

Korea Ltd., Seoul, Republic of Korea) and Mvix S� 50 mg,

Mvix S� 100 mg (SK Chemicals Co., Ltd, Kyunggido,

Republic of Korea) were kindly supplied by the Pfizer Phar-

maceuticals Korea Ltd. (Seoul, Republic of Korea). Sildenafil

citrate was obtained from Seoul Pharma Co., Ltd. (Seoul,

Republic of Korea). Mirodenafil was attained from the SK

Chemicals Co., Ltd (Kyunggido, Republic of Korea).

Ammonium acetate, potassium phosphate monobasic and

sodium phosphate dibasic 12H2O were purchased from

Samchun Pure Chemical Co., Ltd. (Kyunggido, Republic of

Korea). HPLC grade acetonitrile was manufactured by SK

Chemicals (Kyunggido, Republic of Korea).

Film appearance study

The thickness was determined by micrometer (Absolute

Digimatic Thickness Gauge 547-300S, Mitutoyo, Ka-

wakaki, Japan) (Basu et al. 2014). Five points, four edges

and the center, of the film were measured for each film

(Janßen et al. 2012; Liew et al. 2012; Chakraborty et al.

2013) (n = 5).

The weight was measured by micro scales (Microbal-

ance XS205DUV, Mettler-Toledo, Greifensee, Switzer-

land). The weight of sample was calculated according to

the Eq. (1) below, because film has relatively high hygro-

scopicity (Lodhi et al. 2013) (n = 5).

Film weight ¼ Film þ film packageð Þ � film package

ð1Þ

Film tensile strength study

Tensile strength was measured by rheometer (Sun Rhe-

ometer CR-500DX, Sun Scientific Co., Ltd. Tokyo, Japan).

The samples of ODF at dimension of 12 9 20 mm2 were

held vertically between two clamp that are 12 mm apart

from each other. The ODF was pulled by the clamp at a

rate of 300 mm/min and contact force of 2 kg. Test was

proceeded at 26 �C and 37 % humidity. Temperature and

humidity were controlled by a thermo-hygrostat (Zephyrus

SCA-A005WU1, Shinsung engineering, Seoul, Republic of

Korea). Tensile strength of ODF was affected heavily by

Fig. 1 Chemical structure of

sildenafil citrate and mirodenafil

M. Kwon et al.

123

the humidity, so the test was done by reducing the

humidity. The tensile strength was defined as the maximum

load cell force that is needed to break the ODF. The cal-

culation of tensile strength is shown in the Eq. (2) (Ke-

shavarao et al. 2011; Mishra and Amin 2011; Siddiqui et al.

2011; Janßen et al. 2012; Liew et al. 2012; Mahtre 2012).

Tensile Strength ¼ Load at failure

Film thickness� film widthð2Þ

Film dissolving pH study

The pH of film was determined by pH meter (S20-KS Seven

Easy, Mettler-Toledo, Greifensee, Switzerland). Each sam-

ple of ODF formulation was placed in 50 ml conical tube

filled with 10 ml distilled water (pH 8.06) and sonicated for

10 min. (n = 5) (Kunte and Tandale 2010, Mahtre 2012).

Hygroscopicity study

The hygroscopicity of ODF was determined by moisture

analysis instrument (Moisture Analysure MX-50, A&D,

Tokyo, Japan). The samples of ODF were placed in petri

dish and were stored in 40 �C and under the humidity of

75 % RH for 10 min (Kathpalia et al. 2013). Then the

sample of ODF was put into the moisture analysis instru-

ment at 60 �C for 15 min. Loss on drying (LOD) of ODF

was measured as percentage (n = 5).

Film morphology study

The film morphological images of ODF were obtained by

using a field emission scanning electron microscopy (JSM-

7100F, JEOL, Tokyo, Japan) at 5.0 kV accelerating volt-

age. ODF was cut into the small pieces and fixed on to the

metal disk with double-sided tape (3 M, Seoul, Republic of

Korea). The both side images of samples were taken (Liew

et al. 2012; Mahtre 2012; Preis et al. 2012).

Folding endurance study

Folding endurance test method was shown in Fig. 2. The

flexibility of ODF was determined by folding endurance.

After ODF was folded on polypropylene board, the 500 g

weight was placed on folded part for two seconds. ODF

was repeatedly folded back and forth at the same place

until ODF was entirely divided. Test was proceeded at

room temperature (RT) (27 �C) and humidity of 29 %.

(n = 5) (Keshavarao et al. 2011; Liew et al. 2012) (n = 5).

Film polymer characteristic study

Polymer of films was characterized by differential scanning

calorimeter (Auto DSC Q2000, TA instrument, New castle,

USA) (Tung et al. 2014). Pieces of 3–6 mg films were

accurately weighed and sealed in aluminum pan for DSC.

The analysis was performed under high purity nitrogen

(99.999 %) purge over 0–220 �C at heating rate of 10 �C/

min. Flow rate of high purity nitrogen was 40 ml/min.

In vitro disintegration time study

Six kinds of in vitro disintegration time study were per-

formed. Data were analyzed by using IBM SPSS statistics

21 software (IBM, New York, USA). One-way analysis of

variance (ANOVA) test followed by least square difference

(LSD) and Tukey’s HSD were carried out to demonstrate

statistical differences.

Conventional disintegration method

Disintegration time of the ODF using conventional disin-

tegration method was carried out by using disintegration

tester (DIT-200, Labfine, Kyunggido, Republic of Korea).

Study was performed in 1 L pH 6.8 phosphate buffer

solution (PBS) at 37.0 ± 0.5 �C and repetition per minute

between 29 and 32 of raising and lowering motion in the

immersion medium (Basu et al. 2014). Diameter of wire

mesh is 0.57–0.66 mm (Keshavarao et al. 2011; Kunte and

Tandale 2010; Liew et al. 2012). Disintegration time was

determined when all samples were passed through the sieve

(n = 5).

One side disintegration method

The one side disintegration time test was performed by

shaking water bath (BS-21, Lab Companion, Daejeon,

Republic of Korea). The one side of sample was stuck on

polypropylene board with readhesive glue stick (Scotch,

3 M, Seoul, Republic of Korea) and sample was placed on

petri dish with 20 ml pH 6.8 PBS at 37.0 ± 0.5 �C.

Shaking speed was 70 rpm. Disintegration time of ODF

was measured after film contacted medium until film was

entirely disintegrated. The test diagram of one side disin-

tegration time was shown in Fig. 3 (n = 5).

Fig. 2 Folding endurance test method. (Weight was 500 g)

ODF products for erectile dysfunction

123

Both side disintegration method

The both side disintegration time study was determined by

using shaking water bath (BS-21, Lab Companion, Daej-

eon, Republic of Korea). The samples of ODF were placed

in petri dish with 20 ml pH 6.8 PBS at 37.0 ± 0.5 �C and

was shaken at 70 rpm. The disintegration time of ODF was

measured from ODF contacted medium to ODF entirely

disintegrated (Mishra and Amin 2011; Janßen et al. 2012;

Mahtre 2012; Preis et al. 2012) (n = 5).

Slide frame disintegration method

The slide frame disintegration time of ODF was obtained

by contact angle measurement (FM40MK2 Easy Drop,

Kruss GmbH, Hamburg, Germany). The drop of distilled

water was 10 ll at interval of 5 s and was dropped on

200 mm from sample of ODF. The disintegration time of

ODF was measured as the time that was needed for the film

to break or dissolve by drops of distilled water. The

mimetic diagram of slide frame disintegration test was

shown in Fig. 4 (Mishra and Amin 2011; Janßen et al.

2012; Preis et al. 2012) (n = 5).

Mouth disintegration method

a-Amylase free medium Shaking incubator (SI-600R, Lab

Companion, Daejeon, Republic of Korea) was used for

mouth disintegration time test. The No. 35 sieve (pore

size = 500 lm) was installed in 500 ml beaker on 55 mm

heights at the bottom of the beaker. The beaker was filled

with 300 ml pH 6.8 PBS at 37.0 ± 0.5 �C, and was shaken

clockwise at 100 rpm. The surface of medium was analo-

gous to the upper surface of sieve. The sample of ODF was

placed on center of sieve. The disintegration time of ODF

was checked that time of disintegrated pieces of ODF

passing sieve (Keshavarao et al.) (n = 5).

Add a-amylase medium The add a-amylase disintegration

time test was similar to the a-amylase free medium disin-

tegration time test except for the medium. a-amylase was

added in pH 6.8 PBS to make 0.426 mg/ml a-amylase

medium (Nater et al. 2005) (n = 5).

In vitro dissolution study

In vitro dissolution study was performed using USP basket

method (Saini et al. 2012). The dissolution medium was pH

2.0 HCl 900 ml at 37.0 ± 0.5 �C with basket rpm of 100

according to FDA dissolution method of sildenafil citrate

(Parejiya et al. 2012). Sample time points were 1, 3, 5, 10,

20, 30, 60 min (Liew et al. 2012). Analysis of drug con-

centration was carried out by high performance liquid

chromatographic (HPLC 1290 Infinity, Agilent technolo-

gies, Santa Clara, USA). Chromatographic condition

employed a C18 column (4.6 9 250 mm) at a flow rate of

Fig. 3 a One side disintegration time test method. b Both side

disintegration time test method

Fig. 4 Image of slide frame

disintegration study. a The

fixing method of ODF. b Slide

frame disintegration test method

M. Kwon et al.

123

1.0 ml/min with a pH 7.0 mobile phase of 0.2 M ammo-

nium acetate buffer and acetonitrile (40:60 v/v) with UV

detection at 240 nm (Sawatdee and Srichana 2013)

(n = 3).

Results and discussion

Film thickness of ODFs can affect their disintegration.

Thinner film is much easier to be disintegrated in small

volume of medium like saliva, and to be quickly swallowed

without water. The results of film thickness are shown in

Table 1. Mvix S� 50 mg was the thinnest among four

products. Viagra L� 100 mg was thicker than Mvix S�

100 mg, despite the same API weight. In standard devia-

tion, Mvix S� 50 mg was bigger than Viagra L� 50 mg.

But standard deviation of Mvix S� 100 mg was not bigger

than Viagra L� 100 mg at almost zero.

Many bubbles can be incorporated in the film formed by

casting process when the casted mass has too high viscosity,

so that the film can have irregular surface and variable

weight. Weight uniformity test was presented in Table 1.

Viagra L� 50 mg and 100 mg were generally lighter than

Mvix S� 50 and 100 mg. In comparison to the weight of

Mvix S� 50 mg, that of Viagra L� 50 mg was smaller but

standard deviation of Viagra L� 50 mg was bigger. For

100 mg products, both mean and standard deviation of

weight of Viagra L� were smaller than that of Mvix S�.

Thickness per weight is also important to disintegration

time, and thickness per weight value of each film is shown

in Table 1. Thickness per weight value of Viagra L�

50 mg was higher than that of Mvix S� 50 mg and thick-

ness per weight value of Viagra L� 100 mg was also higher

than that of Mvix S� 100 mg. As a result, Viagra L� can be

expected to have short disintegration time.

Tensile strength of ODF is similar to that of tablet forms

as a hardness parameter. Tensile strength of Mvix S�

50 mg was stronger than that of Viagra L� 50 mg but

deviation of Mvix S� 50 mg was about 2 times greater than

Viagra L� 50 mg. Tensile strength of Mvix S� 100 mg

was 2 times greater than that of Viagra L� 100 mg. It is

thought that high tensile strength of Mvix S� caused to

retard its disintegration and dissolution.

The pH of dissolved ODF upon disintegrating affects

mouth by irritating oral mucosa. The pH of saliva in mouth

of normal people is in a range of 5.3–8 (Dawes 2003). If

the pH of dissolved ODF was higher or lower than that of

saliva, it can irritate oral mucosa of patients (Kunte and

Tandale 2010). Table 1 shows results of the pH test. Viagra

L� 50 mg and 100 mg had relatively low pH values

compared to those of Mvix S� products, as shown in

Table 1. For same types of API products, pH values of

dissolved ODF were almost universal without reference to

weight of ODF and API, thickness of ODF and volume of

excipients. It was assumed that API determined the pH of

ODF in mouth.

The ODF was made of hydrophilic polymers like pull-

uan, starch, HPMC, and so on (Kulkarni et al. 2010;

Chauhan et al. 2012). The hydrophilic polymers achieve

rapid disintegration in mouth and provide good mouth

feeling to the patient. Viagra L� 50 mg had the highest

hygroscopicity among four products. Two different API

volume products of Viagra L� had higher hygroscopicity

compared to Mvix S�. Upshot of LOD was shown in

Table 1. The products containing 100 mg API had lower

hygroscopicity compared to those containing 50 mg API.

High hygroscopicity of the film means that the film has

highly wettable in medium or mouth. Thus, Viagra L� can

be disintegrated fast as compared to Mvix S�.

Morphology of ODF was shown in Fig. 5. Forward

surface of Mvix S� 50 mg (Fig. 5b) was relatively flat

compared to forward surface of Viagra L� 50 mg

(Fig. 5d). Back side of Mvix S� 50 mg (Fig. 5a) has few

holes not to be eliminated in making process. Viagra L�

50 mg was not even and had a lot of pores. Both sides of

Viagra L� 50 mg were not uniform. Mvix S� 100 mg had

flat and even forward surface (Fig. 5e) but the back of

Mvix S� 100 mg (Fig. 5f) was rough and irregular. Surface

of Viagra L� 100 mg (Fig. 5g, h) was less rough than that

of Viagra L� 50 mg but compared to the surface of Mvix

S� 100 mg, that of Viagra L� 100 mg was coarser. In sum,

the back of ODF was more rough and irregular than the

Table 1 The physical properties of ODF (n = 5)

Mean ± SD Mvix S� 50 mg Viagra L� 50 mg Mvix S� 100 mg Viagra L� 100 mg

Thickness (lm) 112.2 ± 1.64 145.2 ± 1.30 166.0 ± 0.00 223.6 ± 2.30

Weight (mg) 118.5 ± 2.00 112.7 ± 3.90 230.5 ± 2.10 216.8 ± 1.20

Thickness per weight (lm/mg) 0.9468 1.2884 0.7202 1.0314

Tensile strength (g/cm2) 276.7 ± 63.50 184.0 ± 36.19 440.6 ± 82.32 224.6 ± 58.12

pH 7.2 ± 0.49 4.8 ± 0.06 7.5 ± 0.16 4.7 ± 0.03

LOD (%) 3.5 ± 0.2 6.2 ± 1.0 2.9 ± 0.8 5.0 ± 0.6

Folding endurance (number) 1.6 ± 0.55 135.2 ± 25.97 2 ± 0.00 4.4 ± 1.34


123

front of ODF. It was assumed that in solvent state, bubbles

did not escape from solvent as a result of high viscosity of

film solvent in making progress. The rate of absorption was

a very important factor to disintegrating time in mouth. The

pore allowed the film to absorb the medium better, hence

allowing for a much faster disintegration.

Fig. 5 SEM image of ODF. a, b were each back and forward face of Mvix S� 50 mg. c, d were Viagra L� 50 mg image, separately back and

forward side. e, f were back and forward image of Mvix S� 100 mg. Images of Viagra L� 100 mg were g, h each back and forward surface

M. Kwon et al.

123

Fig

.6

DS

Cd

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vix

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50

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,b

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ixS

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,c

Via

gra

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gra

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123

The folding endurance of ODF determines the flexibility

of film. The flexibility was an important factor that can

make easy for carry and could minimize a loss of fragment

when the case was opened. Results of folding endurance

test were shown in Table 1. In Viagra L� 50 mg test,

folding number was highest among four products. Breaking

appearance was different for each product. Viagra L�

50 mg and Viagra L� 100 mg were cut at the time when

they were divided but Mvix S� 50 mg and Mvix S�

100 mg were collapsed when ODF was divided into two

pieces. The majority of Mvix S� 50 mg and Mvix S�

100 mg was broken at one backward and forward. Viagra

L� 50 mg was mostly broken at one back and forth folding,

but particular faces of Viagra L� 50 mg were not cut

entirely until the film was folded 100 times. Hence, Viagra

L� 50 mg was the most flexible among four different

products.

DSC data were shown in Fig. 6. Sildenafil citrate was

melted on 185–193 �C and mirodenafil was melted on

138–144 �C. In Fig. 6a and b, Mvix S� 50 mg and Mvix

S� 100 mg were melted on 144–150 �C. The melting

peaks of Mvix S� products were taken as melting peak of

mirodenafil. In Fig. 6c and d, melting peaks of Viagra L�

products were taken as melting peak of sildenafil citrate.

For this reason, polymer and API were considered to exist

separately in Mvix S� and Viagra L�. Polymer of Mvix S�

has broad melting point. However, polymer of Viagra L�

has glass transition temperature (Tg) at 53–55 �C and

crystallization temperature at 119–121 �C. It seems that

Viagra L� is noncrystal structure in RT. That is why

Viagra L� can be dissolved fast in medium and mouth.

The standard in vitro disintegration time of ODF did not

exist until now, and was indirectly measured by referring to

the in vitro disintegration time of orally disintegrating

tablets (ODT). According to the European Pharmacopeia

(2002), ODT should disintegrate within 180 s (Shoukri

et al. 2009). Based on this definition, ODF should also

disintegrate within at least 180 s. In vitro disintegration test

approximates true disintegration time for in vivo. Hence,

having a standard disintegration time is extremely impor-

tant. If disintegration time in mouth is long, patients have

difficulty taking the drug because of bad tastes from API or

excipients. The analysis of variance from LSD and Tukey’s

HSD shows that there are differences among the products

(P \ 0.05).

Conventional disintegration test was the most general

disintegration test method. Results of conventional disin-

tegration test were shown in Table 2. In multiple com-

parison by LSD, there are low levels of statistical

significance (P \ 0.05) among four products. Viagra L�

50 mg had the fastest disintegration time, and the deviation

value of Viagra L� 50 mg was the lowest. Both Viagra L

50 mg and Viagra L� 100 mg were disintegrated within

180 s. However, in Mvix S� products, although standard

deviation value of Mvix S� 50 mg was high, only Mvix S�

50 mg was disintegrated within 180 s. Mvix S� 100 mg

was disintegrated after 180 s, and even took longer than

540 s.

One side disintegration test and both side disintegration

were tested in smaller medium condition compared to the

conventional disintegration test. Also, these two tests were

carried out by left–right motion unlike conventional dis-

integration test, by utilizing raising and lowering motion.

Results of one side disintegration and both side disinte-

gration test were presented each in Table 2. Both side

disintegration time was shorter than one side disintegration

time, and thus it seems that the area of contacting medium

was different for these two disintegration time tests.

In one side disintegration test, only disintegration time

of Viagra L� 50 mg was within 180 s. Disintegration time

of Mvix S� 50 mg was 6.1 times higher than that of Viagra

L� 50 mg. Mvix S� 100 mg and Viagra L� 100 mg both

took longer than 180 s, yet the time gap of two 100 mg

products was not as big as that of two 50 mg products. P-

values of multiple comparison were both zero by LSD and

Tukey’s HSD.

Mvix S� 50 mg, Viagra L� 50 mg, and Viagra L�

100 mg were disintegrated within 180 s in both side

Table 2 Disintegrating time (s) (n = 5)


Conventional method 179.2 ± 59.6 19.0 ± 2.3 673.9 ± 98.6 95.0 ± 28.7

M/V ratio 9.4 7.1

One side method 690.4 ± 24.8 113.2 ± 19.9 1297.3 ± 88.3 360.0 ± 12.2

M/V ratio 6.1 3.6

Both side method 98.6 ± 20.7 19.4 ± 2.9 710.5 ± 119.8 44.0 ± 3.0

M/V ratio 5.9 16.2

Slide frame method (number) 26.3 ± 4.3 13.8 ± 3.7 [47 37.3 ± 4.2

M/V ratio 1.9 None

M/V(Mvix S�/Viagra L�) is the ratio of the disintegration time of Mvix S� to that of Viagra L�

M. Kwon et al.

123

disintegration tests. Time gap between Mvix S� 50 mg and

Viagra L� 50 mg was 5.9 times. Disintegration time of

Viagra L� 50 mg was similar to that of the same product in

conventional disintegration test. Disintegration time of

Viagra L� 100 mg in both disintegration tests was shorter

than that of conventional disintegration test.

Slide frame disintegration test was different from other

disintegration tests because this test was under no motion

condition. Instead, slide frame disintegration test used the

gravitational force. Maximum drop number of syringe used

for dropping distilled water was 47 drops because syringe

true volume was about 470 ll. Viagra L� 50 mg was also

very easily disintegrated. However, Mvix S� 100 mg could

not be measured because Mvix S� 100 mg was not disin-

tegrated until 47 drops had fallen. Mvix S� 50 mg was

about 2 times bigger than Viagra L� 50 mg.

Mouth disintegration test was carried out by dividing

two methods. One was a-amylase free medium and the

other was adding a-amylase. Contacting medium volume

of both two tests was very low and made frictional force by

sliding ODF on sieve.

a-amylase free medium mouth disintegration test result

was shown in Table 3. Only Viagra L� 50 mg was disin-

tegrated within 180 s. Disintegration time of Mvix S�

50 mg was 713.3 s, 5.8 times higher than that of Viagra L�

50 mg (P = 0.000). Disintegration time of Mvix� S

100 mg could not be measured, but compared Viagra L�

100 mg, disintegration time of Mvix S� 100 mg was much

higher (P = 0.000).

Add a-amylase mouth disintegration test was shown in

Table 3. Disintegration time of Mvix S� 50 mg was

513.2 s and was 4.4 times longer than disintegration time

of Viagra L� 50 mg taken at 122.6 s. Mvix S� 100 mg was

disintegrated by add a-amylase mouth disintegration test,

unlike in a-amylase free medium disintegration test.

However, disintegration time of Mvix S� 100 mg was still

9.3 times higher than that of Viagra L� 100 mg.

As both two mouth disintegration test were compared,

results of Viagra L� 50 mg and Viagra L� 100 mg had

almost no difference. However, results of Mvix S� 50 mg

and Mvix S� 100 mg had difference. In case of Mvix S�

50 mg, the time for a-amylase free medium mouth disin-

tegration test was about 200 s higher than that under add

a-amylase mouth disintegration test. It seemed that Mvix

S� products created high volume of excipients that were

dissolved by a-amylase.

pH 2.0 HCl dissolution study was shown in Fig. 7 and 8.

When dissolution rate of Viagra L� 50 mg was about 100 %,

time of Viagra L� 50 mg was reached in 5 min. This was the

fastest compared to other three products. The time of about

Table 3 Mouth disintegrating time (s) with/without a-amylase (n = 5)


a-amylase free medium 713.3 ± 85.2 122.6 ± 21.5 [5400 218.9 ± 12.1

M/V ratio 5.8 None

Add a-amylase 513.2 ± 25.6 117.0 ± 22.2 2045.5 ± 274.6 219.1 ± 14.1

M/V ratio 4.4 9.3

M/V(Mvix S�/Viagra L�) is the ratio of the disintegration time of Mvix S� to that of Viagra L�

Fig. 7 Dissolution rate of Viagra L� 50 mg and Mvix S� 50 mg in

pH 2.0 HCl 900 ml


pH 2.0 HCl 900 ml


123

100 % dissolution of Viagra L� 50 mg and Mvix S� 50 mg

were respectively half of Viagra L� 100 mg and Mvix S�

100 mg. Especially, dissolution time of Mvix S� 50 mg took

5 min more than that of Viagra L� 100 mg. Absorption rate

of Viagra L� in the patient’s GI track is hence expected to be

much faster than that of Mvix S� .

The pH 6.8 PBS dissolution study was shown in Fig. 9

and 10. Compared to pH 2.0 HCl medium, in pH 6.8 PBS,

both Viagra L� and Mvix S� dissolved slowly. Viagra L�

50 mg reached about 13 % dissolution rate. However,

since ODF stayed in mouth for about 1 min, the actual

dissolution rate of Viagra L� 50 mg was below 3 %. The

dissolution rate of Mvix S� was lower than that of Viagra

L� in pH 6.8 PBS just as in pH 2.0 HCl. When patients

take the ODF, both Viagra L� and Mvix S� are expected to

be disintegrated in mouth and dissolved in stomach.

Conclusion

This study was performed for comparing physical property,

dissolution and disintegration of four film products. It was

mainly focused on investigation of how film physical

property affects disintegration time and which product was

disintegrated faster among the four products. Physical

characteristic study was shown that Viagra L� was high

wettability, because Viagra L� was more hygroscopic than

Mvix S�. Viagra L� products are relatively flexible in term

of endurance and tensile strength compared of Mvix S�

products. It seems that polymer of Viagra L� was non-

crystal structure at RT. Physical property considered,

Viagra L� is expected to fast disintegrate, and real disin-

tegration time and dissolution of Viagra L� products is

even faster than Mvix S� products. As a result, it is pre-

dicted that patient compliance of Viagra L� is better than

Mvix S�

Acknowledgments All authors (M. Kwon, H.Kang, J.H. Ahn, W.

Cho, B. Sun, S.-J. Hwang) declare that they have no conflict of

interest. This work was supported and funded by Pfizer Pharmaceu-

tical Korea Ltd., Seoul, Republic of Korea (2013-8-1071).

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