CTCBIO INC.

Tadalafil Orally Soluble Film 20mg

Confidential document

Hold time study

Hold time study report of

CDFF0213
(Tadalafil Orally Soluble Film 20mg)

Project No.

CDFF0213

Document ID

PD-PS1-00

Version No.

00

CTCBIO INC.

Jul. 29, 2013

page 1 / 8

CTCBIO INC.

Tadalafil Orally Soluble Film 20mg

Confidential document

Hold time study

Revision History
Revision No.

Date of Revision

00

July 29, 2013

Details of Revision
Initial issue

Revised by
JunGi Kim

Comment
Limit for the waiting period of half-finished products was established for each process.

Investigator
Reviewed by
Approved by

Jul. 29, 2013

Product
research team
Product
research team
Product
research team

Junior
researcher
Chief
researcher
Senior
researcher

JunGi Kim (Signature)

Date: Jul. 29, 2013

SuJun Park (Signature)

Date: Jul. 29, 2013

BongSang Lee (Signature)

Date: Jul. 29, 2013

page 2 / 8

CTCBIO INC.
Confidential document

Tadalafil Orally Soluble Film 20mg

Hold time study

Contents

1. Summary ............................................................................................................................ 4
2. Purpose ............................................................................................................................... 4
3. Specimen ............................................................................................................................ 4
4. Test Period and Schedule .................................................................................................. 4
5. Test Item ............................................................................................................................. 5
6. Test Methods and Standards ............................................................................................ 5
7. Results ................................................................................................................................ 7
8. Conclusions ........................................................................................................................ 8

Jul. 29, 2013

page 3 / 8

CTCBIO INC.

Tadalafil Orally Soluble Film 20mg

Confidential document

Hold time study

1. Summary
Establishing the waiting period that is available for half-finished products in each
process of CDFF0213 (Tadalafil Orally Soluble Film 20mg)

2. Purpose
Limit for the waiting period of half-finished products in each process were established
to ensure stability of half-finished products and effective production.

3. Specimen
[Specimen]
- Tadalafil Orally Soluble Film 20mg for lab scale up test
- Lot No.: T002

4. Test Period and Schedule

Test date
Jul. 08, 2013
Jul. 10

Jul. 29, 2013

Process
Initiation of manufacturing film
solution
Transfer and coating

Duration
- Initial film solution
- Initial coating & drying

Jul. 13

- 3rd day film solution

Jul. 15

- 5th day film solution

Jul. 17

- 1st week coating & drying

Jul. 24

- 2nd week coating & drying

page 4 / 8

CTCBIO INC.

Tadalafil Orally Soluble Film 20mg

Confidential document

Hold time study

5. Test Item
Process

Test item

1. Content difference between the upper and lower

layers by time and mean weight of the film
Preparation of film solution 2. Increment of impurities by time
3. Microbial limit test by time
(only on 3rd and 5th days)
1. Confirmation of content by time
Coating & Drying
2. Confirmation of film weight by time
3. Confirmation of loss on drying by time
6. Test Methods and Standards
[Film solution manufacturing process]
(1) Collection of film solution for test
More than 1kg of finished film solution was collected and put in a 1,000-mL
measuring cylinder, covered the opening with plastic wrap and left for maximum 5
days at room temperature (25).
(The initial data of film weight and content test are replaced by those of the initial
sample in the coating & drying process.)
(2) Sample collection at each time point
For the content test on 3rd and 5th days, sample was carefully collected on the
corresponding days at 5cm from the surface and approximately 5cm from the bottom
using a pipette. Impurity test and microbial limit test were conducted using the
sample obtained from the upper layer.
(3) Drying the samples
Base films placed on a glass plate was coated with the collected samples and then
dried under the designated conditions for time and temperature. The coating and
drying conditions are as follows.
Coating thickness

460um

Drying temperature

80

Duration of drying
(4) Sample analysis

60 min.

The dried films were evenly sliced and tested for the standard of Tadalafil Orally
Soluble Film 20m and for dosage form uniformity and impurity. Microbial limit test
for the film solution was conducted following the Microbiological examination of
Jul. 29, 2013

page 5 / 8

CTCBIO INC.

Tadalafil Orally Soluble Film 20mg

Confidential document

Hold time study

nonsterile products: Microbial enumeration tests, USP <61> and the Microbiological
examination of nonsterile products: Tests for specified microorganism, USP <62>.
(5) Standards

Content test
-

The content in the initial sample and samples at each time point should be
95-105%.

The content result at each time point should not be different by more than 2%
compared with the result at the initial time point.

The content results between the upper and lower layers should not be
different by more than 2% among the samples at each time point.

The mean weight difference among 5 sites of the upper and lower layers
should not be more than 3mg among the samples at each time point.

Impurity test
-

Impurity test results at each time point should be suitable, and the difference
between the initial and each time point should not be more than 0.1% for
individual unknown impurities and 0.2% for total impurities.

Microbial limit test

-

Microbial limit test results should be suitable at each time point.

[Coating & Drying process]

(1) Preparation of coating solution for test
The manufactured film solution was dried under the condition described below and
the base films were overlapped to the upper and lower surfaces. The packaging
material that was identical to the one described in the manufacture order was used for
packaging and then the samples were left for maximum 2 weeks at room temperature
(25) (packaging performed separately for different time points).
(2) Collection and analysis of samples at each time point
Samples were collected at each time point and tested for the standard of Tadalafil
Orally Soluble Film 20m and for dosage form uniformity and impurity.
(3) Standards

Contents
-

Jul. 29, 2013

The result of content test at each time point should be 95-105%.

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CTCBIO INC.

Tadalafil Orally Soluble Film 20mg

Confidential document

Hold time study

Difference between mean content at each time point and mean content at the
initial time point should not be greater than 2%.

Difference in mean weight between each time point should not be greater
than 3mg.

Loss on drying
-

Results of loss on drying of samples at each time point, including the initial
sample, should be suitable.

Difference in the results of loss on drying between the initial and each time
point should not be greater than 3%.

7. Results
[Film solution manufacturing process]
Process

Initial

Time point
3rd day

5th day

Upper layer

99.94

99.99

99.85

Lower layer

99.76

99.78

99.63

Content difference (%)

0.19

0.21

0.22

Suitability

Suitable

Suitable

Suitable

Upper layer

120.84

120.24

120.58

Lower layer

120.38

119.74

119.82

Difference in mean weight

(mg)

0.10

0.50

0.76

Suitability

Suitable

Suitable

Suitable

Individual
known
impurities

N.D.

N.D.

N.D.

Suitability

Suitable

Suitable

Suitable

Total
impurities

N.D.

N.D.

N.D.

Suitability

Suitable

Suitable

Suitable

Microbial limit test

Not
detectable

Not
detectable

Not
detectable

Suitability

Suitable

Suitable

Suitable

Test item

Content (%)

Mean weight
of film (mg)

Manufacturing
of film solution

Impurity

Jul. 29, 2013

page 7 / 8

CTCBIO INC.

Tadalafil Orally Soluble Film 20mg

Confidential document

Hold time study

[Coating & Drying process]

Process

Coating &
Drying

Initial

Time point
1 week

2 weeks

Content (%)

100.15

100.47

100.03

Suitability

Suitable

Suitable

Suitable

Film weight (mg)

120.48mg

119.10mg

119.92mg

Suitability

Suitable

Suitable

Suitable

Loss on drying (%)

8.78

8.71

8.86

Suitability

Suitable

Suitable

Suitable

Test item

8. Conclusions
In this hold time study for manufacturing process of film solution and coating &
drying processes, the quality of half-finished products was not significantly reduced
by 5 days after completing the manufacturing process of film solution and by 2 weeks
after completing the coating & drying process.

These results indicate that the quality will be maintained up to the standard for 5 days
after completing the manufacturing process of film solution and for 2 weeks after
completing the coating & drying process. Therefore, the maximum storage time
before proceeding to the next process shall be 5 days and 14 days, respectively, after
the manufacturing process of film solution and after coating & drying process.

The maximum storage time after the coating & drying process refers to the period
until just before the packaging process, and the slitting process shall be completed
within the 14 days of maximum storage time.

Jul. 29, 2013

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