Steril-Gene Life Sciences (P). Ltd.

Puducherry
Technology transfer

TABLET SPLIT STUDY REPORT FOR HYDROCORTISONE

TITLE
TABLETS USP 5 mg
Report No. Page No. 1 of 16

TABLET SPLIT STUDY PROTOCOL

Product Name HYDROCORTISONE TABLETS USP 5 mg

Customer APPCO PHARMA

Market USA
 Steril-Gene Life Sciences (P). Ltd.
Puducherry
Technology transfer
TABLET SPLIT STUDY REPORT FOR HYDROCORTISONE
TITLE
TABLETS USP 5 mg
Report No. Page No. 2 of 16

1. TABLE OF CONTENTS

S. No. Table of contents Page No.

1.0 Table of contents 2

2.0 Document Approval 3

3.0 Objective 3

4.0 Product Details 3

5.0 Manufacturing Location and Study location 4

6.0 References 4

7.0 Tablet split plan and acceptance criteria 4

8.0 Documentation 5

9.0 Attachments 5

10.0 Revision history 5

 Steril-Gene Life Sciences (P). Ltd.
Puducherry
Technology transfer
TABLET SPLIT STUDY REPORT FOR HYDROCORTISONE
TITLE
TABLETS USP 5 mg
Report No. Page No. 3 of 16

2. DOCUMENT APPROVAL

Particulars Department Name Designation Sign Date

Technology
Prepared By
Transfer
Technology
Transfer
Reviewed By
Quality
Control

Approved By QA

3. OBJECTIVE
The objective of this report is to demonstrate that the split tablets met the desired quality attributes
as per the Guidance for Industry Tablet Scoring: Nomenclature, Labeling, and Data for Evaluation.

4. PRODUCT DETAILS

Product Name HYDROCORTISONE TABLETS USP

Strengths 5 mg

Description White to off white, round, scored, uncoated tablets debossed with “A” and
‘198’ separated by a break line and plain on the other side.

Label Claim Each uncoated tablet contains Hydrocortisone Tablets USP……. 5 mg

 Steril-Gene Life Sciences (P). Ltd.
Puducherry
Technology transfer
TABLET SPLIT STUDY REPORT FOR HYDROCORTISONE
TITLE
TABLETS USP 5 mg
Report No. Page No. 4 of 16

5. MANUFACTURING LOCATION AND STUDY LOCATION:

Department Responsibilities
Manufacturing Steril-Gene Life Sciences (P) Ltd.
Location Puducherry.
Quality control
Study location Block D
Steril-Gene Life Sciences (P) Ltd.

6. REFERENCE:

7.1. USFDA, Guidance for Industry – Tablet Scoring: Nomenclature, Labeling and data for
evaluation.
7.2. USP <1216>Tablet Friability
7.3. USP <905> Uniformity of dosage unit
7.4. USP<705> Quality attributes of tablets labeled as having a functional score.

7. TABLET SPLIT PLAN AND ACCEPTANCE CRITERIA:

S.
Sample quantity for
No Tests to be performed Acceptance Criteria
analysis
.
Tablet Split ability
1. Loss of mass – Attachment I
Non-mechanical split (by hand) 15 whole tablets NMT 3.0 %
Mechanical Split (with tablet 15 whole tablets NMT 3.0 %
splitter)
2. Friability - Attachment I
Non-mechanical split (by hand) Equivalent to 6.5 g NMT 1.0 %
Mechanical Split (with tablet
Equivalent to 6.5 g NMT 1.0 %
splitter)
3. Uniformity of dosage unit by content uniformity - Attachment I
 Steril-Gene Life Sciences (P). Ltd.
Puducherry
Technology transfer
TABLET SPLIT STUDY REPORT FOR HYDROCORTISONE
TITLE
TABLETS USP 5 mg
Report No. Page No. 5 of 16

Non-mechanical split (by hand) 10 tablets split (20 splits)

10 half tablets shall be The acceptance value (AV)
Mechanical Split (with tablet taken for CU (L1) and 10 should be less than or equal
splitter) half tablets shall be taken to 15.0
for CU (L2).

8. DOCUMENTATION
Tablet sub-division study results are report in attachment- I

9. ATTACHMENTS
Attachment – I: Tablet Split Study Record for Hydrocortisone tablets USP 5 mg.

10. REVISION HISTORY

S. No. Version No. Reason for changes CC No.

 Steril-Gene Life Sciences (P). Ltd.
Puducherry
Technology transfer
TABLET SPLIT STUDY REPORT FOR HYDROCORTISONE
TITLE
TABLETS USP 5 mg
Report No. Page No. 6 of 16

Attachment - I
Loss of Mass:

Low hardness, Target hardness and High hardness samples were split mechanically and manually (non-
mechanically) and % loss of mass was determined. The Loss of Mass data, summarized in Tables 5 to 10,
was less than 3.0 % as recommended by FDA’s Guidance for Industry, Tablet Scoring: Nomenclature,
Labeling and Data for Evaluation.

Table 5: Loss of Mass study: Non-Mechanically split tablets (by hand) on lower hardness tablets.

Whole tablet
Split tablet part 1 Split tablet part 2
weight D=B+C Loss of mass =
S. No. (mg) (mg)
(mg) (mg) (A-D/A*100)
B C
A
1

10

11

12

13

14

15

Avg.
 Steril-Gene Life Sciences (P). Ltd.
Puducherry
Technology transfer
TABLET SPLIT STUDY REPORT FOR HYDROCORTISONE
TITLE
TABLETS USP 5 mg
Report No. Page No. 7 of 16

Table 6: Loss of Mass study: Mechanically split tablets (by tablet splitter) on lower hardness
tablets.

Whole tablet
Split tablet part 1 Split tablet part 2 Loss of mass
weight
S. No. (mg) (mg) D=B+C (mg) (%) =
(mg)
B C (A-D/A*100)
A
1

10

11

12

13

14

15

Avg.
 Steril-Gene Life Sciences (P). Ltd.
Puducherry
Technology transfer
TABLET SPLIT STUDY REPORT FOR HYDROCORTISONE
TITLE
TABLETS USP 5 mg
Report No. Page No. 8 of 16

Table 7: Loss of Mass study: Non-Mechanically split tablets (by hand) on target hardness tablets

Whole tablet
Split tablet part 1 Split tablet part 2
weight D=B+C Loss of mass (%) =
S. No. (mg) (mg)
(mg) (mg) (A-D/A*100)
B C
A
1

10

11

12

13

14

15

Avg.
 Steril-Gene Life Sciences (P). Ltd.
Puducherry
Technology transfer
TABLET SPLIT STUDY REPORT FOR HYDROCORTISONE
TITLE
TABLETS USP 5 mg
Report No. Page No. 9 of 16

Table 8: Loss of Mass study: Mechanically split tablets (by tablet splitter) on target hardness
tablets

Whole tablet
Split tablet part 1 Split tablet part 2
weight D=B+C Loss of mass (%) =
S. No. (mg) (mg)
(mg) (mg) (A-D/A*100)
B C
A
1

10

11

12

13

14

15

Avg.
 Steril-Gene Life Sciences (P). Ltd.
Puducherry
Technology transfer
TABLET SPLIT STUDY REPORT FOR HYDROCORTISONE
TITLE
TABLETS USP 5 mg
Report No. Page No. 10 of 16

Table 9: Loss of Mass study: Non-Mechanically split tablets (by hand) on higher hardness tablets

Whole tablet
Split tablet part 1 Split tablet part 2
weight D=B+C Loss of mass =
S. No. (mg) (mg)
(mg) (mg) (A-D/A*100)
B C
A
1

10

11

12

13

14

15

Avg.
 Steril-Gene Life Sciences (P). Ltd.
Puducherry
Technology transfer
TABLET SPLIT STUDY REPORT FOR HYDROCORTISONE
TITLE
TABLETS USP 5 mg
Report No. Page No. 11 of 16

Table 10: Loss of Mass study: Mechanically split tablets (by tablet splitter) on higher hardness
tablets

Whole tablet
Split tablet part 1 Split tablet part 2
weight D=B+C Loss of mass =
S. No. (mg) (mg)
(mg) (mg) (A-D/A*100)
B C
A
1

10

11

12

13

14

15

Avg.
 Steril-Gene Life Sciences (P). Ltd.
Puducherry
Technology transfer
TABLET SPLIT STUDY REPORT FOR HYDROCORTISONE
TITLE
TABLETS USP 5 mg
Report No. Page No. 12 of 16

Friability:

Low hardness, target hardness and high hardness samples were split mechanically and manually (non-
mechanically) and friability of the split portions (half tablets) was determined. The friability data,
summarized in Table 8 to 10, was less than 1.0 % as recommended by FDA’s Guidance for Industry,
Tablet Scoring: Nomenclature, Labeling and Data for Evaluation.

Table 11: Friability study on lower hardness tablets

Mechanism of splitting Initial weight Final weight after 100

Friability = A-B/A*100
used (g) revolution (g)
(%)
A B
Non-Mechanical
(by hand)
Mechanical
(using tablet splitter)

Table 12: Friability study on target hardness tablets

Mechanism of splitting Initial weight Final weight after 100

Friability = A-B/A*100
used (g) revolution (g)
(%)
A B
Non-Mechanical
(by hand)
Mechanical
(using tablet splitter)

Table 13: Friability study on higher hardness tablets

Mechanism of splitting Initial weight Final weight after 100

Friability = A-B/A*100
used (g) revolution (g)
(%)
A B
Non-Mechanical
(by hand)
Mechanical
(using tablet splitter)
 Steril-Gene Life Sciences (P). Ltd.
Puducherry
Technology transfer
TABLET SPLIT STUDY REPORT FOR HYDROCORTISONE
TITLE
TABLETS USP 5 mg
Report No. Page No. 13 of 16

Uniformity of Dosage Units (by content uniformity) of split tablet portions

Target hardness samples were split mechanically and manually (non-mechanically) and Uniformity of
Dosage Units (by content uniformity) of split tablet portions was evaluated as per USP<905>. The data
summarized in Table 14 to 16 demonstrates that the data meets the requirements in USP<905> in the L1
stage. L2 stage testing was therefore not required and the table for L2 stage included in the protocol is not
applicable.

Table 14: Uniformity of dosage units (By content uniformity) of split tablets (Low hardness) – L1
Stage.

B. No
Non-Mechanically split tablets Mechanically split tablets
Split tablet No. (by Hand) (With tablet splitter)
% of Label claim* % of Label claim*

1
2
3
4
5
6
7
8
9
10

Mean
Min
Max
Std. Dev
AV value of 10
Portions
*Label Claim for half tablets is 2.5 mg
 Steril-Gene Life Sciences (P). Ltd.
Puducherry
Technology transfer
TABLET SPLIT STUDY REPORT FOR HYDROCORTISONE
TITLE
TABLETS USP 5 mg
Report No. Page No. 14 of 16

Table 15: Uniformity of dosage units (By content uniformity) of split tablets (Optimum hardness) –
L1 Stage.

B. No
Non-Mechanically split tablets Mechanically split tablets
Split tablet No. (by Hand) (With tablet splitter)
% of Label claim* % of Label claim*

1
2
3
4
5
6
7
8
9
10

Mean
Min
Max
Std. Dev
AV value of 10
Portions
*Label Claim for half tablets is 2.5 mg
 Steril-Gene Life Sciences (P). Ltd.
Puducherry
Technology transfer
TABLET SPLIT STUDY REPORT FOR HYDROCORTISONE
TITLE
TABLETS USP 5 mg
Report No. Page No. 15 of 16

Table 16: Uniformity of dosage units (By content uniformity) of split tablets (high hardness) – L1
Stage.

B. No
Non-Mechanically split tablets Mechanically split tablets
Split tablet No. (by Hand) (With tablet splitter)
% of Label claim* % of Label claim*

1
2
3
4
5
6
7
8
9
10

Mean
Min
Max
Std. Dev
AV value of 10
Portions
*Label Claim for half tablets is 2.5 mg
 Steril-Gene Life Sciences (P). Ltd.
Puducherry
Technology transfer

TABLET SPLIT STUDY REPORT FOR DEXAMETHASONE

TITLE
TABLETS USP 4 mg
Report No. SR/GEN/D-POT/040-01 Page No. 16 of 25

Conclusion:

After execution of protocol, report will be prepared and final conclusion shall be drawn.