BEXIMCO PHARMACEUTICALS LIMITED

TONGI - 1711, GAZIPUR, BANGLADESH

GUIDELINE

GUIDELINE NO.: G-RD-002/00

DEPARTMENT: RESEARCH AND DEVELOPMENT

PAGE NO.: 1 OF 6

TITLE: DRUG-EXCIPIENT COMPATIBILITY STUDIES

EFFECTIVE DATE: 15/07/2014

REVIEW DATE: 14/07/2016

1.0

OBJECTIVE
The objective of drug-excipient compatibility considerations and practical studies is to
delineate, as quickly as possible, real and possible interactions between potential formulation
excipients and the API. This is an important risk reduction exercise early in formulation
development.

2.0

SCOPE
This Guideline is applicable for initial studies on screening of excipients for Formulation
Development at Research & Development Department.

3.0

4.0

RESPONSIBILITY
3.1

Authorized users are responsible for carrying out the procedure.

3.2

Asst. Manager/ Sr. Asst. Manager/ and Deputy Manager, R&D or his/her nominee is
responsible for training and implementation.

ACCOUNTABILITY
4.1

5.0

Head of Research & Development Department or his/her nominee.

ABBREVIATIONS AND DEFINITIONS

R&D
API
RH

Research and Development

Active Pharmaceutical Ingredient
Relative Humidity
NAME

DESIGNATION

Abedah Nawreen

Sr. Officer, R&D

Suranjit Dhar

Deputy Manager, R&D

Afroza Akter

Sr. Asst. Manager, Quality (R&D)

Subodh Chandra Das

General Manager, R&D

PREPARED BY

CHECKED BY

APPROVED BY

FRM No.: FRD/098-00

SIGN & DATE

BEXIMCO PHARMACEUTICALS LIMITED

TONGI - 1711, GAZIPUR, BANGLADESH

GUIDELINE

GUIDELINE NO.: G-RD-002/00

DEPARTMENT: RESEARCH AND DEVELOPMENT

PAGE NO.: 2 OF 6

TITLE: DRUG-EXCIPIENT COMPATIBILITY STUDIES

EFFECTIVE DATE: 15/07/2014

REVIEW DATE: 14/07/2016

6.0

PRECAUTIONS
Not Applicable

7.0

PROCEDURE
7.1

To conduct Drug-Excipient Compatibility Studies, following steps shall be followed:

1
2
3
4

7.2.1

Choice of Excipients
Preparation of Drug-Excipient Sample
Nature of Container-closure and Selection of Study Conditions
Frequency of Testing and Testing Methodology

Choice of excipients

7.2.1.1 Excipients shall be selected initially on the basis of their functionality, intended
manufacturing process and desired delivery characteristics of dosage form, widespread
pharmaceutical use and commercial availability. The physicochemical properties,
knowledge of potential mechanism of degradation of drug substances and the
composition information of reference products, if any are also to be considered.
7.2.1.2 The final selection of excipients shall be done on the basis of stability testing of one or
more target formulations.
7.2.2

Preparation of drug-excipient sample

7.2.2.1

In the drug-excipient compatibility testing program, binary (1:1 or customized)

powder mixes shall be prepared by mixing drug with the individual excipient by
suitable means or justified. These powder samples shall be made with or without
added water and if required shall be compacted or prepared as slurries.
NAME

DESIGNATION

Abedah Nawreen

Sr. Officer, R&D

Suranjit Dhar

Deputy Manager, R&D

Afroza Akter

Sr. Asst. Manager, Quality (R&D)

Subodh Chandra Das

General Manager, R&D

PREPARED BY

CHECKED BY

APPROVED BY

FRM No.: FRD/098-00

SIGN & DATE

BEXIMCO PHARMACEUTICALS LIMITED

TONGI - 1711, GAZIPUR, BANGLADESH

GUIDELINE

GUIDELINE NO.: G-RD-002/00

DEPARTMENT: RESEARCH AND DEVELOPMENT

PAGE NO.: 3 OF 6

TITLE: DRUG-EXCIPIENT COMPATIBILITY STUDIES

EFFECTIVE DATE: 15/07/2014

REVIEW DATE: 14/07/2016

7.2.2.2

Sample preparation procedure

7.2.2.2.1 Weighed amount of drug substance and excipient shall be placed a suitable pastlemortar or in a glass beaker or in a polyethylene bag and mix thoroughly or any
suitable means.
7.2.2.2.2 Distribute the powder mix in glass vials as per the study plan.
7.2.2.2.3 Close the vial tightly and introduce perforation as required. Perforation should be
adequate to penetrate moisture.
7.2.2.2.4 Drug-excipient blends quantity shall be decided in consideration to the analysis
requirement.
7.2.2.3

Nature of Container-closure and Selection of Study Conditions

7.2.2.3.1 Type A clear glass vial or amber glass vial (if the drug is not stable in light).
7.2.2.4

Labeling

7.2.2.4.1 Each sample vial shall be labeled appropriately.

7.2.2.5

Selection of study conditions

7.2.2.5.1 Compatibility study samples shall be exposed at accelerated temperature and

humidity condition of 40 2C and 75 5% RH.

NAME

DESIGNATION

Abedah Nawreen

Sr. Officer, R&D

Suranjit Dhar

Deputy Manager, R&D

Afroza Akter

Sr. Asst. Manager, Quality (R&D)

Subodh Chandra Das

General Manager, R&D

PREPARED BY

CHECKED BY

APPROVED BY

FRM No.: FRD/098-00

SIGN & DATE

BEXIMCO PHARMACEUTICALS LIMITED

TONGI - 1711, GAZIPUR, BANGLADESH

GUIDELINE

GUIDELINE NO.: G-RD-002/00

DEPARTMENT: RESEARCH AND DEVELOPMENT

PAGE NO.: 4 OF 6

TITLE: DRUG-EXCIPIENT COMPATIBILITY STUDIES

EFFECTIVE DATE: 15/07/2014

REVIEW DATE: 14/07/2016

7.2.2.5.2 Compatibility study samples shall be exposed at room condition i.e. temperature and
humidity of 25 2C and 60 5% RH.
7.2.2.5.3 For thermo labile drug substances or excipient, study conditions shall be lower than
the above mentioned conditions. Accelerated temperature and humidity condition
may be of 25 2C and 60 5% RH and Fridge condition (2 8 oC) may be
considered as the room condition.
7.2.2.6

Frequency of Testing and Testing Methodology

7.2.2.6.1 Duplicate samples of drug-excipient blends are analyzed at the Initial (Stage 0), then
after 4 week or as required.
7.2.2.6.2 The following testing frequency should be followed:
Frequency
0 and 4 weeks

Condition
Accelerated,
402C/755%RH
40C/50C
Room condition,
252C/605%RH
2-8C

0 and 4 weeks

N
N

P/N*

0 and 4 weeks

0 and 4 weeks

Tests
Appearance, Assay and
Impurities (as applicable)
Appearance, Assay and
Impurities (as applicable)
Appearance, Assay and
Impurities (as applicable)
Appearance, Assay and
Impurities (as applicable)

P- Perforated sample, N- Non Perforated sample

*- Non perforated sample at accelerated condition can be incubated in suitable alternate also
like 40C/50C (dryer) or 40C/25% RH.

NAME

DESIGNATION

Abedah Nawreen

Sr. Officer, R&D

Suranjit Dhar

Deputy Manager, R&D

Afroza Akter

Sr. Asst. Manager, Quality (R&D)

Subodh Chandra Das

General Manager, R&D

PREPARED BY

CHECKED BY

APPROVED BY

FRM No.: FRD/098-00

SIGN & DATE

BEXIMCO PHARMACEUTICALS LIMITED

TONGI - 1711, GAZIPUR, BANGLADESH

GUIDELINE

GUIDELINE NO.: G-RD-002/00

DEPARTMENT: RESEARCH AND DEVELOPMENT

PAGE NO.: 5 OF 6

TITLE: DRUG-EXCIPIENT COMPATIBILITY STUDIES

EFFECTIVE DATE: 15/07/2014

REVIEW DATE: 14/07/2016

8.0

9.0

7.2.3

Compatibility Testing Methods

7.2.3.1

Physical stability shall be measured by visual or microscopic observation on

appearance, to see any color change or Hygroscopicity or deliquescent behavior.

7.2.3.2

Chemical stability shall be measured by chromatographic method.

REFERENCES
8.1

ICH Guideline of Stability testing of New Drug Substances and Products Q1A (R2).

8.2

ICH Guideline of Pharmaceutical Development Q8 (R2).

REVISION HISTORY
Sl.
No.
01

Revision
Status
00

Details of Revision

Issue No.
First issue

Effective Remarks
Date
15/07/2014 Training
required

10.0 APPENDICES
Not Applicable

NAME

DESIGNATION

Abedah Nawreen

Sr. Officer, R&D

Suranjit Dhar

Deputy Manager, R&D

Afroza Akter

Sr. Asst. Manager, Quality (R&D)

Subodh Chandra Das

General Manager, R&D

PREPARED BY

CHECKED BY

APPROVED BY

FRM No.: FRD/098-00

SIGN & DATE

BEXIMCO PHARMACEUTICALS LIMITED

TONGI - 1711, GAZIPUR, BANGLADESH

GUIDELINE

GUIDELINE NO.: G-RD-002/00

DEPARTMENT: RESEARCH AND DEVELOPMENT

PAGE NO.: 6 OF 6

TITLE: DRUG-EXCIPIENT COMPATIBILITY STUDIES

EFFECTIVE DATE: 15/07/2014

REVIEW DATE: 14/07/2016

11.0 DISTRIBUTION LIST

Distribution List of Guideline
Department
Serial No. of Copy Number of Copies
Research & Development

01

01

NAME

DESIGNATION

Abedah Nawreen

Sr. Officer, R&D

Suranjit Dhar

Deputy Manager, R&D

Afroza Akter

Sr. Asst. Manager, Quality (R&D)

Subodh Chandra Das

General Manager, R&D

PREPARED BY

CHECKED BY

APPROVED BY

FRM No.: FRD/098-00

Remarks

SIGN & DATE