SOP for Drug-Excipient Compatibility Studies

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.

SCOPE

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

RESPONSIBILITY

• Authorized users are responsible for carrying out the procedure.
• Asst. Manager/ Sr. Asst. Manager/ and Deputy Manager, R&D or his/her nominee is responsible for training and implementation.

ACCOUNTABILITY

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

PROCEDURE

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

1. Choice of Excipients
2. Preparation of Drug-Excipient Sample
3. Nature of Container-closure and Selection of Study Conditions
4. Frequency of Testing and Testing Methodology

Choice of Excipients

• 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.
• The final selection of excipients shall be done on the basis of stability testing of one or more target formulations.

Preparation of Drug-Excipient sample

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.

Sample Preparation Procedure

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

ALSO READ: Pre-formulation and Formulation Development

Nature of Container-closure and Selection of Study Conditions

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

Labeling

• Each sample vial shall be labeled appropriately.

Selection of Study Conditions

• Compatibility study samples shall be exposed at accelerated temperature and humidity condition of 40 ± 2°C and 75 ± 5% RH.
• Compatibility study samples shall be exposed at room condition i.e. temperature and humidity of 25 ±2°C and 60 ± 5% RH.
• 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 ± 2°C and 60 ± 5% RH and Fridge condition (2 – 8°C) may be considered as the room condition.

Frequency of Testing and Testing Methodology

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

	Condition	Frequency	Tests
P/N*	Accelerated, 40±2°C/75±5%RH	0 and 4 weeks	Appearance, Assay and Impurities (as applicable)
N	40°C/50°C	0 and 4 weeks	Appearance, Assay and Impurities (as applicable)
N	Room condition, 25±2°C/60±5%RH	0 and 4 weeks	Appearance, Assay and Impurities (as applicable)
N	2-8°C	0 and 4 weeks	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 40°C/50°C (dryer) or 40°C/25% RH.

Compatibility Testing Methods

• Physical stability shall be measured by visual or microscopic observation on appearance, to see any color change or Hygroscopicity or deliquescent behavior.
• Chemical stability shall be measured by chromatographic method.

REFERENCES

1. ICH Guideline of Stability testing of New Drug Substances and Products Q1A (R2).
2. ICH Guideline of Pharmaceutical Development Q8 (R2).

ANNEXURE

Nil

ABBREVIATIONS

R&D: Research and Development

API: Active Pharmaceutical Ingredient

RH: Relative Humidity

REVISION HISTORY

Nil

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