SOP for Weighing and Dispensing of Lipid and Aqueous Components

Weighing and Dispensing of Lipid and Aqueous Components for Liposome and Emulsion Formulations

1) Purpose

The purpose of this SOP is to describe the procedure for the accurate weighing and dispensing of lipid and aqueous components used in the formulation of liposomes and emulsions. Proper weighing and dispensing are crucial for maintaining consistency and ensuring that the final formulation meets the desired specifications.

2) Scope

This SOP applies to all operators and technicians involved in the preparation of lipid and aqueous components for liposome and emulsion formulations in both research and production settings. The procedure ensures that components are measured precisely and dispensed correctly to achieve the proper lipid-to-aqueous phase ratio.

3) Responsibilities

Operators: Responsible for the accurate weighing and dispensing of lipid and aqueous components as per this SOP. They must also ensure that the equipment used is calibrated and that the process is documented properly.
QA Team: Responsible for verifying the weights and volumes of components used in formulations and ensuring that records are accurately maintained.
QC Team: Responsible for testing the quality of the weighed and dispensed components to ensure that they meet the required specifications before use in production.

4) Procedure

4.1 Equipment Setup

Before beginning the weighing

and dispensing process, ensure that all equipment is cleaned, sterilized, and calibrated to ensure accurate measurements.

4.1.1 Required Equipment

Analytical balance (with sensitivity of at least 0.0001 g for lipid components)
Glass beakers and volumetric flasks (for aqueous components)
Calibrated pipettes (for precise liquid measurement)
Stainless steel spatulas (for handling lipid powders)
Calibrated syringes (for solvent and small-volume dispensing)

4.1.2 Equipment Calibration

Ensure that the equipment is properly calibrated and that all calibration records are up-to-date:

4.1.2.1 Calibrate the analytical balance using certified calibration weights. Record the calibration details in the equipment logbook.
4.1.2.2 Ensure pipettes and syringes are calibrated and adjusted for accurate liquid measurement.
4.1.2.3 Verify that volumetric flasks are clean, dry, and free of any residue before use.

4.2 Weighing of Lipid Components

Accurate weighing of lipid components is critical for achieving the correct lipid-to-aqueous phase ratio in liposome and emulsion formulations. The following steps outline the procedure for weighing lipids:

4.2.1 Weighing Procedure

4.2.1.1 Tare the analytical balance before placing the lipid component onto the balance to ensure accurate measurement.
4.2.1.2 Carefully weigh the lipid component (e.g., phospholipids, cholesterol) as per the formulation specifications in the Batch Manufacturing Record (BMR).
4.2.1.3 Handle lipid powders with stainless steel spatulas, ensuring that no material is lost during transfer. For liquids, use calibrated pipettes or syringes for precise measurement.
4.2.1.4 Record the weight of each lipid component in the BMR and verify that the weight is within acceptable tolerance limits.
4.2.1.5 Store the weighed lipids in clean, labeled containers until they are ready for use in the formulation process.

4.2.2 Handling Precautions

Since many lipids are hygroscopic or sensitive to oxidation, proper handling is essential:

4.2.2.1 Weigh lipid components in a low-humidity environment to prevent moisture absorption.
4.2.2.2 Minimize exposure to air and light by storing weighed lipids in sealed, opaque containers.
4.2.2.3 Use nitrogen-purged containers if lipids are particularly sensitive to oxidation.

4.3 Dispensing of Aqueous Components

Aqueous components, such as buffers or water, must be accurately measured to ensure consistency in the final formulation. The following steps outline the procedure for dispensing aqueous components:

4.3.1 Dispensing Procedure

4.3.1.1 Measure the required volume of the aqueous component using a volumetric flask or calibrated pipette, depending on the volume specified in the formulation.
4.3.1.2 For small volumes, use calibrated syringes or pipettes to ensure precision.
4.3.1.3 Dispense the aqueous component into a clean, labeled container and record the volume in the BMR.
4.3.1.4 Ensure that the aqueous component is maintained at the correct temperature and pH as per the formulation requirements.

4.3.2 Buffer Preparation (if applicable)

If the aqueous component is a buffer, prepare it according to the following steps:

4.3.2.1 Weigh the required buffer salts using an analytical balance, and dissolve them in distilled or deionized water.
4.3.2.2 Adjust the pH of the buffer using a pH meter, adding acid or base as required.
4.3.2.3 Filter the buffer through a 0.22 μm filter to ensure sterility, if necessary.

4.4 Documentation and Record Keeping

Accurate record-keeping is essential to ensure traceability and quality control of lipid and aqueous components used in liposome and emulsion formulations.

4.4.1 Record the weight and volume of each component in the Batch Manufacturing Record (BMR), along with the operator’s initials and the date of weighing or dispensing.
4.4.2 Any deviations from the specified weights or volumes must be documented, and corrective actions should be taken as needed.
4.4.3 Ensure that all containers of weighed or dispensed components are labeled with the material name, batch number, weight or volume, and preparation date.

4.5 Storage of Weighed and Dispensed Components

Once the components have been weighed or dispensed, they must be stored appropriately until use in the formulation:

4.5.1 Store lipid components in airtight containers at the specified temperature (e.g., -20°C for phospholipids) to prevent degradation.
4.5.2 Store aqueous components in sterilized containers, and ensure that they are kept at the required temperature and pH.
4.5.3 All stored materials must be labeled with the material name, batch number, weight or volume, and storage conditions.

5) Abbreviations, if any

BMR: Batch Manufacturing Record
PPE: Personal Protective Equipment

6) Documents, if any

Batch Manufacturing Record (BMR, see Annexure 1)
Equipment Calibration Log

7) References, if any

FDA Guidelines for Liposome Drug Products
International Conference on Harmonisation (ICH) Q7: Good Manufacturing Practice Guide

8) SOP Version

Version 1.0

Annexure

Annexure 1: Batch Manufacturing Record Template


  
    Batch No.
    Material
    Weight/Volume
    Operator Initials
    Date
    QA Signature
  
  
    Batch Number
    Material Name
    Weight in grams / Volume in mL
    Operator Name
    DD/MM/YYYY
    QA Name

Batch No.	Material	Weight/Volume	Operator Initials	Date	QA Signature
Batch Number	Material Name	Weight in grams / Volume in mL	Operator Name	DD/MM/YYYY	QA Name