Standard Operating Procedure for Addition Sequence of Ingredients in Elixir Manufacturing
| Department | Elixir Department |
|---|---|
| SOP No. | SOP/ELX/053/2025 |
| Supersedes | SOP/ELX/053/2022 |
| Page No. | Page 1 of 8 |
| Issue Date | 11/04/2025 |
| Effective Date | 15/04/2025 |
| Review Date | 11/04/2026 |
1. Purpose
To define the procedure for the correct sequence of addition of ingredients during elixir manufacturing to ensure proper mixing, product stability, and compliance with batch manufacturing instructions.
2. Scope
This SOP applies to all personnel involved in the addition of ingredients during the manufacturing of elixirs in the Elixir Department, including APIs, excipients, solvents, and additives.
3. Responsibilities
- Manufacturing Operator:
- Add ingredients as per the defined sequence in the BMR.
- Ensure proper mixing after each addition.
- Production Supervisor:
- Verify each addition and sign the BMR.
- QA Officer:
- Perform in-process checks and ensure the sequence is followed as per procedure.
4. Accountability
The Production Head is accountable for ensuring all ingredients are added in the correct order and documented appropriately.
5. Procedure
5.1 General Guidelines
- Refer to the BMR for the prescribed sequence of
addition for each batch.
Ensure the manufacturing tank is prepared and clean as per SOP/ELX/051/2025.
Use only verified and approved materials, with container and label checked prior to addition.
5.2 Typical Order of Addition
- Vehicle/Base Solvent: Add the main diluent (e.g., purified water, propylene glycol).
- Preservatives: Add dissolved preservatives such as sodium benzoate or methylparaben under stirring.
- Sweeteners: Add bulk sweeteners (sucrose/sorbitol) or intense sweeteners (aspartame/sucralose) in solution form.
- Active Ingredient: Slowly add API under continuous stirring to ensure uniform dispersion or dissolution.
- Buffering Agents: Add buffers such as citric acid or sodium citrate after the API is fully dissolved.
- Colorants and Flavors: Add permitted color solutions and flavors in the final phase after cooling (if applicable).
- Volume Adjustment: Adjust final volume using purified water after verifying homogeneity and pH.
5.3 Precautions During Addition
- Maintain constant stirring during and after each addition to ensure even distribution.
- Record the time of each addition in the BMR.
- Allow sufficient time between additions for complete dissolution or dispersion of each ingredient.
- For heat-sensitive or volatile ingredients (e.g., ethanol or flavors), add after cooling the batch to room temperature.
5.4 Documentation
- Enter the addition time, material name, batch number, and quantity in the Ingredient Addition Log (Annexure-1).
- Get verification signatures from the supervisor and QA (if required).
6. Abbreviations
- BMR: Batch Manufacturing Record
- SOP: Standard Operating Procedure
- API: Active Pharmaceutical Ingredient
- QA: Quality Assurance
7. Documents
- Ingredient Addition Log (Annexure-1)
- Batch Manufacturing Record (BMR)
- Sequence Verification Checklist (Annexure-2)
8. References
- ICH Q8 – Pharmaceutical Development
- WHO TRS 970 Annex 2 – GMP Guidelines for Liquid Dosage Forms
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Ingredient Addition Log
| Date | Material Name | Batch No. | Quantity Added | Time | Added By | Verified By |
|---|---|---|---|---|---|---|
| 11/04/2025 | Sodium Benzoate | SB2025 | 0.500 kg | 10:15 AM | Rajesh Kumar | Sunita Reddy |
Annexure-2: Sequence Verification Checklist
| Step | Ingredient | Order Correct (Yes/No) | Verified By |
|---|---|---|---|
| 1 | Purified Water | Yes | Sunita Reddy |
| 2 | Sodium Benzoate | Yes | Sunita Reddy |
| 3 | Sorbitol Solution | Yes | Sunita Reddy |
Revision History:
| Revision Date | Revision No. | Revision Details | Reason for Revision | Approved By |
|---|---|---|---|---|
| 01/01/2024 | 1.0 | Initial Issue | New SOP | QA Head |
| 11/04/2025 | 2.0 | Included Verification Checklist | Process Control Enhancement | QA Head |