Standard Operating Procedure for Solubility Profiling of Active Ingredients in Elixir Formulations
| Department | Elixir Department |
|---|---|
| SOP No. | SOP/ELX/050/2025 |
| Supersedes | SOP/ELX/050/2022 |
| Page No. | Page 1 of 8 |
| Issue Date | 11/04/2025 |
| Effective Date | 15/04/2025 |
| Review Date | 11/04/2026 |
1. Purpose
To outline the procedure for conducting solubility profiling of active pharmaceutical ingredients (APIs) in various solvents and co-solvent systems during elixir formulation development to aid in selection of suitable solubilizing agents.
2. Scope
This SOP is applicable to formulation and analytical development teams performing solubility profiling of APIs for elixir dosage forms in the Elixir Department. It includes solubility assessment in purified water, alcohols, glycols, surfactants, and buffer systems.
3. Responsibilities
- Formulation Scientist:
- Design and perform solubility studies as per protocol.
- Analytical Scientist:
- Analyze solubility samples using validated analytical methods.
- QA Officer:
- Review protocols, results, and ensure compliance with applicable regulatory standards.
4. Accountability
The R&D Head is accountable for ensuring that solubility profiling is conducted using scientifically sound and validated approaches prior to formulation development.
5. Procedure
5.1 Preparation
- Ensure
all reagents and solvents (e.g., water, ethanol, propylene glycol) are of analytical grade and documented in the study plan.
Label all glassware and containers clearly and maintain controlled temperature during the study (25°C ± 2°C unless otherwise specified).
5.2 Selection of Solvents
- Shortlist solvents and co-solvents based on:
- Regulatory acceptability (as per IIG database, GRAS status)
- Chemical compatibility with the API
- Formulation requirement (oral liquid)
5.3 Solubility Determination Procedure
- Weigh excess API (approx. 100 mg) into screw-capped vials.
- Add 10 mL of each solvent to separate vials.
- Stir at 25°C for 24 hours using magnetic stirrers or shaking water bath.
- Visually inspect and note clear/unclear solutions.
- Centrifuge or filter through 0.45 µm membrane filter.
- Quantify drug concentration in the supernatant using UV or HPLC method.
5.4 Expression of Solubility
- Express solubility in terms of:
- mg/mL
- Parts of solvent required to dissolve 1 part of solute
- Classify solubility as per USP/NF:
- Very soluble: <1 part solvent
- Freely soluble: 1–10 parts
- Sparingly soluble: 30–100 parts
- Practically insoluble: >10,000 parts
5.5 Reporting
- Document findings in the Solubility Profiling Report (Annexure-1).
- Prepare comparison table (Annexure-2) and attach instrument data sheets.
- QA to verify and archive final report before proceeding to formulation screening.
6. Abbreviations
- SOP: Standard Operating Procedure
- API: Active Pharmaceutical Ingredient
- QA: Quality Assurance
- USP: United States Pharmacopeia
- GRAS: Generally Recognized As Safe
7. Documents
- Solubility Profiling Report (Annexure-1)
- Solubility Comparison Table (Annexure-2)
- Instrument Calibration Records (Annexure-3)
8. References
- ICH Q8 – Pharmaceutical Development
- USP General Chapter <1230> – Solubility Classification
- FDA Inactive Ingredient Database
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Solubility Profiling Report
| API Name | Solvent | Temp (°C) | Solubility (mg/mL) | USP Class | Remarks |
|---|---|---|---|---|---|
| Drug A | Propylene Glycol | 25 | 85.6 | Freely Soluble | Suitable for use |
| Drug A | Water | 25 | 4.3 | Sparingly Soluble | Requires co-solvent |
Annexure-2: Solubility Comparison Table
| Solvent | Solubility (mg/mL) | Classification |
|---|---|---|
| Water | 4.3 | Sparingly Soluble |
| Ethanol | 56.1 | Freely Soluble |
| PG | 85.6 | Freely Soluble |
Annexure-3: Instrument Calibration Records
| Instrument | Calibration Date | Next Due Date | Performed By |
|---|---|---|---|
| UV Spectrophotometer | 01/04/2025 | 01/10/2025 | Ajay Mehta |
| Analytical Balance | 01/04/2025 | 01/07/2025 | Manju Sharma |
Revision History:
| Revision Date | Revision No. | Revision Details | Reason for Revision | Approved By |
|---|---|---|---|---|
| 01/01/2024 | 1.0 | Initial Version | New SOP | QA Head |
| 11/04/2025 | 2.0 | Added Annexures and Solvent Classification Tables | Process Standardization | QA Head |