cyclodextrins, or particle size reduction.

Record the chosen method in the batch manufacturing record (BMR) and ensure it is pharmaceutically acceptable for nasal formulations.

4.1.2 Weighing of Ingredients

• Weigh the required amounts of APIs and excipients using a calibrated balance. Record the weights in the BMR, ensuring they fall within the acceptable range (±2% of target weight).
• Transfer the weighed materials into a sterile mixing vessel for further processing.

4.2 Solubility Enhancement Techniques

4.2.1 pH Adjustment

• If pH adjustment is the chosen method, dissolve the active ingredient in water or buffer solution and adjust the pH using a suitable acid or base (e.g., HCl or NaOH). The target pH range should be recorded in the BMR.
• Use a calibrated pH meter to ensure that the final pH is within the desired range (e.g., 5.0-7.0 for nasal formulations). Record the pH in the pH adjustment log.

4.2.2 Use of Co-Solvents or Surfactants

• For poorly soluble drugs, incorporate co-solvents (e.g., ethanol, glycerin) or surfactants (e.g., polysorbates) to enhance solubility. Add the solubilizing agents slowly while stirring the formulation to ensure uniform distribution.
• Mix the solution using a mechanical stirrer or homogenizer. Record the mixing speed and time in the BMR.

4.2.3 Particle Size Reduction

• For drugs that require particle size reduction, use micronization or nanonization techniques to achieve the desired particle size (typically 1-5 microns for nasal formulations).
• After processing, test the particle size using a laser diffraction analyzer or dynamic light scattering. Document the results in the particle size testing log.

4.3 Quality Control Testing

4.3.1 Solubility Testing

• Test the solubility of the drug in the final formulation using validated analytical methods (e.g., UV spectrophotometry or HPLC).
• Document the solubility test results in the solubility testing log, ensuring the drug is fully dissolved or uniformly dispersed.

4.3.2 Homogeneity Testing

• Test the homogeneity of the formulation by sampling from different areas of the mixing vessel. Ensure uniform distribution of the solubilized drug using HPLC or UV spectrophotometry.
• Record the results in the homogeneity testing log, ensuring the drug concentration across samples does not deviate by more than 2%.

4.4 Stability Testing

4.4.1 Long-Term Stability Testing

• Store samples under controlled environmental conditions (e.g., 25°C, 60% RH) and test them at 1-month, 3-month, and 6-month intervals.
• Test for physical changes (e.g., precipitation, color changes) and chemical stability (e.g., drug concentration, pH). Record the results in the stability testing log.

4.4.2 Accelerated Stability Testing

• Perform accelerated stability testing by storing the formulation at elevated temperatures (e.g., 40°C, 75% RH) to predict its shelf life. Test at regular intervals to evaluate stability.
• Document the results in the stability testing log and adjust the product expiration date if necessary.

4.5 Documentation

• Document all steps of the solubility enhancement process, including ingredient weights, mixing times, pH adjustments, and testing results in the batch manufacturing record (BMR).
• Ensure all quality control tests, including solubility, homogeneity, and stability, are recorded in the appropriate logs. QA personnel must review and sign off before the product is released.

4.6 Equipment Cleaning and Calibration

• Clean and sterilize all equipment used in the solubility enhancement process, including stirrers, homogenizers, and particle size analyzers, according to the cleaning validation protocol.
• Calibrate the equipment according to the calibration schedule, and record the results in the cleaning and calibration logs.

5) Abbreviations, if any

• API: Active Pharmaceutical Ingredient
• QA: Quality Assurance
• HPLC: High-Performance Liquid Chromatography
• BMR: Batch Manufacturing Record

6) Documents, if any

• Batch Manufacturing Record (BMR)
• Solubility Testing Log
• Homogeneity Testing Log
• Particle Size Testing Log
• Stability Testing Log
• Cleaning Log
• Calibration Log

7) References, if any

• ICH Q1A – Stability Testing Guidelines
• FDA Guidance on Solubility Enhancement for Drug Products

8) SOP Version

Version 1.0

Annexure

1. Solubility Testing Log Template

Date	Formulation	Solubility Test Method	Solubility Results	Operator Initials	QA Approval
DD/MM/YYYY	Formulation Name	Test Method	Results	Operator Name	QA Name

2. Particle Size Testing Log Template

Date	Formulation	Particle Size (µm)	Test Method	Operator Initials	QA Approval
DD/MM/YYYY	Formulation Name	Size	Method	Operator Name	QA Name

3. Homogeneity Testing Log Template

Date	Formulation	Test Point (Top/Middle/Bottom)	Drug Concentration (%)	Operator Initials	QA Approval
DD/MM/YYYY	Formulation Name	Test Point	Concentration	Operator Name	QA Name

4. Stability Testing Log Template

Date	Formulation	Storage Conditions	Time Interval	Stability Results	Operator Initials	QA Approval
DD/MM/YYYY	Formulation Name	Temperature and Humidity	1 month, 3 months, etc.	Pass/Fail	Operator Name	QA Name

5. Cleaning and Calibration Log Template

Date	Equipment ID	Cleaning/Calibration Procedure	Operator Initials	QA Approval
DD/MM/YYYY	Equipment Name/ID	Procedure	Operator Name	QA Name