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