Pharmaceutical liquid preparation is a critical formulation. Here a lot of factors need to be considered for product quality and stablility. Here we try o focus on few points, which are critical for such type of formulation.


Particle Size

Partcile size is an important parameter for pharmaceutical liquid preparation. Pparticle size can affect the rate a substance will dissolve. Smaller particles have a larger surface area, therefore making dissolution occur more quickly. 


 Preservative acting pH:

  • Methyl Paraben: 4.0 to 8.0
  • Propyl Paraben: 4.0 to 8.0
  • Benzalkonium chloride: 4.0 to 10.0
  • Sodium Benzoate: < 5.0
  • Benzoic Acid: < 5.0
  • Chlorobutanol: < 5.50


Few solution/syrup preparation process:

1. Syrup preparation:

- Liquid Sorbitol mix with Glycerin (glycerol), Sucrose (if needed) mix with Purified water.


2. Methyl Paraben and Propyl Paraben Solution: 

- Methyl Paraben and Propyl Paraben can be dissolved in presence of Glycerol or Propylene glycol.


3. Menthol Solution:

- Menthol is mixed with Ethanol.


4. Benzoic acid solution:

- Soluble in ethanol and water. Aqueous solubility of benzoic acid may be enhanced by the addition of citric acid or sodium acetate to the solution.


5. Aspartame solution:

- Slightly soluble in ethanol (95%); sparingly soluble in water. Solubility increases at higher temperature and at more acidic pH.


Common range of Methyl Paraben and Propyl Paraben in Oral solution preparation:

- Methyl Paraben: 0.015-0.2% 

- Propyl Paraben: 0.01-0.02%


Cause of Propyl Paraben and Propylene Glycol in combination with Methyl Paraben

- Propyl Paraben (0.01-0.02%) show synergistic effect and Propylene glycol (2-5%) improve the preservative efficacy.


Co-solvents are commonly used in oral solution preparation

- Propylene glycol, Glycerol, Ethanol, PEG.


Common buffer salts used in oral solution preparation

- Acetates (acetic acid, sodium acetate), 1-2%

- Citrates (citric acid, sodium citrate), 1-5%

- Phosphates (sodium phosphate, disodium phosphate), 0.8-2%


Antioxidants are commonly used for aqueous and oil bases solution preparation

- For aqueous solution: Sodium sulfite, Sodium metabisulfite, Sodium formaldehyde sulfoxylate, and Ascorbic acid.

- For oil base solution: Butylated Hydroxytoluene (BHT), Butylated Hydroxyanisole (BHA), and Propyl Gallate.

- Typically antioxidants are employed in low concentrations (< 0.2% w/w).