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).
