Despite their widespread use for anesthesia and sedation, propofol emulsions have several unresolved issues, including pain on injection, stability concerns, and propensity to support bacterial growth. Pain accompanying a propofol injection has been attributed to the amount of free as opposed to emulsified propofol in the blood, which can differ with the formulation. Emulsions are inherently unstable and subject to several types of destabilization, but the actual mechanism may vary between formulations or batches. Free drug concentration and emulsion stability have not been widely studied between batches of propofol emulsions. Verifying whether batch-to-batch variability is a contributing factor to pain on injection or emulsion destabilization will help us better assess the causes and guide the design of future propofol formulations. METHODS: Several samples of generic 1% propofol emulsion from various batches were compared. Free drug concentration was measured using an equilibrium dialysis method. Emulsion stability was evaluated by visible observation and by measuring droplet size distribution and polydispersity during shelf storage for up to 21 months. RESULTS: Small differences in free drug concentration were observed between samples (10.6-16.7 μg/mL), but these differences were not statistically significant (p > 0.05). Emulsion droplet size (235.4-221.1 nm) and polydispersity (0.115-0.095) did not differ statistically over 21 months of storage. All batches were resistant to creaming and other destabilization mechanisms. CONCLUSIONS: Batch-to-batch variability does not significantly alter the free drug concentration or stability of propofol formulations. If pain on injection of propofol is in fact related to the free propofol drug concentration, then it is unlikely that batch-to-batch variability causes any changes in pain on propofol injection.
Despite their widespread use for anesthesia and sedation, propofol emulsions have several unresolved issues, including pain on injection, stability concerns, and propensity to support bacterial growth. Pain accompanying a propofol injection has been attributed to the amount of free as opposed to emulsified propofol in the blood, which can differ with the formulation. Emulsions are inherently unstable and subject to several types of destabilization, but the actual mechanism may vary between formulations or batches. Free drug concentration and emulsion stability have not been widely studied between batches of propofol emulsions. Verifying whether batch-to-batch variability is a contributing factor to pain on injection or emulsion destabilization will help us better assess the causes and guide the design of future propofol formulations. METHODS: Several samples of generic 1% propofol emulsion from various batches were compared. Free drug concentration was measured using an equilibrium dialysis method. Emulsion stability was evaluated by visible observation and by measuring droplet size distribution and polydispersity during shelf storage for up to 21 months. RESULTS: Small differences in free drug concentration were observed between samples (10.6-16.7 μg/mL), but these differences were not statistically significant (p > 0.05). Emulsion droplet size (235.4-221.1 nm) and polydispersity (0.115-0.095) did not differ statistically over 21 months of storage. All batches were resistant to creaming and other destabilization mechanisms. CONCLUSIONS: Batch-to-batch variability does not significantly alter the free drug concentration or stability of propofol formulations. If pain on injection of propofol is in fact related to the free propofol drug concentration, then it is unlikely that batch-to-batch variability causes any changes in pain on propofol injection.
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Keywords:
batches; emulsion destabilization; emulsions; pain on injection; propofol