Table 1.
Methods to prevent lipid peroxidation and maintain or improve oxidative stability in pharmaceutical emulsions.
| Approach | Method/Include | Action/Property | Effect |
|---|---|---|---|
| Content based | Vitamin C (ascorbic acid), Vitamin E (α-tocopherol), propyl gallate, ascorbyl palmitate | Antioxidant at air or water interfaces | Maximise/improve oxidative stability, retards oxidation |
| Oleic acid | Antioxidant | Reduce oxidation | |
| β-carotene, butylated hydroxy toluenes (BHT) and butylated hydroxyanisole (BHA) | Encapsulate drug and unsaturated fatty acid chains | Provide protection against oxidation | |
| Lecithin | Emulsifier, stabiliser, dispersing agent | Reduce interfacial tension, form thick and viscoelastic membranes around lipid droplets, synergistic with other natural antioxidants | |
| Saturated medium chain triglycerides (MCT) | Good solubility | Resistant to peroxidation | |
| Mono-unsaturated fatty acids | Less prone to peroxidation compared to di- or poly-unsaturated fatty acids | Reduce oxidation | |
| Sphingolipid | Avoid aggregation and content leakage caused by oxidation and hydrolysis of phospholipids | Maintain formulation stability preventing further oxidative damage | |
| Thioglycolic acid (oil soluble) | Oxidative inhibitor | Inhibit oxidative degradation of certain drugs – maintaining stability | |
| Silica particles | Stabiliser | Improve long term physical stability | |
| Poloxamer–chitosan | As emulgating film | Maintain droplet diameter – stabilising castor oil-based nano-sized emulsion | |
| Hydrophilic polymers (poloxamer, pluronic) | Stabiliser | Provide stability for emulsions | |
| Metal chelators deferoxamine (DFO) and ethylenediaminetetraacetic acid (EDTA) | Metal binding | Reduce lipid peroxidation | |
| Preservatives | Prevent growth of harmful bacteria, yeast and mould | May provide certain protection against oxidation | |
| Surfactants with antioxidant property | Coat droplets | May reduce surfaces available for oxidation thus preventing oxidation interactions | |
| Preparation based | Reduce or remove trace metals | Initiate and propagate peroxidation | Reduce oxidation reactions |
| Alteration to surfactants' and stabilisers' concentrations (in general) | Decrease droplet/particle size | Increase oxidative stability | |
| Use highly pure and refined ingredients | Free from pigments, decomposition products, sterols, free hydrocarbons and peroxides | Reduce contaminating agents | |
| Nitrogen atmosphere | Create controlled environment | Protect oxidation prone components | |
| Protection from light | Create controlled environment | Protect emulsions | |
| Packaging in inert atmosphere | Create controlled environment | Eliminate oxidation prone contaminants | |
| Monitoring pH levels during formulation and storage | Antioxidant effects | Control factors (electrochemical, pH) that effect the actions of antioxidants |