I recently received a call from a surgery center asking why some epidural steroid injections (ESIs) are a clear solution and why some are a milky suspension. Additionally, the caller wanted to know if the clear solutions have a different effect than milky suspensions.
All drugs or chemicals have various degrees of solubility based on their chemical structure. Some chemicals dissolve very easily in water and some are completely insoluble. For example, betamethasone sodium phosphate is freely soluble in water while betamethasone acetate is relatively insoluble in water. When looking at a vial of betamethasone sodium phosphate it is a clear, colorless solution. However, when looking at a vial of betamethasone sodium phosphate combined with betamethasone acetate the product looks milky and must be shaken to redistribute the chemical. In this case, betamethasone acetate is not dissolved in water but is a milky suspension.
Since our bodies are made up mostly of water, chemicals react very much the same way when injected into our bodies as they do when mixed with water. This means that a soluble drug like betamethasone sodium phosphate is absorbed easily and at a much faster rate than a drug like betamethasone acetate. Therefore, when these two drugs are combined together and injected into the epidural space, the end result is a very quick absorption and biological effect from the betamethasone sodium phosphate and a longer, sustained action from the slower absorbing betamethasone acetate.
Another popular ESI that is water soluble (clear) is dexamethasone sodium phosphate. Non-soluble (milky) suspensions include triamcinolone acetonide and methylprednisolone acetate. Both of these products must be shaken before injection.
To summarize the answer to the caller, I told them it is simply a matter of water solubility. A soluble drug is a solution that once injected, usually has a quicker onset, but is shorter acting. An insoluble drug is a suspension, usually with a slower onset, but is longer acting. A combination drug will have benefits of both.
Next week we will discuss the difference between preserved and presevative-free ESIs and the safety implications of each.