13.1.1 In aqueous solution
On reconstitution, dry powder medicines are relatively unstable in aqueous vehicles and normally degrade by hydrolysis (decomposition of a substance by a chemical reaction with water). This reaction may be accelerated by a change in pH, resulting either from the diluent or from a second medicine. Such degradation may be minimised and prevented by using the recommended diluent, e.g. erythromycin must be reconstituted with water for injections because it will not dissolve in sodium chloride 0.9% or glucose 5%. After it has been dissolved it should be diluted in sodium chloride 0.9% and not glucose 5% because it degrades at an acidic pH. Alternatively sodium bicarbonate may be added to a glucose 5% bag to ensure the pH is in the range at which erythromycin is stable. See the monograph for erythromycin in Section B for further details.
Photodegradation is the breakdown of a substance by light. It occurs to a significant degree in a small number of medicines, e.g. sodium nitroprusside. Degradation is usually the result of ultraviolet (UV) light, which is found in daylight but not artificial fluorescent light, although sodium nitroprusside is rapidly degraded by both fluorescent and UV light.
Photodegradation of some other light-sensitive medicines (e.g. ciprofloxacin or furosemide) is not clinically important provided that direct exposure to strong daylight or sunlight is avoided. Intravenous nutrition should be light protected as some vitamins are light sensitive.
Precipitated medicines are pharmacologically inactive but hazardous to the patient. Precipitates can block catheters and damage capillaries and may lead to coronary and pulmonary emboli. The injection of medicine precipitates must therefore be avoided.
13.2.1 Causes of precipitation
The most likely reason for precipitation is the mixing in the infusion container or the infusion line of two medicines with very different pH values, especially if one is acidic and the other alkaline.
This occurs most commonly from the mixing of organic anions (ions with a negative charge) and cations (ions with a positive charge), which join together to form ion pairs. Gentamicin and other aminoglycosides are incompatible with heparin, penicillins and cephalosporins because of this. It is essential to avoid these interactions. Medicines that could form an ion pair should never be allowed to mix in an infusion container, syringe or administration line. Flushing between the administration of different medicines helps avoid such interactions (see Section A8 for further details).