Macrogol incompatibilities

Benzylpenicillin is incompatible with rubber products and metal ions. Stability is affected by alcohols, surfactants, oxidizing and reducing agents, macrogols and other hydroxy compounds, glycerol, glycols, some paraffins and ointment bases, preservatives such as chlorocresol or thiomersal, blood and blood products, and antibacterials such as amphotericin, cephalosporins, and vancomycin. Injections of benzylpenicillins and aminoglycosides should be administered separately. 

MACROGOL 400 BPC (107-21-1) Combustible liquid (flash point 23rF/lirC). Violent reaction with oxidizers and oxidizing acids, sulfuric acid. Forms explosive mixture with sodium perchlorate. Incompatible with strong acids, caustics, aliphatic amines,... 

A macrogol base will mostly be chosen based on published data showing better release or absorption, or both. The advantage of water solubility and thus avoidance of the melting time is somewhat overestimated because the dissolution of macrogol in the rectal fluid takes time as well. Once the macrogol has been dissolved the active substance release is faster than from a fatty base because in the latter transport of the active substance from the fatty to the aqueous phase still has to take place. Moreover the active substance can dissolve in the rectal fluid simultaneously with the base. The base has considerable disadvantages however chemical incompatibilities and irritation. 

A macrogol base is often discouraged because it would be irritating to the mucosa. Others report a good acceptance of the base. Irritation is assumed to be caused by the attraction of water from the mucosa. The available amount of water in the vagina varies individually. A slow or incomplete release of the active substance may result in case little liquid is available. Moreover macrogol is incompatible with many active substances, see Sect. 11.4.5. 

The selection of the surfactant is mainly based on the compatibility with the active substance. Sodium lauryl sulfate is an anionic surfactant and therefore incompatible with cationic active substances. Cetomacrogol emulsifying wax BP is incompatible with high concentrations of phenolic substances due to an interaction of the phenolic group with the polyethylene glycol chains in the macrogol cetostearyl ether. It is compatible with acids, high concentrations of electrolytes and cations. 

Polysorbate (Tween 20 and 80) and Cremophor RH40 (macrogol glycerol hydroxyl stearate) or Cremophor EL (polyoxylated 35 castor oil) can cause serious hypersensitivity reactions when administered parenterally [15]. They may cause incompatibilities by leaching plasticisers (such as phthalates) from polyvinyl chloride infusion devices. 

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