| Abstract: | Injection of phenytoin is often diluted with infusion fluids before administration, which may lead to precipitation of the drug due to changes in pH and/or vehicle. It is not possible to add cyclodextrins to the original injections to prevent precipitation of the drug, because the quantities required would be impractical (>100% w/v). However, from a knowledge of the solubility of phenytoin in cyclodextrin solutions, it is possible to add sufficient amounts of a soluble cyclodextrin to infusion fluids to maintain the solubility of phenytoin after the original injection is diluted to clinical concentrations in the fluid. From solubility measurements, theoretical amounts of hydroxypropyl β-cyclodextrin (HPCD), sufficient to prevent precipitation of phenytoin, were added to 0·9% w/v sodium chloride solution, adjusted to pH 7·0. Phenytoin injection was diluted to clinical concentrations in the cyclodextrin/NaCl solutions. The mixtures, together with analogous mixtures containing phenytoin, but no HPCD, were stored at 25 °C for 3 days. In the presence of the cyclodextrin no precipitates of phenytoin were observed, but in its absence an immediate massive precipitation of phenytoin occurred. This is a flexible method for using soluble cyclodextrins to prevent precipitates of drugs in infusion fluids, provided the cyclodextrin used is not toxic. |
