Cyclodextrins are capable to solubilise lipophilic drugs via (partial) inclusion in their lipophilic cavity. This, however, also provides the potential for the extraction of small molecules from production materials. In the present study, the potency of the commercially available and used cyclodextrin, 2-hydroxypropyl-β-cyclodextrin (HPβCD) to extract the preservative 2-phenylphenol (2-PP) from platinum cured silicone tubing was tested. The presence of 2-PP was structurally confirmed with HPLC–UV and LC/MS/MS in HPβCD solutions after incubation with platinum cured silicone tubing. HPβCD concentration and prior tubing sterilisation were found not to influence the levels of 2-PP extracted. Interestingly, extraction to ethanol was 15-fold higher than observed for HPβCD solutions.
2-PP was extracted from silicone tubing during routine manufacture of a blank dosage form formulated with only HPβCD, resulting in detectable levels of 2-PP in the final product. In a freeze-dried dosage form containing HPβCD and an active pharmaceutical ingredient (exhibiting a stability constant for HPβCD/drug of 1045 L/mol), on the other hand, 2-PP was undetectable.