title: 2-Hydroxypropyl-beta-cyclodextrin extracts 2-phenylphenol from silicone tubing.
abstract: 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-beta-cyclodextrin (HPbetaCD) 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 HPbetaCD solutions after incubation with platinum cured silicone tubing. HPbetaCD 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 HPbetaCD solutions. 2-PP was extracted from silicone tubing during routine manufacture of a blank dosage form formulated with only HPbetaCD, resulting in detectable levels of 2-PP in the final product. In a freeze-dried dosage form containing HPbetaCD and an active pharmaceutical ingredient (exhibiting a stability constant for HPbetaCD/drug of 1045 L/mol), on the other hand, 2-PP was undetectable.
authors.affiliation: Slotervaart Hospital/The Netherlands Cancer Institute, Department of Pharmacy & Pharmacology, 1066 EC Amsterdam. apmbk@slz.nl
authors.forename: Monique W J
authors.initials: MW
authors.lastname: den Brok
authors.forename: Sabien C
authors.initials: SC
authors.lastname: van der Schoot
authors.forename: Bastiaan
authors.initials: B
authors.lastname: Nuijen
authors.forename: Michel J X
authors.initials: MJ
authors.lastname: Hillebrand
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D001713:Biphenyl Compounds / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003505:Cyclodextrins / Q000737:chemistry*; D000431:Ethanol / Q000737:chemistry; D013058:Mass Spectrometry; D044367:Phase Transition; D011310:Preservatives, Pharmaceutical / Q000737:chemistry*; D012828:Silicones / Q000737:chemistry*; D013678:Technology, Pharmaceutical; D047392:beta-Cyclodextrins
chemical_list: D001713:Biphenyl Compounds; D003505:Cyclodextrins; D011310:Preservatives, Pharmaceutical; D012828:Silicones; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000431:Ethanol; C004369:2-phenylphenol