title: Docetaxel epimerization in silicone films: a case of drug excipient incompatibility.
abstract: Docetaxel (DTX) is an anti-cancer compound derived from 10-deacetyl baccatin III which is indicated for treatment of breast, lung, prostate, gastro-esophageal, and head and neck cancers. Epimerization of DTX at the C-7 hydroxyl position has intrigued chemists and has been implicated in loss of potency, as well as in the development of resistance in tumour cells. For localized controlled delivery of this agent, silicone films were prepared from a commercially available silicone kit. High levels of epimeric degradants were unexpectedly found in the in vitro release media. Herein, we discuss this anomalous DTX degradation to epimeric impurities, and discuss the possible reasons for degradation. Systematic stability studies were performed on the release media and the silicone kit components. It was found that release media and tin-based catalyst present in the silicone kit could be responsible for the epimeric conversion. This unusual case of chemical incompatibility can affect product performance and can even lead to development of resistance in tumour cells towards DTX.
authors.affiliation: Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, 5000, Australia.
authors.forename: Shaikh
authors.initials: S
authors.lastname: Mohsin
authors.forename: Ian Harvey
authors.initials: IH
authors.lastname: Arellano
authors.forename: Namita Roy
authors.initials: NR
authors.lastname: Choudhury
authors.forename: Sanjay
authors.initials: S
authors.lastname: Garg
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations; D000077143:Docetaxel; D004344:Drug Incompatibility; D065546:Drug Liberation; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D012828:Silicones / Q000737:chemistry*; D043823:Taxoids / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D005079:Excipients; D012828:Silicones; D043823:Taxoids; D000077143:Docetaxel
keywords: chemical incompatibility; degradation; docetaxel; epimerization; silicone