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Physical and chemical stability of paclitaxel infusions in different container types

School of Pharmacy and Chemistry, Kingston University, Kingston upon Thames, Surrey, UK

Graham J Sewell, PhD MRPharmS

School of Pharmacy and Chemistry, Kingston University, Penrhyn Road, Kingston upon Thames, Surrey KT1 2EE, UK g.j.sewell{at}kingston.ac.uk; Plymouth Hospitals NHS Trust, Plymouth, UK

Objectives. To determine the physicochemical stability of generic (Teva Pharmaceuticals) paclitaxel infusions (0.3 and 1.2 mg/mL) in 0.9% sodium chloride or 5% glucose in polyolefin (Viaflo®), low-density polyethylene (Ecoflac®), and glass containers at 2-8 and 25°C.

Methods. Paclitaxel infusions of various concentration/diluent/container combinations were prepared. Containers were light-protected and incubated at test temperatures with further analysis at predetermined intervals of 1-3 days for up to 30 days. Infusions were monitored for pH, weight loss, precipitation, colour change, and subvisual particulates as indicators of physical stability, and assayed for drug concentration to determine chemical stability.

Results. Precipitation was the limiting factor. Infusions of paclitaxel (0.3 mg/mL) in 0.9% sodium chloride remained stable for 13, 16 and 13 days at 2-8°C in polyolefin, low-density polyethylene and glass containers, respectively; in 5% glucose for 13, 18, and 20 days, respectively. At 25°C, paclitaxel infusions (0.3 mg/mL) remained stable for 3 days in all diluent/container combinations with the exception of 5% glucose in glass, where stability reached 7 days. Paclitaxel infusions (1.2 mg/mL) in 0.9% sodium chloride remained stable for 9, 12, and 8 days at 2-8°C in polyolefin, low-density polyethylene and glass containers, respectively; in 5% glucose for 10, 12, and 10 days, respectively. At 25°C, paclitaxel 1.2 mg/mL remained stable for 3 days in all diluent/container combinations with the exception of glass, where stability reached 5 days in 0.9% sodium chloride diluent, and 7 days in 5% glucose.

Conclusion. Paclitaxel stability was influenced by storage temperature, with longer shelf-life at 2-8°C, and also by drug concentration, where 0.3 mg/mL infusions were more stable than 1.2 mg/mL for all diluent/container combinations. Physical stability (precipitation) was the limiting parameter in each case.

Key Words: compatibility • generic • infusion • paclitaxel • stability

References

• Wani M, Taylore HL, Wall ME, Coggon P, McPhail AT. The isolation and structure of Taxol, a novel antileukemic and antitumor agent from Taxus brevifolia . J Am Chem Soc 1971; 93: 2325-2337 .[CrossRef][Medline] [Order article via Infotrieve]
• Rowinsky EK, Cazenave LA, Donehower RC. Taxol-A novel investigational antimicrotubule agent . J Natl Cancer Inst 1990; 82: 1247-1259 .[Abstract/Free Full Text]
• Donehower RC, Rowinsky EK, Grochow LB, Longenecke SM, Ettinger DS. Phase I trial of Taxol in patients with advanced cancer . Cancer Treat Rep 1987; 71: 1171-1177 .[Medline] [Order article via Infotrieve]
• Huizing MT, Misser VH, Pieters RC, ten BokkelHuinink WW, Veenhof CH, Vermorken JB, Pinedo HM, Beijnen JH. Taxanes: a new class of antitumor agents . Cancer Invest 1995; 13: 381-404 .[Medline] [Order article via Infotrieve]
• Lee J, Lee SC, Acharya G, Chang C, Park K. Hydrotropic solubilization of paclitaxel: analysis of chemical structures for hydrotropic property . Pharm Res 2003; 20: 1022-1030 .[CrossRef][Medline] [Order article via Infotrieve]
• Mathew AE, Mejillano MR, Nath JP, Himes RH, Stella VJ. Synthesis and evaluation of some water-insoluble prodrugs and derivatives of Taxol with antitumor activity . J Med Chem 1992; 35: 145-145 .[CrossRef][Medline] [Order article via Infotrieve]
• Panchagnula R. Pharmaceutical aspects of paclitaxel . Int J Pharm 1998; 172: 1-15 .[CrossRef]
• Rowinsky E, Donehower RC. Taxol: twenty years later, the story unfolds . J Natl Cancer Inst 1991; 83: 1778-1781 .[Free Full Text]
• Weiss RB, Donehower RC, Wiernik PH, Hnuma T, Gralla RJ, Trump DL, Baker JR, Van Echo DA, Von Hoff DD, Leyland-Jones B. Hypersensitivity reactions from Taxol . J Clin Oncol 1990; 8: 1263-1268 .[Abstract]
• Dorr RT. Pharmacology and toxicology of Cremophor EL diluent . Ann Pharmacother 1994; 28: 511-514 .
• Mazzo DJ, Nguyen-Huu J-J, Pagniez S, Denis P. Compatibility of docetaxel and paclitaxel in intravenous solutions with polyvinyl chloride infusion materials . Am J Health-Syst Pharm 1997; 54: 566-569 .[Free Full Text]
• Allwood M, Martin H. The extraction of diethylhexylphthalate (DEHP) from polyvinyl chloride components of intravenous infusion containers and administration sets by paclitaxel injection . Int J Pharm 1996; 127: 65-71 .[CrossRef]
• Summerhayes M, Daniels S eds. Practical chemotherapy. Radcliffe Medical Press , 2003: 275-275.
• Waugh W, Trissel LA, Stella VJ. Stability, compatibility and plasticizer extraction of Taxol (NSC 125973) injection diluted in infusion solutions and stored in various containers . Am J Hosp Pharm 1991; 48: 1520-1524 .[Abstract]
• Krammer I, Heuser A. Paclitaxel pharmaceutical and pharmacological issues . Eur Hosp Pharm 1995; 1: 37-41 .
• Straubinger RM. Biopharmaceutics of paclitaxel (Taxol): formulation, activity and pharmacokinetics. In Suffness M ed. Taxol: science and applications. CRC Press , 1995: 237-254.
• Adams JD, Flora KP, Goldspiel BR. Taxol: a history of pharmaceutical development and current pharmaceutical concerns . J Natl Cancer Inst 1993; 15: 141-147 .
• Plumridge RJ, Sewell GJ. Dose-banding of cytotoxic drugs: a new concept in cancer chemotherapy . Am J Health-Syst Pharm 2001; 58: 1760-1764 .[Free Full Text]
• Sautou-Miranda V, Brigas F, Vanheerswynghels S, Chopineau J. Compatibility of paclitaxel in 5% glucose solution with ECOFLAC®; low-density polyethylene containersstability under different storage conditions . Int J Pharm 1999; 178: 77-82 .[CrossRef][Medline] [Order article via Infotrieve]
• Xu Q, Trissel LA, Martinez JF. Stability of paclitaxel in 5% dextrose injection or 0.9% sodium chloride injection at 4, 22, or 32 DGC . Am J Hosp Pharm 1994; 51: 3058-3060 .[Medline] [Order article via Infotrieve]

Journal of Oncology Pharmacy Practice, Vol. 12, No. 4, 211-222 (2006)
DOI: 10.1177/1078155206073589


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Donyai, P. Articles by Sewell, G. J Search for Related Content PubMed PubMed Citation Articles by Donyai, P. Articles by Sewell, G. J Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB GLUCOSE SODIUM CHLORIDE TAXOL Social Bookmarking                         What's this?