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Investigational New Drugs

, Volume 19, Issue 2, pp 143–153 | Cite as

Progress in the Development of Alternative Pharmaceutical Formulations of Taxanes

  • Bastiaan Nuijen
  • Marjan Bouma
  • Jan H.M. Schellens
  • Jos H. Beijnen
Article

Abstract

The currently available taxanes paclitaxel(Taxol®) and docetaxel(Taxotere®) are clinically effectiveagainst advanced breast, ovarian andnon-small cell lung cancer. Due to theirlow aqueous solubility, both taxanes poseddifficulties to the pharmaceuticalscientists with respect to the developmentof an intravenous dosage form. At present,paclitaxel is formulated in a mixture of50:50% (v/v) Cremophor EL and dehydratedethanol. However, this formulation vehicleis associated with a number ofpharmacological, pharmacokinetic andpharmaceutical concerns amongst whichserious hypersensitivity reactions. Thisreview deals with the attempts made intothe development of alternative dosage formsof paclitaxel devoid of the CremophorEL/ethanol excipients and potential futuretaxane formulations.

taxanes paclitaxel docetaxel alternative formulation co-solvents surfactants emulsions micro-encapsulation systems liposomes cyclodextrines prodrugs 

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References

  1. 1.
    Huizing MT, Sewberath Misser VH, Pieters RC, ten Bokkel Huinink WW, Veenhof CHN, Vermorken JB, Beijnen JH: Taxanes: a new class of antitumor agents. Cancer Inv 13: 381–404, 1995Google Scholar
  2. 2.
    Straubinger RM: Biopharmaceutics of paclitaxel (Taxol): formulation, activity, and pharmacokinetics. In: Suffness M (ed) Taxolr: Science and Applications. CRC press, 1996, pp 237–258Google Scholar
  3. 3.
    Adams JD, Flora KP, Goldspiel BR, Wilson JW, Arbuck SG, Finley R: Taxol: a history of pharmaceutical development and current pharmaceutical concerns. J Natl Cancer Inst 15: 141–147, 1993Google Scholar
  4. 4.
    Meerum Terwogt JM, Nuijen B, Ten Bokkel Huinink WW, Beijnen JH: Alternative formulations of paclitaxel. Canc Treat Rev 23: 87–95, 1997Google Scholar
  5. 5.
    Nannan Panday VR, Huizing MT, ten Bokkel Huinink WW, Vermorken JB, Beijnen JH: Hypersensitivity reactions to the taxanes paclitaxel and docetaxel. Clin Drug Invest 14: 418–427, 1997Google Scholar
  6. 6.
    Lorenz W, Reimann HJ, Schmal A, Dormann P, Schwarz B, Neugebauer E, Doenicke A: Histamine release in dogs by Cremophor ELr and its derivatives: oxethylated oleic acid is the most effective constituent. Agents Actions 7: 63–67, 1977PubMedGoogle Scholar
  7. 7.
    Wilson DB, Beck TM, Gundlach CA: Paclitaxel formulation as a cause of ethanol intoxication. Ann Pharmacother 31: 873–875, 1997PubMedGoogle Scholar
  8. 8.
    Sparreboom A, van Tellingen O, Nooijen WJ, Beijnen JHM: Nonlinear pharmacokinetics of paclitaxel in mice results from the pharmaceutical vehicle Cremophor EL. Canc Res 56: 2112–2115, 1996Google Scholar
  9. 9.
    van Tellingen O, Huizing MT, Panday VR, Schellens JH, Nooijen WJ, Beijnen JH: Cremophor EL causes (pseudo-) non-linear pharmacokinetics of paclitaxel in patients. Br J Cancer 81: 330–335, 1999PubMedGoogle Scholar
  10. 10.
    Liebmann J, Cook J, Lipschultz C: The influence of Cremophor EL on the cell cycle effects of paclitaxel (Taxol) in human tumor cell lines. Cancer Chemother Pharmacol 33: 331–339, 1994PubMedGoogle Scholar
  11. 11.
    Trissel LA: Pharmaceutical properties of paclitaxel and their effects on preparation and administration. Pharmacotherapy 17: 133S–139S, 1997PubMedGoogle Scholar
  12. 12.
    Jonkman-de Vries JD, Flora KP, Bult A, Beijnen JH: Pharmaceutical development of (investigational) anticancer agents for parenteral use – a review. Drug Develop Indust Pharm 22: 475–494, 1996Google Scholar
  13. 13.
    Sweetana S, Akers MJ: Solubility principles and practices for parenteral drug dosage form development. PDA J Pharm Sci Technol 50: 330–342, 1996PubMedGoogle Scholar
  14. 14.
    Product information Taxol (Bristol-Myers Squibb, Princeton, US)Google Scholar
  15. 15.
    Ramaswamy M, Zhang X, Burt HM, Wasan KM: Human plasma distribution of free paclitaxel and paclitaxel associated with diblock copolymers. J Pharm Sci 86: 460–464, 1997PubMedGoogle Scholar
  16. 16.
    Zhang X, Burt HM, Von Hoff D, Dexter D, Mangold G, Degen D, Oktaba AM, Hunter WL: An investigation of the antitumour activity and biodistribution of polymeric micellar paclitaxel. Cancer Chemother Pharmacol 40: 81–86, 1997PubMedGoogle Scholar
  17. 17.
    Zhang X, Burt HM, Mangold G, Dexter D, Von Hoff D, Mayer L, Hunter WL: Anti-tumor efficacy and biodistribution of intravenous polymeric micellar paclitaxel. Anticancer Drugs 8: 696–701, 1997PubMedGoogle Scholar
  18. 18.
    Product information Taxotere (Rhône-Poulenc Rorer)Google Scholar
  19. 19.
    Tarr BD, Sambandan TG, Yalkowsky SH: A new parenteral emulsion for the administration of Taxol. Pharm Res 4: 162–165, 1987PubMedGoogle Scholar
  20. 20.
    Simamora P, Dannenfelser RM, Tabibi SE, Yalkowski SH: Emulsion formulations for intavenous administration of paclitaxel. PDA J Pharm Sci Technol 52: 170–172, 1998PubMedGoogle Scholar
  21. 21.
    Lundberg BB: A submicron lipid emulsion coated with amphipathic polyethylene glycol for parenteral administration of paclitaxel (Taxol). J Pharm Pharmacol 49: 16–21, 1997PubMedGoogle Scholar
  22. 22.
    Kan P, Chen ZB, Lee CJ, Chu IM: Development of nonionic surfactant/phospholipid o/w emulsion as a paclitaxel delivery system. J Controlled Release 58: 271–278, 1999Google Scholar
  23. 23.
    Bartoli MH, Boitard M, Fessi H, Beriel H, Devissaguet JP, Picot F, Puisieux F: In vitro and in vivo antitumoral activity of free, and encapsulated taxol. J Microencapsulation 7: 191–197, 1990PubMedGoogle Scholar
  24. 24.
    Sharma D, Chelvi TP, Chakravorty K, De TK, Maitra A, Ralhan R: Novel Taxol formulation: polyvinylpyrrolidone nanoparticle-encapsulated Taxol for drug delivery in cancer therapy. Oncol Res 8: 281–286, 1996PubMedGoogle Scholar
  25. 25.
    Dordunoo SK, Jackson JK, Arsenault LA: Taxol encapsulation in poly(—-caprolactone) microspheres. Cancer Chemother Pharmacol 36: 279–282, 1995PubMedGoogle Scholar
  26. 26.
    Burt HM, Jackson JK, Bains SK, Liggins RT, Oktaba AM, Arsenault AL, Hunter WL. Controlled delivery of taxol from microspheres composed of a blend of ethylene-vinyl acetate copolymer and poly (d,l-lactic acid). Cancer Lett 88: 73–79, 1995PubMedGoogle Scholar
  27. 27.
    Harper E, Dang W, Lapidus RG, Garver RI: Enhanced efficacy of a novel controlled release paclitaxel formulation (PACLIMER Delivery System) for local-regional therapy of lung cancer tumor nodules in mice. Clin Canc Res 5: 4242–4248, 1999Google Scholar
  28. 28.
    Alkan-Onyuksel H, Ramakrishnan S, Chai HB, Pezzuto JM: A mixed micellar formulation suitable for the parenteral administration of Taxol. Pharm Res 11: 206–212Google Scholar
  29. 29.
    Straubinger RM, Sharma A, Murray M, Mayhew E: Novel Taxol formulations: Taxol containing liposomes. J Natl Cancer Inst Mon 15: 69–78, 1993Google Scholar
  30. 30.
    Sharma A, Straubinger RM: Novel Taxol formulations: preparation and characterization of Taxol-containing liposomes. Pharm Res 11: 889–896, 1994PubMedGoogle Scholar
  31. 31.
    Sharma A, Mayhew E, Bolcsak L, Cavanaugh C, Harmon P, Janoff A, Bernacki RJ: Activity of paclitaxel liposome formulations against human ovarian tumor xenografts. Int J Canc 71: 103–107, 1997Google Scholar
  32. 32.
    Bekers O, Uijtendaal EV, Beijnen JH, Bult A, Underberg WJM: Cyclodextrins in the pharmaceutical field. Drug Dev Ind Pharm 17: 1503–1549, 1991Google Scholar
  33. 33.
    Loftsson T, Brewster ME: Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization. Pharm Sci 85: 1017–1025, 1996Google Scholar
  34. 34.
    Sharma US, Balasubramanian SV, Straubinger RM: Pharmaceutical and physical properties of paclitaxel (Taxol) complexes with cyclodextrines. J Pharm Sci 84: 1223–1230, 1995PubMedGoogle Scholar
  35. 35.
    Mellado W, Magri NF, Kingston DGI, Garcia-Arenas R, Orr GA, Horwitz SB: Preparation and biological activity of taxol acetates. Biochem Biophys Res Com 124: 329–336, 1984PubMedGoogle Scholar
  36. 36.
    Vyas DM, Wong H, Crosswell AR, Casazza AM, Knipe JO, Mamber SW, Doyle TW: Synthesis and antitumor evaluation of water soluble taxol phosphates. Bioorganic Med Chem Lett 3: 1357–1360, 1993Google Scholar
  37. 37.
    Vyas DM: Paclitaxel (Taxolr) formulation and prodrugs. In: Farina V (ed) The Chemistry and Pharmacology of Taxol and its Derivatives, 103–130, 1995Google Scholar
  38. 38.
    Ueda Y, Mikkilineni AB, Knipe JO, Rose WC, Casazza AM, Vyas DM: Novel water soluble phosphate prodrugs of Taxolr possessing in vivo antitumor activity. Bioorganic Med Chem Lett 3: 1761–1766, 1993Google Scholar
  39. 39.
    Ueda Y, Wong H, Matiskella JD, Mikkelineni AB, Farina V, Fairchild C, Rose WC, Mamber SW, Long BH, Kerns EH, Casazza AM, Vyas DM: Synthesis and antitumor evaluation of 20-oxycarbonylpaclitaxels (paclitaxel-20-carbonates). Bioorganic Med Chem Lett 4: 1861–1864, 1994Google Scholar
  40. 40.
    Mathew AE, Mejillano MR, Nath JP, Himes RH, Stella VJ: Synthesis and evaluation of some water-soluble prodrugs and derivatives of Taxol with antitumor activity. J Med Chem 35: 145–151, 1992PubMedGoogle Scholar
  41. 41.
    Paradis R, Pagé M: New active paclitaxel amino acids derivatives with improved water solubility. Anticancer Res 18: 2711–2716, 1998PubMedGoogle Scholar
  42. 42.
    Nicolaou KC, Riemer C, Kerr MA, Rideout D, Wrasidlo W: Design, synthesis and biological activity of protaxols. Nature 364: 464–466, 1993PubMedGoogle Scholar
  43. 43.
    Greenwald RB, Pendri A, Bolikal D, Gilbert CW: Highly water-soluble taxol derivatives: 20-polyethyleneglycol esters as potential prodrugs. Biorganic Med Chem Lett 4: 2465–2470, 1994Google Scholar
  44. 44.
    Greenwald RB, Gilbert CW, Pendri A, Conover CD, Xia J, Martinez A: Drug delivery systems: water soluble Taxol 20-poly(ethylene glycol) ester prodrugs-design and in vivo effectiveness. J Med Chem 39: 424–431, 1996PubMedGoogle Scholar
  45. 45.
    Li C, Yu D, Inoue T, Yang DJ, Milas L, Hunter NR, Kim EE, Wallace S: Synthesis and evaluation of water-soluble polyethylene glycol-paclitaxel conjugate as a paclitaxel prodrug. Anticancer Drugs 7: 642–648, 1996PubMedGoogle Scholar
  46. 46.
    Pendri A, Conover CD, Greenwald RB: Antitumor activity of paclitaxel-20-glycinate conjugated to poly(ethylene glycol): a water soluble prodrug. Anticancer Drug Des 13: 387–395, 1998PubMedGoogle Scholar
  47. 47.
    Dosio F, Brusa P, Crosasso, P, Arpicco S, Cattel L: Preparation and characterization and properties in vitro and in vivo of a paclitaxel-albumin conjugate. J Control Rel 47: 293–304, 1997Google Scholar
  48. 48.
    Presenti E, Franzetti C, Biasoli G: Synthesis and biological activity of water soluble polymer-bound taxol derivatives. Proc Am Ass Cancer Res 36: 307, 1995Google Scholar
  49. 49.
    Ojima I, Park YH, Sun CM, Fenoglio I, Appendino G, Pera P, Bernacki RJ: Structure-activity relationships of new taxoids derived from 14—-hydroxy-10-deacetylbaccatin III. J Med Chem 37: 1408–1410, 1994PubMedGoogle Scholar
  50. 50.
    Ali SM, Hoemann MZ, Aubé J, Mitscher LA, Georg GI: Novel cytotoxic 30-(tert-butyl) 30-diphenyl analogs of paclitaxel and docetaxel. J Med Chem 38: 3821–3828, 1995PubMedGoogle Scholar
  51. 51.
    Alder JD, Jarvis KP, Marsh KC, Klein LL, Clement JJ: Preclinical in vivo efficacy of two 9-dihydrotaxane analogues against human and murine tumors. Br J Cancer 73: 560–564, 1996PubMedGoogle Scholar
  52. 52.
    Merisko-Liversidge E, Sarpotdar P, Bruno J, Hajj S, Wei L, Peltier N, Rake J, Shaw JM, Pugh S, Polin L, Jones J, Corbett T, Cooper E, Liversidge GG: Formulation and antitumor activity evaluation of nanocrystalline suspensions of poorly soluble drugs. Pharm Res 13: 272–278, 1996PubMedGoogle Scholar
  53. 53.
    Winternitz CI, Jackson JK, Oktaba AM, Burt HM: Development of a polymeric surgical paste formulation for taxol. Pharm Res 13: 368–375, 1996PubMedGoogle Scholar
  54. 54.
    Smith J, Stock E, Orenberg EK, Yu NY, Kanekal S, Brown DM: Intratumoral chemotherapy with sustained-release drug delivery system inhibits growth of human pancreatic cancer xenografts. Anticancer Drugs 6: 717–726, 1995PubMedGoogle Scholar
  55. 55.
    Meerum Terwogt JM, Beijnen JH, ten Bokkel Huinink WW, Rosing H, Schellens JHM: Co-administration of cyclosporin enables oral therapy with paclitaxel. Lancet 352: 285, 1998Google Scholar

Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Bastiaan Nuijen
    • 1
  • Marjan Bouma
    • 1
  • Jan H.M. Schellens
    • 1
  • Jos H. Beijnen
    • 1
  1. 1.Department of Pharmacy and PharmacologySlotervaart Hospital/The Netherlands Cancer InstituteAmsterdamThe Netherlands

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