title: A novel aqueous parenteral formulation of docetaxel using prodrugs.
abstract: The aim of this study is to develop an aqueous parenteral solution of docetaxel using prodrugs. Docetaxel (DTX) is a highly lipophilic drug and practically insoluble in water. To overcome insolubility of docetaxel, three kinds of docetaxel prodrugs were synthesized using succinyl linker such as DTX-G, DTX-L or DTX-S and physicochemically characterized. The solubility of docetaxel prodrugs was determined by changing the concentration and type of surfactants, cosolvents or cyclodextrins. It was observed that the novel mixture of 15% PEG 400, 2.5% Tween 80 and 20% hydroxypropyl-β-cyclodextrin significantly increased the solubility of DTX-G up to 5.7 mg/mL. After subjected to the study of the hemolytic and cytotoxic activities, it was shown that the novel mixture did not show the hemolysis compared to Taxotere. It was suggested this novel mixture might have the potential to develop an aqueous parenteral formulation.
authors.affiliation: College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, South Korea.
authors.forename: Min-Ho
authors.initials: MH
authors.lastname: Park
authors.affiliation: College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, South Korea.
authors.forename: Chang-Gu
authors.initials: CG
authors.lastname: Keum
authors.affiliation: SamyangGenex, 63-2 Hwaam-dong, Yuseong-gu, Daejeon 305-717, South Korea.
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Song
authors.affiliation: GeneChem Inc., 59-5 Jang-dong, Yuseong-gu, Daejeon 305-343, South Korea.
authors.forename: Daehee
authors.initials: D
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, South Korea. Electronic address: chocw@cnu.ac.kr.
authors.forename: Cheong-Weon
authors.initials: CW
authors.lastname: Cho
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003505:Cyclodextrins / Q000737:chemistry; D000077143:Docetaxel; D005079:Excipients / Q000737:chemistry*; D006461:Hemolysis / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D011092:Polyethylene Glycols / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry; D011355:Prodrugs; D051381:Rats; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D043823:Taxoids / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D003505:Cyclodextrins; D005079:Excipients; D011136:Polysorbates; D011355:Prodrugs; D012997:Solvents; D043823:Taxoids; D000077143:Docetaxel; D011092:Polyethylene Glycols
keywords: Docetaxel; Hemolysis; Parenteral; Prodrug; Solubility