title: Influence of long-term stability conditions on microbicidal nucleoside prodrug (WHI-07)-loaded gel-microemulsion.
abstract: The objective of this study was to evaluate the long-term stability of the antiretroviral spermicide WHI-07 (5-bromo-6-methoxy-5,6-dihydro-3'-azidothymidine-5'-(p-bromophenyl)-methoxyalaninyl phosphate) in a polymer-based microemulsion. The recovery and stability of WHI-07 in gel-microemulsion was examined by a validated high-performance liquid chromatography (HPLC) method. The stability was examined over a period of 24 weeks at 3 controlled temperatures (4 degrees C, 25 degrees C, and 40 degrees C). The recovery of the prodrug from 0.5% to 2.0% WHI-07-loaded gel-microemulsion was 99.8%. HPLC analysis revealed that a 2% WHI-07-loaded gel-microemulsion stored at room temperature and cold temperatures for 24 weeks retained >90% of the prodrug, whereas those stored at 40 degrees C maintained 90% of initial WHI-07 for at least 10 weeks. The observed stability of WHI-07 in gel-microemulsion is of great importance for its widespread utility in various climatological conditions.
authors.affiliation: Drug Discovery Program, Parker Hughes Institute, St Paul, MN 55113, USA. odcruz@ih.org
authors.forename: Osmond J
authors.initials: OJ
authors.lastname: D'Cruz
authors.forename: Fatih M
authors.initials: FM
authors.lastname: Uckun
mesh_terms: D054306:Dideoxynucleotides; D004355:Drug Stability; D004655:Emulsions; D009705:Nucleosides / Q000737:chemistry; D011355:Prodrugs / Q000737:chemistry*; D013696:Temperature; D013938:Thymidine Monophosphate / Q000031:analogs & derivatives* / Q000737:chemistry; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: C114570:5-bromo-6-methoxy-5, 6-dihydro-3'-azidothymidine-5'-(p-bromophenyl) methoxyalaninyl phosphate; D054306:Dideoxynucleotides; D004655:Emulsions; D009705:Nucleosides; D011355:Prodrugs; D013938:Thymidine Monophosphate; D015215:Zidovudine