title: Vaginal film drug delivery of the pyrimidinedione IQP-0528 for the prevention of HIV infection.
abstract: OBJECTIVE
  Polymeric quick-dissolving films were developed as a solid dosage topical microbicide formulation for the vaginal delivery of the highly potent and non-toxic, dual-acting HIV nonnucleoside reverse transcriptase inhibitor (NNRTI) pyrimidinedione, IQP-0528.
  
  
  METHODS
  Formulated from approved excipients, a polyvinyl alcohol (PVA) based film was manufactured via solvent casting methods. The film formulations were evaluated based upon quantitative physicochemical evaluations defined by a Target Product Profile (TPP)                                               RESULTS:                          Films dosed with 0.1% (w/w) of IQP-0528 disintegrated within 10 min with over 50% of drug released and near 100% total drug released after 30 min. The IQP-0528 films were found to be non-toxic in in vitro CEM-SS and PBMC cell-based assays and biologically active with sub-nanomolar efficacy against HIV-1 infection. In a 12 month stability protocol, the IQP-0528 films demonstrated no significant degradation at International Conference on Harmonization (ICH) recommended standard (25°C/65% relative humidity (R.H.)) and accelerated (40°C/75% R.H.) environmental conditions.
  
  
  CONCLUSIONS
  Based on the above evaluations, a vaginal film formulation has been identified as a potential solid dosage form for the vaginal delivery of the topical microbicide candidate IQP-0528.
authors.affiliation: ImQuest BioSciences Inc., 7340 Executive Way, Suite R, Frederick, Maryland 21704, USA. aham@imquestbio.com
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Ham
authors.forename: Lisa Cencia
authors.initials: LC
authors.lastname: Rohan
authors.forename: Ashlee
authors.initials: A
authors.lastname: Boczar
authors.forename: Lu
authors.initials: L
authors.lastname: Yang
authors.forename: Karen
authors.initials: K
authors.lastname: W Buckheit
authors.forename: Robert W
authors.initials: RW
authors.lastname: Buckheit
mesh_terms: D000282:Administration, Intravaginal; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology; D011744:Pyrimidinones / Q000008:administration & dosage* / Q000494:pharmacology; D014621:Vagina / Q000378:metabolism*
chemical_list: D019380:Anti-HIV Agents; C573126:IQP-0528; D011744:Pyrimidinones