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Compartmental transport model of microbicide delivery by an intravaginal ring.

Publication ,  Journal Article
Geonnotti, AR; Katz, DF
Published in: Journal of pharmaceutical sciences
August 2010

Topical antimicrobials, or microbicides, are being developed to prevent HIV transmission through local, mucosal delivery of antiviral compounds. While hydrogel vehicles deliver the majority of current microbicide products, intravaginal rings (IVRs) are an alternative microbicide modality in preclinical development. IVRs provide a long-term dosing alternative to hydrogel use, and might provide improved user adherence. IVR efficacy requires sustained delivery of antiviral compounds to the entire vaginal compartment. A two-dimensional, compartmental vaginal drug transport model was created to evaluate the delivery of drugs from an intravaginal ring. The model utilized MRI-derived ring geometry and location, experimentally defined ring fluxes and vaginal fluid velocities, and biophysically relevant transport theory. Model outputs indicated the presence of potentially inhibitory concentrations of antiviral compounds along the entire vaginal canal within 24 h following IVR insertion. Distributions of inhibitory concentrations of antiviral compounds were substantially influenced by vaginal fluid flow and production, while showing little change due to changes in diffusion coefficients or ring fluxes. Additionally, model results were predictive of in vivo concentrations obtained in clinical trials. Overall, this analysis initiates a mechanistic computational framework, heretofore missing, to understand and evaluate the potential of IVRs for effective delivery of antiviral compounds.

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Published In

Journal of pharmaceutical sciences

DOI

EISSN

1520-6017

ISSN

0022-3549

Publication Date

August 2010

Volume

99

Issue

8

Start / End Page

3514 / 3521

Related Subject Headings

  • Vagina
  • Software
  • Reverse Transcriptase Inhibitors
  • Pyrimidines
  • Pharmacology & Pharmacy
  • Mucous Membrane
  • Magnetic Resonance Imaging
  • Kinetics
  • Humans
  • HIV Reverse Transcriptase
 

Citation

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Geonnotti, A. R., & Katz, D. F. (2010). Compartmental transport model of microbicide delivery by an intravaginal ring. Journal of Pharmaceutical Sciences, 99(8), 3514–3521. https://doi.org/10.1002/jps.22120
Geonnotti, Anthony R., and David F. Katz. “Compartmental transport model of microbicide delivery by an intravaginal ring.Journal of Pharmaceutical Sciences 99, no. 8 (August 2010): 3514–21. https://doi.org/10.1002/jps.22120.
Geonnotti AR, Katz DF. Compartmental transport model of microbicide delivery by an intravaginal ring. Journal of pharmaceutical sciences. 2010 Aug;99(8):3514–21.
Geonnotti, Anthony R., and David F. Katz. “Compartmental transport model of microbicide delivery by an intravaginal ring.Journal of Pharmaceutical Sciences, vol. 99, no. 8, Aug. 2010, pp. 3514–21. Epmc, doi:10.1002/jps.22120.
Geonnotti AR, Katz DF. Compartmental transport model of microbicide delivery by an intravaginal ring. Journal of pharmaceutical sciences. 2010 Aug;99(8):3514–3521.
Journal cover image

Published In

Journal of pharmaceutical sciences

DOI

EISSN

1520-6017

ISSN

0022-3549

Publication Date

August 2010

Volume

99

Issue

8

Start / End Page

3514 / 3521

Related Subject Headings

  • Vagina
  • Software
  • Reverse Transcriptase Inhibitors
  • Pyrimidines
  • Pharmacology & Pharmacy
  • Mucous Membrane
  • Magnetic Resonance Imaging
  • Kinetics
  • Humans
  • HIV Reverse Transcriptase