Submicron matrices embedded in a polymeric caplet for extended intravaginal delivery of Zidovudine

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dc.contributor.author Mashingaidze, Felix
dc.contributor.author Choonara, Yahya E.
dc.contributor.author Kumar, Pradeep
dc.contributor.author Du Toit, Lisa C.
dc.contributor.author Maharaj, Vinesh J.
dc.contributor.author Buchmann, Eckhart
dc.contributor.author Pillay, Viness
dc.date.accessioned 2017-09-04T06:26:43Z
dc.date.issued 2017-11
dc.description This study was derived from the Master’s dissertation of first author, Felix Mashingaidze, submitted 24 March 2014. en_ZA
dc.description.abstract In this study, an intravaginal delivery system able to deliver an anti-HIV-1 agent for the purpose of potentially reducing HIV-1 transmission acting over an extended duration was successfully formulated. This delivery system was a composite polymeric caplet comprising zidovudine-loaded polyethylene glycol enclatherated pectin-mucin submicron matrices embedded within a poly (D,L-lactide), magnesium stearate, Kollidon® SR, and Carbopol® 974P NF-based polymeric caplet matrix. A three-factor and three-level Box-Behnken statistical design was utilized to optimize the polymeric caplet. The optimized directly compressed composite polymeric caplet hardness was 22.1 ± 0.3 N and the matrix resilience was 62.4 ± 0.6%. The swelling- and diffusion-controlled fractional zidovudine (AZT) release from the optimized caplet was 0.74 ± 0.01 in simulated vaginal fluid (SVF), which increased to 0.81 ± 0.21 in phosphate-buffered saline (PBS) simulating seminal fluid, over 30 days. Caplet matrix swelling was directly related to the percentage Carbopol 974P NF composition. An intravaginal system for AZT delivery was tested in the pig model over 28 days. X-ray analysis depicted delivery system swelling with matrix contrast fading over time as vaginal fluid permeated the matrix core. Plasma, vaginal fluid swab eluates, and tissue AZT concentrations were measured by gradient ultra-performance liquid chromatography (UPLC)-tandem photodiode array detection. Vaginal tissue and vaginal fluid swab eluate AZT concentrations remained above effective levels over 28 days and were higher than plasma AZT concentrations, availing a system with reduced systemic toxicity and more effective inhibition of viral replication at the site of entry. en_ZA
dc.description.department Chemistry en_ZA
dc.description.embargo 2018-11-04
dc.description.librarian hj2017 en_ZA
dc.description.sponsorship The Council for Scientific and Industrial Research, South Africa (CSIR SA), the South African National Research Foundation (NRF) and the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. en_ZA
dc.description.uri https://link.springer.com/journal/12248 en_ZA
dc.identifier.citation Mashingaidze, F., Choonara, Y.E., Kumar, P. et al. Submicron Matrices Embedded in a Polymeric Caplet for Extended Intravaginal Delivery of Zidovudine. AAPS Journal (2017) 19: 17451759. https://doi.org/10.1208/s12248-017-0130-4. en_ZA
dc.identifier.issn 1550-7416 (online)
dc.identifier.other 10.1208/s12248-017-0130-4
dc.identifier.uri http://hdl.handle.net/2263/62169
dc.language.iso en en_ZA
dc.publisher Springer en_ZA
dc.rights © 2017 American Association of Pharmaceutical Scientists. The original publication is available at : https://link.springer.com/journal/12248. en_ZA
dc.subject Histopathology en_ZA
dc.subject Zidovudine (AZT) en_ZA
dc.subject X-ray imaging en_ZA
dc.subject Intravaginal drug delivery en_ZA
dc.subject Simulated vaginal fluid (SVF) en_ZA
dc.subject Ultra-performance liquid chromatography (UPLC) en_ZA
dc.title Submicron matrices embedded in a polymeric caplet for extended intravaginal delivery of Zidovudine en_ZA
dc.type Postprint Article en_ZA


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