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

dc.contributor.authorMashingaidze, Felix
dc.contributor.authorChoonara, Yahya E.
dc.contributor.authorKumar, Pradeep
dc.contributor.authorDu Toit, Lisa C.
dc.contributor.authorMaharaj, Vinesh J.
dc.contributor.authorBuchmann, Eckhart
dc.contributor.authorPillay, Viness
dc.date.accessioned2017-09-04T06:26:43Z
dc.date.issued2017-11
dc.descriptionThis study was derived from the Master’s dissertation of first author, Felix Mashingaidze, submitted 24 March 2014.en_ZA
dc.description.abstractIn 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.departmentChemistryen_ZA
dc.description.embargo2018-11-04
dc.description.librarianhj2017en_ZA
dc.description.sponsorshipThe 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.urihttps://link.springer.com/journal/12248en_ZA
dc.identifier.citationMashingaidze, 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.issn1550-7416 (online)
dc.identifier.other10.1208/s12248-017-0130-4
dc.identifier.urihttp://hdl.handle.net/2263/62169
dc.language.isoenen_ZA
dc.publisherSpringeren_ZA
dc.rights© 2017 American Association of Pharmaceutical Scientists. The original publication is available at : https://link.springer.com/journal/12248.en_ZA
dc.subjectHistopathologyen_ZA
dc.subjectZidovudine (AZT)en_ZA
dc.subjectX-ray imagingen_ZA
dc.subjectIntravaginal drug deliveryen_ZA
dc.subjectSimulated vaginal fluid (SVF)en_ZA
dc.subjectUltra-performance liquid chromatography (UPLC)en_ZA
dc.titleSubmicron matrices embedded in a polymeric caplet for extended intravaginal delivery of Zidovudineen_ZA
dc.typePostprint Articleen_ZA

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