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Article

Performance and Stability of Tenofovir Alafenamide Formulations within Subcutaneous Biodegradable Implants for HIV Pre-Exposure Prophylaxis (PrEP)

1
Engineered Systems, RTI International, 3040 E Cornwallis Road, Research Triangle Park, Durham, NC 27709, USA
2
Women’s Global Health Imperative, RTI International, 2150 Shattuck avenue, Berkeley, CA 94704, USA
*
Author to whom correspondence should be addressed.
Pharmaceutics 2020, 12(11), 1057; https://doi.org/10.3390/pharmaceutics12111057
Received: 8 October 2020 / Revised: 29 October 2020 / Accepted: 30 October 2020 / Published: 5 November 2020
(This article belongs to the Special Issue Controlled Delivery Formulations)
A critical need exists to develop diverse biomedical strategies for the widespread use of HIV Pre-Exposure Prophylaxis (HIV PrEP). This manuscript describes a subcutaneous reservoir-style implant for long-acting delivery of tenofovir alafenamide (TAF) for HIV PrEP. We detail key parameters of the TAF formulation that affect implant performance, including TAF ionization form, the selection of excipient and the exposure to aqueous conditions. Both in-vitro studies and shelf stability tests demonstrate enhanced performance for TAF freebase (TAFFB) in this long-acting implant platform, as TAFFB maintains higher chemical stability than the TAF hemifumarate salt (TAFHF). We also examined the hydrolytic degradation profiles of various formulations of TAF and identified inflection points for the onset of the accelerated drug hydrolysis within the implant using a two-line model. The compositions of unstable formulations are characterized by liquid chromatography-mass spectrometry (LC-MS) and are correlated to predominant products of the TAF hydrolytic pathways. The hydrolysis rate of TAF is affected by pH and water content in the implant microenvironment. We further demonstrate the ability to substantially delay the degradation of TAF by reducing the rates of drug release and thus lowering the water ingress rate. Using this approach, we achieved sustained release of TAFFB formulations over 240 days and maintained > 93% TAF purity under simulated physiological conditions. The opportunities for optimization of TAF formulations in this biodegradable implant supports further advancement of strategies to address long-acting HIV PrEP. View Full-Text
Keywords: HIV pre-exposure prophylaxis; tenofovir alafenamide; implant; long-acting drug delivery; poly(ε-caprolactone) (PCL); biodegradable polymer HIV pre-exposure prophylaxis; tenofovir alafenamide; implant; long-acting drug delivery; poly(ε-caprolactone) (PCL); biodegradable polymer
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MDPI and ACS Style

Li, L.; Johnson, L.M.; Krovi, S.A.; Demkovich, Z.R.; van der Straten, A. Performance and Stability of Tenofovir Alafenamide Formulations within Subcutaneous Biodegradable Implants for HIV Pre-Exposure Prophylaxis (PrEP). Pharmaceutics 2020, 12, 1057. https://doi.org/10.3390/pharmaceutics12111057

AMA Style

Li L, Johnson LM, Krovi SA, Demkovich ZR, van der Straten A. Performance and Stability of Tenofovir Alafenamide Formulations within Subcutaneous Biodegradable Implants for HIV Pre-Exposure Prophylaxis (PrEP). Pharmaceutics. 2020; 12(11):1057. https://doi.org/10.3390/pharmaceutics12111057

Chicago/Turabian Style

Li, Linying, Leah M. Johnson, Sai A. Krovi, Zach R. Demkovich, and Ariane van der Straten. 2020. "Performance and Stability of Tenofovir Alafenamide Formulations within Subcutaneous Biodegradable Implants for HIV Pre-Exposure Prophylaxis (PrEP)" Pharmaceutics 12, no. 11: 1057. https://doi.org/10.3390/pharmaceutics12111057

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