Quality by design optimization of cold sonochemical synthesis of zidovudine-lamivudine nanosuspensions

Bwalya A. Witika, Vincent J. Smith, Roderick B. Walker*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Lamivudine (3TC) and zidovudine (AZT) are antiviral agents used to manage HIV/AIDS infection. The compounds require frequent dosing, exhibit unpredictable bioavailability and a side effect profile that includes hepato-and haema-toxicity. A novel pseudo one-solvent bottom-up approach and Design of Experiments using sodium dodecyl sulphate (SDS) and α-tocopheryl polyethylene glycol succinate 1000 (TPGS 1000) to electrosterically stablize the nano co-crystals was used to develop, produce and optimize 3TC and AZT nano co-crystals. Equimolar solutions of 3TC in surfactant dissolved in de-ionised water and AZT in methanol were rapidly injected into a vessel and sonicated at 4C. The resultant suspensions were characterized using a Zetasizer and the particle size, polydispersity index and Zeta potential determined. Optimization of the nanosuspensions was conducted using a Central Composite Design to produce nano co-crystals with specific identified and desirable Critical Quality Attributes including particle size (PS) < 1000 nm, polydispersity index (PDI) < 0.500 and Zeta potential (ZP) < −30mV. Further characterization was undertaken using Fourier Transform infrared spectroscopy, energy dispersive X-ray spectroscopy, differential scanning calorimetry, powder X-ray diffraction and transmission electron microscopy. In vitro cytotoxicity studies revealed that the optimized nano co-crystals reduced the toxicity of AZT and 3TC to HeLa cells.

Original languageEnglish
Article number367
JournalPharmaceutics
Volume12
Issue number4
DOIs
Publication statusPublished - Apr 2020
Externally publishedYes

Keywords

  • Crystal engineering
  • Design of experiments
  • HIV/AIDS
  • Lamivudine
  • Nano co-crystals
  • Quality by Design
  • Sonochemistry
  • Zidovudine

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