Top-Down Synthesis of a Lamivudine-Zidovudine Nano Co-Crystal
Lamivudine (3TC) and zidovudine (AZT) are antiretroviral agents used to manage HIV/AIDS infection. A wet media milling top-down approach was used to develop and produce nano co-crystals of 3TC and AZT. Micro co-crystals were prepared by solvent evaporation and subsequently milled in the presence of...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | Crystals |
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| Online Access: | https://www.mdpi.com/2073-4352/11/1/33 |
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| author | Bwalya A. Witika Vincent J. Smith Roderick B. Walker |
| author_facet | Bwalya A. Witika Vincent J. Smith Roderick B. Walker |
| author_sort | Bwalya A. Witika |
| collection | DOAJ |
| description | Lamivudine (3TC) and zidovudine (AZT) are antiretroviral agents used to manage HIV/AIDS infection. A wet media milling top-down approach was used to develop and produce nano co-crystals of 3TC and AZT. Micro co-crystals were prepared by solvent evaporation and subsequently milled in the presence of two surfactants, viz., sodium lauryl sulfate (SLS) and α-tocopheryl polyethylene glycol succinate 1000 (TPGS 1000). Optimisation was undertaken using design of experiments (DoE) and response surface methodology (RSM) to establish and identify parameters that may affect the manufacturing of nano co-crystals. The impact of SLS and TPGS 1000 concentration, milling time, and number of units of milling medium on the manufacturing of nano co-crystals, was investigated. The critical quality attributes (CQA) monitored were particle size (PS), Zeta potential (ZP), and polydispersity index (PDI). Powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, transmission electron microscopy, energy dispersive X-ray spectroscopy scanning electron microscopy, and cytotoxicity assays were used for additional characterization of the optimised nano co-crystal. The mean PS, PDI, and ZP of the optimised top-down nanocrystal were 271.0 ± 92.0 nm, 0.467 ± 0.073, and −41.9 ± 3.94 mV, respectively. In conclusion, a simple, inexpensive, rapid, and precise method of nano co-crystal manufacturing was developed, validated, and optimised using DoE and RSM, and the final product exhibited the target CQA. |
| first_indexed | 2024-03-10T13:39:07Z |
| format | Article |
| id | doaj.art-d41f778c57cf4f27aecdf0994eb89151 |
| institution | Directory Open Access Journal |
| issn | 2073-4352 |
| language | English |
| last_indexed | 2024-03-10T13:39:07Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Crystals |
| spelling | doaj.art-d41f778c57cf4f27aecdf0994eb891512023-11-21T03:11:30ZengMDPI AGCrystals2073-43522020-12-011113310.3390/cryst11010033Top-Down Synthesis of a Lamivudine-Zidovudine Nano Co-CrystalBwalya A. Witika0Vincent J. Smith1Roderick B. Walker2Division of Pharmaceutics, Faculty of Pharmacy, Rhodes University, Makhanda 6140, South AfricaDepartment of Chemistry, Faculty of Science, Rhodes University, Makhanda 6140, South AfricaDivision of Pharmaceutics, Faculty of Pharmacy, Rhodes University, Makhanda 6140, South AfricaLamivudine (3TC) and zidovudine (AZT) are antiretroviral agents used to manage HIV/AIDS infection. A wet media milling top-down approach was used to develop and produce nano co-crystals of 3TC and AZT. Micro co-crystals were prepared by solvent evaporation and subsequently milled in the presence of two surfactants, viz., sodium lauryl sulfate (SLS) and α-tocopheryl polyethylene glycol succinate 1000 (TPGS 1000). Optimisation was undertaken using design of experiments (DoE) and response surface methodology (RSM) to establish and identify parameters that may affect the manufacturing of nano co-crystals. The impact of SLS and TPGS 1000 concentration, milling time, and number of units of milling medium on the manufacturing of nano co-crystals, was investigated. The critical quality attributes (CQA) monitored were particle size (PS), Zeta potential (ZP), and polydispersity index (PDI). Powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, transmission electron microscopy, energy dispersive X-ray spectroscopy scanning electron microscopy, and cytotoxicity assays were used for additional characterization of the optimised nano co-crystal. The mean PS, PDI, and ZP of the optimised top-down nanocrystal were 271.0 ± 92.0 nm, 0.467 ± 0.073, and −41.9 ± 3.94 mV, respectively. In conclusion, a simple, inexpensive, rapid, and precise method of nano co-crystal manufacturing was developed, validated, and optimised using DoE and RSM, and the final product exhibited the target CQA.https://www.mdpi.com/2073-4352/11/1/33nano co-crystalslamivudinezidovudineHIV/AIDSnano wet media millingquality by design |
| spellingShingle | Bwalya A. Witika Vincent J. Smith Roderick B. Walker Top-Down Synthesis of a Lamivudine-Zidovudine Nano Co-Crystal Crystals nano co-crystals lamivudine zidovudine HIV/AIDS nano wet media milling quality by design |
| title | Top-Down Synthesis of a Lamivudine-Zidovudine Nano Co-Crystal |
| title_full | Top-Down Synthesis of a Lamivudine-Zidovudine Nano Co-Crystal |
| title_fullStr | Top-Down Synthesis of a Lamivudine-Zidovudine Nano Co-Crystal |
| title_full_unstemmed | Top-Down Synthesis of a Lamivudine-Zidovudine Nano Co-Crystal |
| title_short | Top-Down Synthesis of a Lamivudine-Zidovudine Nano Co-Crystal |
| title_sort | top down synthesis of a lamivudine zidovudine nano co crystal |
| topic | nano co-crystals lamivudine zidovudine HIV/AIDS nano wet media milling quality by design |
| url | https://www.mdpi.com/2073-4352/11/1/33 |
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