Aqueous Dissolution and Dispersion Behavior of Polyvinylpyrrolidone Vinyl Acetate-based Amorphous Solid Dispersion of Ritonavir Prepared by Hot-Melt Extrusion with and without Added Surfactants
Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved..
In this study, the lack of complete drug release from amorphous solid dispersions (ASDs), as observed in most published reports, was investigated. ASDs with 20% ritonavir were prepared by HME using polyvinylpyrrolidone vinyl acetate (PVPVA) alone and in combination with 10% poloxamer 407 or Span 20 as carriers. It was established by the film casting technique that ritonavir was molecularly dispersed in formulations, and accelerated stability testing confirmed that extrudates were physically stable. Dissolution of ASDs (100-mg ritonavir equivalent) was performed in 250 mL 0.01 N HCl (pH 2), pH 6.8 phosphate buffer and FeSSIF-V2. Drug concentrations were measured by filtration through 0.45-μm pores and in unfiltered media; the latter gave total amounts of drug present in dissolution media, both as solution and dispersion. Because of low solubility, ritonavir did not dissolve completely in aqueous media. Rather, it formed supersaturated solutions, and the excess drug dispersed in the oily amorphous form with low particle sizes that could crystallize with time. Due to higher drug solubility, the dissolved drug in FeSSIF-V2 was much higher than that in the phosphate buffer. Complete drug release could be observed by accounting for drug both in solution and as phase-separated dispersion. Thus, the present study provides a complete picture of in vitro drug dissolution and dispersion from ASDs.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:110 |
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| Enthalten in: |
Journal of pharmaceutical sciences - 110(2021), 4 vom: 15. Apr., Seite 1480-1494 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Siriwannakij, Nitprapa [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 17.06.2021 Date Revised 17.06.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.xphs.2020.08.007 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM314011323 |
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| 520 | |a Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a In this study, the lack of complete drug release from amorphous solid dispersions (ASDs), as observed in most published reports, was investigated. ASDs with 20% ritonavir were prepared by HME using polyvinylpyrrolidone vinyl acetate (PVPVA) alone and in combination with 10% poloxamer 407 or Span 20 as carriers. It was established by the film casting technique that ritonavir was molecularly dispersed in formulations, and accelerated stability testing confirmed that extrudates were physically stable. Dissolution of ASDs (100-mg ritonavir equivalent) was performed in 250 mL 0.01 N HCl (pH 2), pH 6.8 phosphate buffer and FeSSIF-V2. Drug concentrations were measured by filtration through 0.45-μm pores and in unfiltered media; the latter gave total amounts of drug present in dissolution media, both as solution and dispersion. Because of low solubility, ritonavir did not dissolve completely in aqueous media. Rather, it formed supersaturated solutions, and the excess drug dispersed in the oily amorphous form with low particle sizes that could crystallize with time. Due to higher drug solubility, the dissolved drug in FeSSIF-V2 was much higher than that in the phosphate buffer. Complete drug release could be observed by accounting for drug both in solution and as phase-separated dispersion. Thus, the present study provides a complete picture of in vitro drug dissolution and dispersion from ASDs | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Amorphous solid dispersion | |
| 650 | 4 | |a Dispersion | |
| 650 | 4 | |a Dissolution | |
| 650 | 4 | |a Melt extrusion | |
| 650 | 4 | |a Miscibility | |
| 650 | 4 | |a Particle size | |
| 650 | 4 | |a Phase separation | |
| 650 | 4 | |a Polyvinylpyrrolidone vinyl acetate | |
| 650 | 4 | |a Ritonavir | |
| 650 | 4 | |a Stability | |
| 650 | 7 | |a Surface-Active Agents |2 NLM | |
| 650 | 7 | |a Vinyl Compounds |2 NLM | |
| 650 | 7 | |a Povidone |2 NLM | |
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| 650 | 7 | |a vinyl acetate |2 NLM | |
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| 650 | 7 | |a Ritonavir |2 NLM | |
| 650 | 7 | |a O3J8G9O825 |2 NLM | |
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| 700 | 1 | |a Serajuddin, Abu T M |e verfasserin |4 aut | |
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