Two into one does go : Formulation development of a multipurpose combination vaginal ring releasing dapivirine and metronidazole for prevention of HIV infection and treatment of bacterial vaginosis
Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved..
Bacterial vaginosis (BV) is a common but often asymptomatic dysbiosis of the human vagina characterized by an imbalance in the normal vaginal microbiota due to loss of lactobacilli and an overgrowth of certain anaerobic bacteria. While BV itself is not a sexually transmitted infection, it is associated with an increased risk in women of various sexually acquired infections, including human immunodeficiency virus (HIV) infection. There is, therefore, a strong rationale for pursuing new multipurpose products that seek to treat or prevent BV alongside preventing HIV infection. With the dapivirine-releasing vaginal ring for HIV prevention now approved in several African countries, here we report formulation development of a next-generation ring product that releases both dapivirine (DPV) and the antibiotic drug metronidazole (MET). Following thermal analysis studies to characterize the phase behaviour of DPV-MET mixtures and rheological analysis to assess the cure characteristics of the active silicone elastomer mixes, matrix-type rings were manufactured containing 25 or 200 mg DPV in combination with 100, 250, 500, 1000 or 2000 mg MET. The results for drug content, in vitro release, mechanical testing, and Gardnerella vaginalis time-kill experiments demonstrate the feasibility of incorporating both DPV and MET in a matrix-type ring formulation and indicate that clinically effective release rates may be possible.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:648 |
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| Enthalten in: |
International journal of pharmaceutics - 648(2023) vom: 15. Dez., Seite 123572 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhao, Xinyu [VerfasserIn] |
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| Links: |
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| Themen: |
140QMO216E |
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| Anmerkungen: |
Date Completed 05.12.2023 Date Revised 05.12.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ijpharm.2023.123572 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM364180242 |
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| 520 | |a Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a Bacterial vaginosis (BV) is a common but often asymptomatic dysbiosis of the human vagina characterized by an imbalance in the normal vaginal microbiota due to loss of lactobacilli and an overgrowth of certain anaerobic bacteria. While BV itself is not a sexually transmitted infection, it is associated with an increased risk in women of various sexually acquired infections, including human immunodeficiency virus (HIV) infection. There is, therefore, a strong rationale for pursuing new multipurpose products that seek to treat or prevent BV alongside preventing HIV infection. With the dapivirine-releasing vaginal ring for HIV prevention now approved in several African countries, here we report formulation development of a next-generation ring product that releases both dapivirine (DPV) and the antibiotic drug metronidazole (MET). Following thermal analysis studies to characterize the phase behaviour of DPV-MET mixtures and rheological analysis to assess the cure characteristics of the active silicone elastomer mixes, matrix-type rings were manufactured containing 25 or 200 mg DPV in combination with 100, 250, 500, 1000 or 2000 mg MET. The results for drug content, in vitro release, mechanical testing, and Gardnerella vaginalis time-kill experiments demonstrate the feasibility of incorporating both DPV and MET in a matrix-type ring formulation and indicate that clinically effective release rates may be possible | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Gardnerella vaginalis | |
| 650 | 4 | |a HIV prevention | |
| 650 | 4 | |a Multipurpose prevention technology (MPT) | |
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| 700 | 1 | |a Bashi, Yahya Dallal |e verfasserin |4 aut | |
| 700 | 1 | |a Murphy, Diarmaid J |e verfasserin |4 aut | |
| 700 | 1 | |a McCoy, Clare F |e verfasserin |4 aut | |
| 700 | 1 | |a Coulter, Sophie |e verfasserin |4 aut | |
| 700 | 1 | |a Laverty, Garry |e verfasserin |4 aut | |
| 700 | 1 | |a Malcolm, R Karl |e verfasserin |4 aut | |
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