A silicone elastomer vaginal ring for HIV prevention containing two microbicides with different mechanisms of action.
Eur J Pharm Sci
; 48(3): 406-15, 2013 Feb 14.
Article
em En
| MEDLINE
| ID: mdl-23266465
ABSTRACT
Vaginal rings are currently being developed for the long-term (at least 30 days) continuous delivery of microbicides against human immunodeficiency virus (HIV). Research to date has mostly focused on devices containing a single antiretroviral compound, exemplified by the 25mg dapivirine ring currently being evaluated in a Phase III clinical study. However, there is a strong clinical rationale for combining antiretrovirals with different mechanisms of action in a bid to increase breadth of protection and limit the emergence of resistant strains. Here we report the development of a combination antiretroviral silicone elastomer matrix-type vaginal ring for simultaneous controlled release of dapivirine, a non-nucleoside reverse transcriptase inhibitor, and maraviroc, a CCR5-targeted HIV-1 entry inhibitor. Vaginal rings loaded with 25mg dapivirine and various quantities of maraviroc (50-400mg) were manufactured and in vitro release assessed. The 25mg dapivirine and 100mg maraviroc formulation was selected for further study. A 24-month pharmaceutical stability evaluation was conducted, indicating good product stability in terms of in vitro release, content assay, mechanical properties and related substances. This combination ring product has now progressed to Phase I clinical testing.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pirimidinas
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Elastômeros de Silicone
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Triazóis
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Sistemas de Liberação de Medicamentos
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Inibidores da Transcriptase Reversa
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Dispositivos Anticoncepcionais Femininos
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Cicloexanos
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Antagonistas dos Receptores CCR5
Idioma:
En
Revista:
Eur J Pharm Sci
Assunto da revista:
FARMACIA
/
FARMACOLOGIA
/
QUIMICA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Reino Unido