Your browser doesn't support javascript.
loading
Physicochemical surrogates for in vitro toxicity assessment of liposomal amphotericin B.
Marx, Richard; Lee, Jaeweon; Svirkin, Yuri; Yoon, Seongkyu; Landrau, Nelson; Abul Kaisar, Md; Qin, Bin; Park, Jin H; Alam, Khondoker; Kozak, Darby; Wang, Yan; Xu, Xiaoming; Zheng, Jiwen; Rivnay, Benjamin.
Afiliación
  • Marx R; Landrau Scientific Innovations, 22 Laurel Street, Leominster, MA 01453, USA.
  • Lee J; Landrau Scientific Innovations, 22 Laurel Street, Leominster, MA 01453, USA.
  • Svirkin Y; Landrau Scientific Innovations, 22 Laurel Street, Leominster, MA 01453, USA.
  • Yoon S; Department of Chemical Engineering, University of Massachusetts Lowell, 1 University Ave, Lowell, MA, 01854, USA. Electronic address: Seongkyu_Yoon@uml.edu.
  • Landrau N; Landrau Scientific Innovations, 22 Laurel Street, Leominster, MA 01453, USA.
  • Abul Kaisar M; Food and Drug Administration, Center for Drug Evaluation and Research, Office of Generic Drugs, Office of Research and Standards, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
  • Qin B; Food and Drug Administration, Center for Drug Evaluation and Research, Office of Generic Drugs, Office of Research and Standards, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
  • Park JH; Food and Drug Administration, Center for Drug Evaluation and Research, Office of Generic Drugs, Office of Research and Standards, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
  • Alam K; Food and Drug Administration, Center for Drug Evaluation and Research, Office of Generic Drugs, Office of Research and Standards, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
  • Kozak D; Food and Drug Administration, Center for Drug Evaluation and Research, Office of Generic Drugs, Office of Research and Standards, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
  • Wang Y; Food and Drug Administration, Center for Drug Evaluation and Research, Office of Generic Drugs, Office of Research and Standards, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
  • Xu X; Food and Drug Administration, Center for Drug Evaluation and Research, Office of Pharmaceutical Quality, Office of Testing and Research, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
  • Zheng J; Food and Drug Administration, Center for Devices and Radiological Health, Office of Science and Engineering Laboratories, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
  • Rivnay B; Landrau Scientific Innovations, 22 Laurel Street, Leominster, MA 01453, USA.
Int J Pharm ; 628: 122273, 2022 Nov 25.
Article en En | MEDLINE | ID: mdl-36228881
ABSTRACT
Pharmaceutical toxicity evaluations often use in vitro systems involving primary cells, cell lines or red blood cells (RBCs). Cell-based analyses ('bioassays') can be cumbersome and typically rely on hard-to-standardize biological materials. Amphotericin B (AmB) toxicity evaluations are primarily based on potassium release from RBCs and share these limitations. This study evaluates the potential substitution of two physicochemical AmB toxicity approaches for the bioassay Ultraviolet-visible spectroscopy (UV-vis) and in vitro drug release kinetics. UV-vis spectral analyses indicated that liposomal AmB's (L-AmB) main peak position (λmax) and peak ratio (OD346/OD322) are potential toxicity surrogates. Similarly, two first-order release parameters derived from USP-4 in vitro drug release analyses also provided linear relationships with toxicity. These were the initial, overall drug release rate and the ratio of loose to tight AmB pools. Positive slopes and high correlation coefficients (R2 > 0.9) characterized all interrelations between physicochemical parameters and toxicity. These tests converted the manufacturing variables' nonlinear (i.e., curvilinear) relationships with in vitro toxicity to linear responses. Three different toxicity attenuation approaches (2 manufacturing, 1 formulation), covering formulation composition and process aspects, support this approach's universality. These data suggest that one or more spectral and kinetic physicochemical tests can be surrogates for L-AmB in vitro toxicity testing.
Asunto(s)
Palabras clave
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Anfotericina B / Antifúngicos Idioma: En Revista: Int J Pharm Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Anfotericina B / Antifúngicos Idioma: En Revista: Int J Pharm Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos