Characterization of metal-ion-nucleotide based particulate matter in solutions of 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA)

The antiviral drug 9-[2-(phosphonomethoxy)ethyl]adenine, PMEA, was developed as an intravenous product for the treatment of human immunodeficiency virus infection. During the course of stability monitoring, PMEA i.v. injection was found to undergo particulate matter formation under extended storage...

Full description

Saved in:
Bibliographic Details
Published inPDA journal of pharmaceutical science and technology Vol. 51; no. 1; p. 30
Main Authors Yuan, L C, Visor, G C
Format Journal Article
LanguageEnglish
Published United States 01.01.1997
Subjects
Adenine - analogs & derivatives
Adenine - chemistry
Antiviral Agents - chemistry
Drug Stability
Iron - analysis
Organophosphonates
Solutions
Zinc - analysis
Online AccessGet more information

Cover

More Information
Summary:The antiviral drug 9-[2-(phosphonomethoxy)ethyl]adenine, PMEA, was developed as an intravenous product for the treatment of human immunodeficiency virus infection. During the course of stability monitoring, PMEA i.v. injection was found to undergo particulate matter formation under extended storage at ambient temperature. Isolation and characterization of the particulates revealed them to be metal ion-PMEA complexes. The principle metal ions associated with the particulates were iron and zinc, present as trace impurities (< or = 40 ppm) in PMEA drug substance determined by inductively coupled argon plasma spectroscopy. These visible particles are characterized by energy-dispersive x-ray spectrometry and fourier transform infrared spectroscopy. This study describes the systematic evaluation of the observed solution phenomena and details alternative formulation systems to eliminate particulate formation in the PMEA injectable product.
ISSN:1079-7440