Photoinduced particulate matter in a parenteral formulation for bisnafide, an experimental antitumor agent.

Abstract:

:This paper assesses the cause of particulate formation in vials of the experimental antitumor agent bisnafide and investigates pharmaceutical techniques to reduce the number of particulates in the product. Solution preparation and particulate isolation were performed under Class 100 laminar air flow. Reversed-phase HPLC and infrared microscopy were used to characterize drug and isolated particulate matter, whereas a Hiac particle counter was used to quantify the particulate matter. Particulate matter was observed following agitation of the drug solutions and was found to be associated with specific lots of drug substance. HPLC of the isolated particulate matter indicated that the particulates consisted largely of bisnafide and impurities that were identified as the products of photodegradation, confirmed to be the result of the photolytic cleavage of bisnafide to form a poorly soluble aldehyde. The aldehyde may, in turn, interact with bisnafide molecules to form the particulate matter as suggested by the observed pH-dependent reversibility of the particulate phenomenon. The particulate matter could be reduced by protecting solutions of bisnafide from light during chemical synthesis and production of the dosage form and, alternatively, by reducing the solution pH to 3.0 or less, addition of surfactants below their critical micelle concentration, and removal of impurities by froth flotation of the bisnafide solutions.

journal_name

Pharm Dev Technol

authors

Rubino JT,Chan LL,Walker JT,Segretario J,Everlof JG,Hussain MA

doi

10.1081/pdt-100101380

subject

Has Abstract

pub_date

1999-08-01 00:00:00

pages

439-47

issue

3

eissn

1083-7450

issn

1097-9867

journal_volume

4

pub_type

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