THE USE OF A NEW LASER PARTICLE SIZER AND SHAPE-ANALYZER TO DETECT AND EVALUATE GELATINOUS MICROPARTICLES SUSPENDED IN RECONSTITUTED ANTHRACYCLINE INFUSION SOLUTIONS

The anthracyclines are an important group of antitumour drugs; the best known anthracyclines are doxorubicin (Adriamycin(R)) and epirubicin (Pharmorubicin(R)), both of which are very active against a wide range of solid tumours and haematological malignancies. They are marketed as lyophilized formulations that need to be reconstituted for administration with water for injections or sodium chloride injection. With the aim of reducing the risks of contamination during reconstitution (spillage, spray formation, etc.) and of enhancing the rate of dissolution (that is otherwise slow because of the formation of conglomerates and gelatinous masses), a new formulation (rapid dissolution formula, RDF) containing parabens (hydroxybenzoate esters) as anti-aggregants has been developed; the formulation is a freeze-dried product and is characterized by a practically instantaneous and complete reconstitution. A valid estimate of the completeness of dissolution has been objectively achieved by means of an instrument (Galai CIS-1) that acts both as a particle sizer and a shape analyser; the instrument is equipped with a rotating laser system that defines a toroidal-cylindrical space inside the solution in which every moving particle is measured and, at the same time, visualized on a monitor by an electronically driven video microscope. The instrument has been applied with very satisfactory results to the visualization of the reconstitutional behaviour of commercial lots of Adriamycin and Pharmorubicin lyophilized products, reconstituted at a concentration of 2 mg ml-1 with sodium chloride injection.