Formulations

Solutions

Nebulizers have been most commonly employed to deliver solution formulations of inhaled anticancer agents. Solution formulations employed in nebulizers were not specifically prepared for inhalation and had the potential to produce local irritant effects. However, the active moiety in the solution retained efficacy after nebuliza- tion. Repeated inhalations of the intravenous (IV) formulations of cisplatinum and gemcitabine (GEM) were shown to be well tolerated in anesthetized, mechanically ventilated dogs (Selting et al. 2008, 2011). No signs of significant local or systemic toxicity were observed after administration of escalating doses of cisplatin (10, 15, 20, and 30 mg/m2 given by INC every 2 weeks for 10 weeks; cumulative dose 75 mg/m2) (Selting et al. 2008). In a follow-up study, administration of escalating doses of combination chemotherapy (GEM 1, 2, 3, or 6 mg/kg and cisplatin 10 mg/m2 given by INC every 2 weeks for 10 weeks) also did not produce clinical or biochemical side effects (Selting et al. 2011). All the dogs developed focal pneumonitis radiologically limited to the treated lobe, which increased in severity over time following increasing doses of chemotherapy. At autopsy, these radiologic changes correlated with chronic pneumonitis with fibrosis. Other investigators employed a freeze-dried powder of GEM or carboplatin solution reconstituted with normal saline for inhalation (Lemarie et al. 2011; Zarogoulidis et al. 2012). Because of problems in maintaining stability of solution formulations, many newer inhaled anticancer agents are now being formulated as dry powders, especially in an NP form.

 
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