132 Respirability assessment of amikacin from a novel dry powder inhaler versus nebulized solution

Abstract

Objectives The aim of this work was to compare in vitro the aerodynamic behavior of an amikacin sulphate liquid solution after nebulization and an amikacin dry powder (AmikaPS) after aerosolization. AmikaPS, was prepared using a proprietary spray drying technology to construct a powder to inhale having high content of drug and respirability. Methods Amikacin solution for injection was nebulized with Pari Turbo boy equipped with a Pari LC plus cup. AmikaPS powder was loaded in the DPI device (RS01, Plastiape) at the labeled dose of 125 mg of amikacin sulfate. Results The dosage of amikacin solution given off-label by nebulization is 625 mg/twice a day. At the end of the nebulization, it was found that, more than 50% of the amikacin dose (625 mg amikacin sulfate corresponding to 500 mg amikacin base) remained in the ampule, about 20% was dispersed in the environment and only 17.6% of the loaded dose was delivered as aerosol available for inhalation. Thus, since the respirable fraction of this aerosol was 56.3%, the dose to lung after 625 mg nebulization resulted 61.8 mg of amikacin sulfate. The fine particle dose of AmikaPS powder was 63.8 mg of amikacin sulfate. The data indicate that 125 mg of amikacin sulfate powder afford a respirable dose equivalent, or even slightly higher than that obtained by nebulizing 3 mL of solution for injection containing 625 mg of amikacin sulfate. Conclusions The objective of the proposed amikacin product is to offer a valid alternative to the other antibiotics for inhalation, keeping as low as possible the amount of powder to be inhaled by the patient while maximizing the amount of active ingredient deposited in the lung.