Efficiency of a Lyophilizate for Dry Powder Inhalation System for Drug Delivery of Ghrelin in Monkeys

Abstract

Background: A lyophilizate for dry powder inhalation (LDPI) system is unique in that its formulation, a lyophilized cake, is aerosolized just upon inhalation by convection flow of air. An LDPI system may be advantageous, especially for biopharmaceutics, such as proteins and peptides, because formulations can be manufactured without high temperature and shear stress. It was already reported that formulations of peptides used in an LDPI system showed high aerosolization performance. However, it was not confirmed whether the LDPI system could deliver drugs efficiently enough for practical use. Objective: In this study, we compared the drug delivery efficiency of an LDPI system with intravenous and subcutaneous injections. Methods: We administered LDPI formulations containing ghrelin as model formulations to monkeys and measured pharmacokinetic profiles. Results: As a result of pharmacokinetics testing in the monkeys, the relative bioavailability of an inhaled drug compared to subcutaneous injection was 24-92%. The LDPI system showed high relative bioavailability based on the fact that the relative bioavailability of inhaled insulin was 10- 30%. Conclusion: It is expected that the LDPI system can deliver drugs efficiently enough for practical use even in the systemic application of bio-pharmaceutics.