Elucidation of the using condition and working mechanism of tertiary lactose in dry powder formulations for inhalation

Abstract

Tertiary lactose has been shown to improve aerosolization performance of carrier-based dry powder inhalation formulations. The working mechanism of the tertiary lactose, however, is still unclear, even the optimal working condition of the lactose fines. Two strategies to incorporate the tertiary lactose were proposed, the “tertiary lactose-carrier-API” and “tertiary lactose-API-carrier”, to decrease the adhesiveness of the drug-carrier by forming different powder aggregates. The effects of the tertiary lactose with different sizes and mass percentages on the aerosolization performance for the two types of formulations were systemically investigated. The results showed that the smaller-sized tertiary lactose is beneficial for powder dispersion and aerosolization, which could be further improved by optimizing its concentration. In terms of the aerosolization performance, the “tertiary lactose-carrier-API” type of ternary formulations obtained highly superior aerosolization performance and significantly enhanced detachment of fine drug particles from large particles in general.