Formulation development and in vivo evaluation of a new dry powder formulation of albuterol sulphate in beagle dogs.

PURPOSE

Study objectives were to develop, characterize, and evaluate a novel excipient for dry powder inhalation formulations in a canine model with a model compound.

METHODS

Dry powder inhalation formulations of albuterol sulphate were developed and compared to a commercially available nebulizer albuterol solution formulation. In vitro analysis indicated a high fine-particle fraction (FPF, >70%) and a respirable particle size ( approximately 2.5 microm MMAD). Each inhalation formulation, including controls, was delivered targeting a deposited lung dose of 10 microg/kg albuterol. Active formulations were evaluated for pharmacokinetic (PK) profile and bronchodilatory effects in a ragweed-sensitized dog model of allergic airway responses.

RESULTS

In vitro, the dextran spray-dried formulated materials showed that aerosol performance, including FPF, MMAD, glass transition temperature, and amorphous characteristics, were all largely unaffected by amount of drug loaded. Both the commercial and the dry powder formulations attenuated the ragweed-induced bronchoconstriction by 91.59 +/- 3.60 and 81.28 +/- 9.29%, respectively. The PK profiles for both albuterol formulations were similar, as were the corresponding T(max), C(max) and T(1/2).

CONCLUSIONS

Results indicate that dextran 10 has promise as a novel excipient for dry powder inhalation drug delivery, in a preclinical setting, over a wide range of drug loadings.