Development of inhalable dry powder formulation of basic fibroblast growth factor.

Basic fibroblast growth factor (bFGF) is a promising agent for therapy of asthma or chronic obstructive pulmonary disease. We aim to develop an inhalable powder formulation of bFGF, which may provide a safe, effective, and convenient way of delivering bFGF to the disease-ridden lungs. Development of a bFGF dry powder formulation is constrained by the poor stability of bFGF and the uncertainty in compatibility of the protein with carrier excipients. With these constraints in mind, we prepared dry powders containing bFGF in combinations of albumin, phospholipid, lactose, and/or leucine, by spray drying, and evaluated the aerodynamic properties of the powders and the stability of bFGF loaded in the powders. While an ethanolic solution of phospholipid, albumin, and lactose produced dispersible powder, bFGF was unstable in ethanol. The stability of bFGF was preserved when spray-dried with lactose in an aqueous solution. Leucine was required to obtain dry powder with good dispersibility; however, increase in the leucine content more than 50% (w/w) negatively influenced the bFGF stability with no additional benefit to the aerodynamic properties of the powders. Dry powders containing 20% (w/w) leucine provided desirable aerodynamic properties (fine particle fraction of 25.2+/-5.4% and mass median aerodynamic diameter of 4.7+/-0.9 microm) and 98.1+/-7% recovery of bioactive bFGF. This result warrants further investigation of the biological activity of the inhaled bFGF in a disease model.