Designing a Multicomponent Spray-Dried Formulation Platform for Pulmonary Delivery of Biomacromolecules: The Effect of Polymers on the Formation of an Amorphous Matrix for Glassy State Stabilization of Biomacromolecules

Abstract

Non-reducing sugars such as mannitol are widely studied as excipients for spray-dried pharmaceutical formulations. In contrast, the present study investigated the use of a range of polymers for the production of an amorphous glassy carrier platform for pulmonary delivery of potent biomacromolecules. Two different natural polysaccharides, inulin and dextran, and the synthetic polymer polyvinylpyrrolidone (PVP) were combined with leucine using spray-drying. In addition, the effect of these polymers in combination with mannitol was studied. The results showed that leucine was a very effective particle formation agent that substantially improved processing yields of the spray-dried polymer–leucine-based formulations and formed high-rugosity particles with high fine particle fractions. The work indicated the potential utilities of these multicomponent systems as a novel dry powder formulation platform for pulmonary delivery of various biomacromolecules.

Keywords:

• Biomacromolecules
• Dry powder inhalers
• Glassy stabilization
• Polymers
• Pulmonary delivery
• Spray-drying

ACKNOWLEDGMENTS

T.S. is the recipient of Australian Postgraduate Award (APA) scholarship. L.M.K. is supported by an NHMRC Australian Biomedical Training Fellowship. The kind donations of Monodose inhalers from Miat and HPMC capsules from Capsugel are gratefully acknowledged.

Notes

n/a, not applicable; ∞, infinity.