The effect of amino acid excipients on morphology and solid-state properties of multi-component spray-dried formulations for pulmonary delivery of biomacromolecules

作者：Sou Tomas; Kaminskas Lisa M; Tri Hung Nguyen; Carlberg Renee; McIntosh Michelle P^*; Morton David A V

来源：European Journal of Pharmaceutics and Biopharmaceutics, 2013, 83(2): 234-243.

DOI：10.1016/j.ejpb.2012.10.015

• Dry powder inhalers
• Spray-drying
• Pulmonary delivery
• Aerosolisation
• Particle engineering
• Molecular self-assembly

For a dry powder carrier platform to be suitable for pulmonary delivery of potent biomacromolecules, it has to be aerosolisable and capable of stabilising the biomacromolecules. In the present study, strategies aiming to produce a multi-component spray-dried powder formulation with a stable amorphous glassy matrix containing mannitol, trehalose, glycine and alanine, while using leucine as a particle formation and aerosolisation enhancing agent were investigated. The results from in vitro aerosolisation studies demonstrated high fine particle fractions (FPFs) from several formulations. Scanning electronic micrographs (SEMs) revealed distinct morphological features of these formulations in response to increasing leucine concentration: from the apparent insufficiency for discrete particle formation, to reduced particle agglomeration, to increased surface corrugation. X-ray powder diffraction (XRPD) results indicated that partially ordered leucine resulting from self-assembly on the particle surface is important for the amino acid to function effectively as an encapsulating agent. This may also play a role in inhibiting crystallisation of other components within the formulation. In conclusion, the results suggest that with suitable particle size, good dispersibility and solid-state properties, selected trehalose/leucine combinations appear to have good potential for development into a universal carrier platform for pulmonary delivery of potent biomacromolecules and the work highlights areas deserving further investigation.

• 出版日期2013-2