Use of a Fundamental Approach to Spray-Drying Formulation Design to Facilitate the Development of Multi-Component Dry Powder Aerosols for Respiratory Drug Delivery
- 1k Downloads
A fundamental approach incorporating current theoretical models into aerosol formulation design potentially reduces experimental work for complex formulations. A D-amino acid mixture containing D-Leucine (D-Leu), D-Methionine, D-Tryptophan, and D-Tyrosine was selected as a model formulation for this approach.
Formulation design targets were set, with the aim of producing a highly dispersible D-amino acid aerosol. Particle formation theory and a spray dryer process model were applied with boundary conditions to the design targets, resulting in a priori predictions of particle morphology and necessary spray dryer process parameters. Two formulations containing 60% w/w trehalose, 30% w/w D-Leu, and 10% w/w remaining D-amino acids were manufactured.
The design targets were met. The formulations had rugose and hollow particles, caused by deformation of a crystalline D-Leu shell while trehalose remained amorphous, as predicted by particle formation theory. D-Leu acts as a dispersibility enhancer, ensuring that both formulations: 1) delivered over 40% of the loaded dose into the in vitro lung region, and 2) achieved desired values of lung airway surface liquid concentrations based on lung deposition simulations.
Theoretical models were applied to successfully achieve complex formulations with design challenges a priori. No further iterations to the design process were required.
KEY WORDSantimicrobial D-amino acids in silico lung particle formation model spray drying
Acknowledgments and Disclosures
M. A. Boraey and R. Vehring would like to thank the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Alberta Innovates Technology Futures (AITF) for their financial support.
- 6.Boraey MA, Matinkhoo S, Vehring R. A new time and cost effective approach for the development of microparticles for pulmonary drug delivery. In: Dalby RN, Byron PR, Peart J, Suman JD, Young PM, editors. Respiratory drug delivery Europe, vol. 2. Davis Healthcare International Publishing: Berlin, Germany; 473. p. 478–2011.Google Scholar
- 28.Hoe S, Matinkhoo S, Boraey MA, Ivey JW, Shamsaddini-Shahrbabak A, Finlay WH, et al. Substitution of L-Leucine with D-Leucine in spray-dried respirable powders for control of Pseudomonas aeruginosa infection. Chapel Hill: International Society for Aerosols in Medicine (ISAM); 2013.Google Scholar
- 29.Matinkhoo S, Hoe S, Boraey MA, Shamsaddini-Shahrbabak A, Finlay WH, and Vehring R: Spray drying D-amino acids to develop respirable dry powder for the treatment of Pseudomonas aeruginosa biofilms. American Association of Pharmaceutical Scientists (AAPS) Annual Meeting and Exposition: Chicago, IL,, 2012.Google Scholar
- 45.Vehring R, Ivey JW, Williams L, Joshi V, Dwivedi S, and Lechuga-Ballesteros D: High-sensitivity analysis of crystallinity in respirable powders using low-frequency shift Raman spectrocopy. In: RN Dalby, PR Byron, J Peart, JD Suman, and PM Young, editors, Respiratory drug delivery Vol II. Davis Healthcare International Publishing; 2012. pp. 641–644.Google Scholar
- 46.Shamsaddini-Sharbabak A, Vehring R. The compression behavior of respirable powders at different relative humidity measured by a compressed bulk density tester for small sample masses. In: Dalby RN, Byron PR, Peart J, Suman JD, Young PM, editors. Respiratory drug delivery, vol. III. River Grove: Davis Healthcare International Publishing; 777. p. 780–2012.Google Scholar
- 53.Clark AR, Hollingworth AM. The relationship between powder inhaler resistance and peak inspiratory conditions in healthy volunteers – Implications for in vitro testing. J Aerosol Med. 1993;6:99–110.Google Scholar