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Impact of excipient choice on the aerodynamic performance of inhalable spray-freeze-dried powders.
Int J Pharm. 2020 Aug 30; 586:119564.IJ

Abstract

Spray-freeze-drying (SFD) is a process in which a solution is dispersed into a freezing medium and dried by sublimation, resulting in lyophilized powders with spherical particles. This study aims at screening and evaluating the impact of the excipient choice and spray solution characteristics in SFD on the physico-chemical characteristics of lyospheres and rate their suitability for producing pulmonary applicable powders using a novel SFD method. A monodisperse droplet-stream was injected into a vortex of cold gas for the production of inhalable, uniform spherical lyophilisates with a narrow particle size distribution. Model solutions containing graded contents (0.3%, 1.0%, and 3.0% w/v) of common bulk-forming excipients like mannitol, lactose, poylvinylpyrrolidone (PVP), maltodextrin or hydroyxpropyl methylcellulose (HPMC) and their blends were dispersed using a single 20 μm pinhole diaphragm. Powders were analyzed regarding their geometric particle size, apparent density, mechanical stability and aerodynamic performance. The diameter of the frozen droplets partially correlated with the Ohnesorge number of the spray solutions. The lyosphere powders had median geometric particle diameters ranging from 20 µm to 81 µm. Some powders showed signs of particle shrinkage during the drying step and diameters were reduced down to 30% of their initial size. The apparent particle densities ranged from 0.009 g/cm3 to 0.087 g/cm3. The mechanical stability of the lyospheres depended on the constituents and concentration of the initial spray solution. Mannitol/maltodextrin formulations yielded large porous particles with promising performance in the Next-Generation-Impactor, emitted fractions between 92 and 98% (w/w) and fine-particle-fractions of over 55% (w/w). According to our first steps towards formulations for free-flowing inhalable spray freeze-dried powders the impact of excipient choice on the SFD process is significant and based on the current findings we consider mannitol or mannitol/maltodextrin as best performing formulations.

Authors+Show Affiliations

Department of Pharmaceutics, Institute of Pharmacy, University of Bonn, Bonn, Germany.Department of Pharmaceutics, Institute of Pharmacy, University of Bonn, Bonn, Germany.Department of Pharmaceutics, Institute of Pharmacy, University of Bonn, Bonn, Germany; PEPITE (EA4267), University of Burgundy/Franche-Comté, Besançon, France. Electronic address: alf.lamprecht@uni-bonn.de.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32590097

Citation

Wanning, Stefan, et al. "Impact of Excipient Choice On the Aerodynamic Performance of Inhalable Spray-freeze-dried Powders." International Journal of Pharmaceutics, vol. 586, 2020, p. 119564.
Wanning S, Süverkrüp R, Lamprecht A. Impact of excipient choice on the aerodynamic performance of inhalable spray-freeze-dried powders. Int J Pharm. 2020;586:119564.
Wanning, S., Süverkrüp, R., & Lamprecht, A. (2020). Impact of excipient choice on the aerodynamic performance of inhalable spray-freeze-dried powders. International Journal of Pharmaceutics, 586, 119564. https://doi.org/10.1016/j.ijpharm.2020.119564
Wanning S, Süverkrüp R, Lamprecht A. Impact of Excipient Choice On the Aerodynamic Performance of Inhalable Spray-freeze-dried Powders. Int J Pharm. 2020 Aug 30;586:119564. PubMed PMID: 32590097.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impact of excipient choice on the aerodynamic performance of inhalable spray-freeze-dried powders. AU - Wanning,Stefan, AU - Süverkrüp,Richard, AU - Lamprecht,Alf, Y1 - 2020/06/23/ PY - 2020/01/23/received PY - 2020/06/17/revised PY - 2020/06/18/accepted PY - 2020/6/27/pubmed PY - 2020/6/27/medline PY - 2020/6/27/entrez KW - Droplet collision KW - Droplet-stream generator KW - Lyophilization KW - Lyosphere KW - Porous particles KW - Protein formulations KW - Pulmonary drug delivery KW - Spray freeze drying SP - 119564 EP - 119564 JF - International journal of pharmaceutics JO - Int J Pharm VL - 586 N2 - Spray-freeze-drying (SFD) is a process in which a solution is dispersed into a freezing medium and dried by sublimation, resulting in lyophilized powders with spherical particles. This study aims at screening and evaluating the impact of the excipient choice and spray solution characteristics in SFD on the physico-chemical characteristics of lyospheres and rate their suitability for producing pulmonary applicable powders using a novel SFD method. A monodisperse droplet-stream was injected into a vortex of cold gas for the production of inhalable, uniform spherical lyophilisates with a narrow particle size distribution. Model solutions containing graded contents (0.3%, 1.0%, and 3.0% w/v) of common bulk-forming excipients like mannitol, lactose, poylvinylpyrrolidone (PVP), maltodextrin or hydroyxpropyl methylcellulose (HPMC) and their blends were dispersed using a single 20 μm pinhole diaphragm. Powders were analyzed regarding their geometric particle size, apparent density, mechanical stability and aerodynamic performance. The diameter of the frozen droplets partially correlated with the Ohnesorge number of the spray solutions. The lyosphere powders had median geometric particle diameters ranging from 20 µm to 81 µm. Some powders showed signs of particle shrinkage during the drying step and diameters were reduced down to 30% of their initial size. The apparent particle densities ranged from 0.009 g/cm3 to 0.087 g/cm3. The mechanical stability of the lyospheres depended on the constituents and concentration of the initial spray solution. Mannitol/maltodextrin formulations yielded large porous particles with promising performance in the Next-Generation-Impactor, emitted fractions between 92 and 98% (w/w) and fine-particle-fractions of over 55% (w/w). According to our first steps towards formulations for free-flowing inhalable spray freeze-dried powders the impact of excipient choice on the SFD process is significant and based on the current findings we consider mannitol or mannitol/maltodextrin as best performing formulations. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/32590097/Impact_of_excipient_choice_on_the_aerodynamic_performance_of_inhalable_spray-freeze-dried_powders L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(20)30548-2 DB - PRIME DP - Unbound Medicine ER -
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