SPRAY-DRIED solid inhalable N-acetylcysteine microparticles: Preparation and mucolytic activity testing

SPRAY-DRIED solid inhalable N-acetylcysteine microparticles: Preparation and mucolytic activity testing

Článek WoS

Inhalation is the preferred administration for treating pulmonary disorders like cystic fibrosis, with the use of mucolytics such as N-acetylcysteine being the main therapeutic strategy. This study aimed to develop spray-dried inhalable microparticles, using N-acetylcysteine and mannitol as a carrier and osmotic agent. Various methodologies were assessed to optimize the spray drying process, including different drying conditions and additives in the dispersion. The results demonstrated the requirements for particular excipients to formulate N-acetylcysteine-mannitol inhalable microparticles by spray drying. Incorporating a neutralizing agent (sodium hydroxide) or glass transition temperature modifiers (dextran, maltodextrin, chitosan) produced spherical primary particles that readily agglomerated into large clusters. Leucine, as an antiadherent agent, demonstrated efficacy as the sole excipient at a concentration of 20-25 %, facilitating the formulation of particles with appropriate size, shape, and morphology. Inhalable particles (mass median aerodynamic diameter 5.95 +/- 1.53 mu m, fine particle fraction 33.06 %) were prepared by modifying process parameters (nozzle size reduction, feed solution dilution). The encapsulated N-acetylcysteine also showed sustained mucolytic activity in vitro (35.3 % viscosity reduction after 120 min), using an innovative method. This work represents the complex study of N-acetylcysteine inhalable microparticles preparation as a possible approach to overcome liquid formulation.

Inhalation is the preferred administration for treating pulmonary disorders like cystic fibrosis, with the use of mucolytics such as N-acetylcysteine being the main therapeutic strategy. This study aimed to develop spray-dried inhalable microparticles, using N-acetylcysteine and mannitol as a carrier and osmotic agent. Various methodologies were assessed to optimize the spray drying process, including different drying conditions and additives in the dispersion. The results demonstrated the requirements for particular excipients to formulate N-acetylcysteine-mannitol inhalable microparticles by spray drying. Incorporating a neutralizing agent (sodium hydroxide) or glass transition temperature modifiers (dextran, maltodextrin, chitosan) produced spherical primary particles that readily agglomerated into large clusters. Leucine, as an antiadherent agent, demonstrated efficacy as the sole excipient at a concentration of 20-25 %, facilitating the formulation of particles with appropriate size, shape, and morphology. Inhalable particles (mass median aerodynamic diameter 5.95 +/- 1.53 mu m, fine particle fraction 33.06 %) were prepared by modifying process parameters (nozzle size reduction, feed solution dilution). The encapsulated N-acetylcysteine also showed sustained mucolytic activity in vitro (35.3 % viscosity reduction after 120 min), using an innovative method. This work represents the complex study of N-acetylcysteine inhalable microparticles preparation as a possible approach to overcome liquid formulation.

Spray drying, N-acetylcysteine, Microparticles, Dry powders, Pulmonary drug delivery

Spray drying, N-acetylcysteine, Microparticles, Dry powders, Pulmonary drug delivery

HORAVOVA, H.; PESTALOVA, A.; PAVLOKOVA, S.; KÁNSKÁ, J.; LÍZAL, F.; GAJDZIOK, J.

2026

01.12.2025

Journal of drug delivery science and technology

114

Nizozemsko

1

14

14

https://www.sciencedirect.com/science/article/pii/S1773224725010251?pes=vor&utm_source=clarivate&getft_integrator=clarivate