Thin-film freeze-drying technology for nasal and pulmonary drug delivery

Thin-film freeze-drying creates stable, porous dry powders for nasal and lung delivery of sensitive drugs like vaccines and antibodies. This preserves their activity, targets specific respiratory areas, enhances storage, and effectively treats respiratory infections such as COVID-19.

Background

Respiratory drug delivery is a vital area in pharmaceutical technology, focusing on administering medications directly to the nasal passages or lungs. This approach offers numerous advantages, including rapid onset of action, targeted delivery to specific regions of the respiratory tract, and the potential for both local and systemic therapeutic effects. With the increasing prevalence of respiratory infections such as influenza, RSV, and COVID-19, there is a growing demand for effective delivery systems for vaccines and biologic therapeutics. Additionally, the stability of sensitive therapeutic agents during storage and their ability to maintain biological activity upon administration are critical factors in addressing these health challenges.

However, current approaches to respiratory drug delivery encounter significant obstacles. Traditional liquid formulations often suffer from stability issues, especially for sensitive biologics like vaccines, monoclonal antibodies, and mRNA therapies. Ensuring consistent and efficient delivery to targeted areas within the respiratory tract is challenging with existing devices and formulations, leading to uneven distribution and suboptimal therapeutic outcomes. Liquid sprays, for instance, can result in limited residence time in target tissues and reduced efficacy.

Moreover, conventional processing methods that involve high shear forces or elevated temperatures can degrade the biological activity of delicate therapeutics, compromising their effectiveness. These limitations highlight the need for advanced formulation techniques that enhance stability, improve targeted delivery, and preserve the integrity of sensitive pharmaceutical agents.

Technology description

This technology utilizes thin-film freeze-drying (TFFD) to produce dry powder pharmaceutical formulations tailored for nasal and pulmonary delivery. The process begins by dissolving or dispersing an active pharmaceutical ingredient—such as vaccines, monoclonal antibodies, nucleic acids, or mRNA-lipid nanoparticles—with primary excipients like sugars or amino acids and mucoadhesive excipients like chitosan or sodium alginate in a suitable solvent. The mixture is rapidly frozen on a cryogenically cooled surface and then subjected to primary and secondary lyophilization stages, resulting in a highly porous and brittle powder.

These formulations are engineered for deep lung delivery using low-concentration feedstocks or for intranasal delivery with higher concentrations and specialized delivery devices that achieve high initial velocities. This approach enhances pharmaceutical stability during storage, extends residence time in target tissues, and enables efficient delivery to specific regions within the respiratory tract, making it ideal for treating respiratory infections such as influenza, RSV, and COVID‑19.

What sets this technology apart is its innovative application of TFFD, which ensures the preservation of sensitive biologics by minimizing shear and heat stress during processing. The creation of highly porous powders optimized for respiratory administration allows for both deep lung and targeted intranasal delivery, catering to diverse therapeutic needs. Additionally, the versatility in formulation components, including a wide range of active ingredients and excipients, supports the development of stable and effective dry powders without the need for reconstitution before administration. The ability to generate both systemic and mucosal immune responses, coupled with demonstrated effectiveness in maintaining biological activity and precise deposition patterns, underscores the technology’s unique advantage in delivering complex therapeutics efficiently and reliably to the respiratory system.

Benefits

Increased stability of pharmaceuticals during storage
Preservation of biological activity of sensitive therapeutics
Enhanced delivery efficiency to specific regions of the respiratory tract
Improved residence time in target tissues
Versatility for delivering various therapeutics, including vaccines and antibodies
Direct administration capability without the need for reconstitution
Effective treatment of respiratory infections such as influenza, RSV, and COVID-19