Excipients for respiratory delivery play a vital role in helping the pharmaceutical industry deliver complex biologic drugs such as proteins, peptides, and nucleic acids safely and effectively. They stabilise delicate molecules, enhance formulation performance, and ensure consistent dosing through inhalation.
As biologic therapies become more advanced, selecting the right delivery method and formulation components has never been more important. In this Q&A, KC experts explain how the right excipients can improve stability, manufacturability, and regulatory success in biologic inhalation formulation.
What is the role of excipients in the respiratory delivery of biologics (proteins, peptides, nucleic acids)?
Excipients stabilize and protect biologic drugs during respiratory delivery. They improve formulation performance, manufacturing efficiency, and patient safety. Excipients, all inactive formulation components beyond the API, are fundamental to the success of inhaled biotherapeutics.
For any biologic inhalation formulation, excipients are essential for three main reasons:
- API Stability: They maintain the API’s three-dimensional structure, protecting it from physical degradation (such as aggregation) and chemical degradation (such as oxidation) during manufacturing and storage.
- Efficacy and Performance: They ensure the formulation meets necessary physical characteristics, such as optimal viscosity and surface tension in liquid forms, or good aerosol performance in dry powder forms.
- Manufacturability and Safety: They assist in processing and help preserve sterility in multidose liquid formulations while also simplifying the path to regulatory approval.
Why is the choice of excipients so critical early in the development of an inhaled biologic?
Selecting suitable excipients early ensures efficient development, product stability, and a smoother regulatory approval process.
The choice of excipient directly affects a therapeutic’s manufacturability, stability, and performance. Because the formulation and the delivery device (for example, a nebuliser or inhaler) must be developed in parallel, early excipient selection is key to avoiding compatibility issues and costly delays. Our best advice: adopt a “less is more” approach. Only include excipients that demonstrably maximise therapeutic effect and minimise potential incompatibility issues, helping to streamline inhaled biotherapeutic development.
What are the three key classes of excipients used in inhalation therapies?
Inhaled formulations typically rely on three classes of excipients to optimise API stability, consistency, and delivery performance.
| Excipient Class | Common Examples | Primary Function |
|---|---|---|
| Buffering Systems and Salts | Sodium phosphate, Sodium chloride | Enhance the physical and chemical stability of the API. |
| Surfactants | Polysorbate 80, Poloxamer 188 | Minimise API aggregation and prevent interfacial adsorption. |
| Stabilisers / Bulking Agents | Sucrose, Mannitol, Trehalose | Maintain API structure in both liquid and solid-state forms, especially during drying (lyophilisation). |
What are the unique challenges and solutions for developing excipients for a solid dosage form (dry powder)?
Maintaining API stability and aerosol performance in dry powder form is one of the biggest challenges in biologic inhalation formulation.
Dry powder formulations face specific challenges, primarily maintaining API stability in dry powder during drying and ensuring effective aerosol dispersion from the inhaler.
- API Stability during Drying: Approaches such as water-replacement theory (using sugars like trehalose to mimic water’s hydrogen bonding) and glass stabilisation (using an amorphous excipient with a high glass transition temperature, or Tg) help preserve the API’s native structure.
- Aerosol Performance: Small particles are naturally cohesive. To ensure they redisperse effectively, excipients such as the amino acid leucine are commonly used. When located at the particle’s surface, leucine improves aerosol performance and enhances solid-state stability.
There is a limited selection of FDA-approved excipients for respiratory delivery. How can we address this gap for new, complex biologics?
Expanding the range of FDA-approved excipients for respiratory delivery is essential for advancing complex biologic development. The limited number of approved excipients remains a major challenge, particularly as molecular complexity increases.
To address this, the industry must explore novel excipients. This requires:
- Early Safety Assessment: Identify and begin evaluating new excipients early in development to achieve timely regulatory approval (FDA, EMA).
- Collaboration: Work closely with regulators and industry partners to avoid delays and build robust safety profiles for new materials.
- Focus on Function: Develop excipients specifically designed to improve drug delivery, absorption, and targeted action, supporting ongoing innovation in inhaled biotherapeutic development.
The value of excipient selection
This Q&A examines how excipients for respiratory delivery influence the stability, performance, and safety of biologic inhalation. It highlights how the right formulation choices can enhance manufacturing efficiency and support the successful development of new therapies. Considering biologic inhalation formulation early in the process can help reduce risk and improve long-term consistency. For further insight into formulation strategy or excipient selection, please contact our team to discuss how we can support your next project.
