Barriers to pulmonary drug delivery
Inhaled administration is a complex process and is highly dependent on the respiratory system physiology, delivery device, characteristics of the formulation and exploitation of excipients. There are considerable barriers when delivering drugs to the lung that need to be overcome for effective and efficacious therapies:
- There are mechanical barriers including drug particle impaction in mouth, nose and large airways
- Mucociliary clearance
- Chemical and immunological barriers such as actions of enzymes that hydrolyse and deactivate proteins and peptides as well as surfactants in the lung that prevent adhesion
- Disease state-associated factors.
Alongside the more physiological barriers there are chemical and formulation challenges that can hinder the efficacy of inhaled formulations:
- Chemical instability of the active ingredients
- Aggregation of biologics post-spray
- Particle size control and deposition
- Batch-to-batch reproducibility.
Reducing impurity profile for pulmonary drug delivery
Excipients are generally used to improve the chemical and physical stability of the active pharmaceutical ingredient (API), modify release profile to enhance its absorption or deposition in the target lung regions, enhance the formulation flowability, and increase dosing reproducibility. However, excipients can contain impurities that can impact the efficacy and performance of an inhaled formulation. These impurities such as metal ions, free fatty acids, peroxides and aldehydes can arise from raw material sourcing, processes during manufacture and degradation of the excipient.
Using high purity excipients that have a reduced impurity profile can maximise the success rate of drug development by offering enhanced API stability, reduced cellular irritation and dosing reproducibility in the final formulation. Croda’s Super Refined™ process yields highly purified excipients that can help overcome both physiological and formulation challenges encountered in pulmonary delivery for a range of modalities including small molecules, antibody therapeutics, peptides and proteins, cell and gene- based therapeutics as well as nucleotide-based therapeutics.