A Brief History of Nasal Drug Delivery
Nasal drug delivery has significantly evolved since its inception several decades ago. Initially, it was primarily used for locally acting treatments related to decongestion and rhinitis, with some of the earliest multi-dose sprays appearing in the 1950s and 1960s. A major milestone was reached in 2003 with the approval of the first nasal vaccine, FluMist® Quadrivalent. Since then, pharmaceutical developers have pursued intranasal drug administration as a viable alternative to traditional routes. It has become an attractive option for various indications, including rescue therapies, infectious disease prevention, pain management, central nervous system conditions, and more.
Recent breakthroughs, such as Narcan® for opioid overdose reversal and the antidepressant Spravato® for treatment resistant depression, demonstrate a growing interest in novel nasal therapies. Additionally, the emergence of the COVID-19 pandemic in 2020 spurred vaccine development, renewing interest in intranasal and inhaled vaccine administration due to ease of administration and rapid action.
Advantages of Intranasal Drug Delivery
The nasal cavity is an ideal target for administering drugs locally and systemically, particularly to the central nervous system (CNS). The nasal mucosa is highly vascularised, providing a direct route for drug absorption into the bloodstream, which facilitates rapid onset of action. This efficient absorption can lead to reduced dosages compared to oral administration, as it bypasses first-pass metabolism in the liver. Moreover, intranasal administration is non-invasive and can usually be self-administered, enhancing patient compliance. These benefits underscore intranasal drug delivery as a valuable alternative for achieving rapid and effective therapeutic outcomes in various clinical settings.
Key Regulations and Consideration for Nasal Drug Development
The approval process for nasal drug products is governed by strict regulatory testing and development guidelines. Major regulatory bodies, such as the Federal Drug Administration (FDA) and the European Medical Association (EMEA), require comprehensive in vitro characterisation tests and in vivo clinical evaluations. While there are a variety of paths to approval depending on the drug product and region, there are several essential in vitro tests for nasal spray products that include Pump Delivery, Spray Pattern, Plume Geometry, Dose Content Uniformity, Aerodynamic Particle Distribution, and Droplet Size Distribution. These tests are essential for charactersing the emitted nasal spray and crucial for proper development and approval of nasal drugs products1.
When delivering drugs to the nasal cavity, it is critical to understand the relationship between the formulation, device, and the patient and to control their effects on both in vitro spray characteristics and potential implications for in vivo therapeutic outcomes. When developing a nasal drug product, it is essential to monitor the effects of these factors on spray characteristics to maintain equivalence to a reference product or internally defined product performance standards. These three factors dictate the location, amount, and therapeutic outcome of nasal drug products, making their development uniquely challenging.
