Unlike a tablet or injectable dosage form, the successful development of a nasal spray combination drug product is complex due to the interactions between the drug formulation, the nasal spray device, and how the end user will use the device. Proper planning and consideration into the design and development phase can help to navigate these considerations in developing a robust and reliable nasal drug product.
The design and development of drug products for intranasal delivery require many considerations to support the intended delivery and efficacy. Depending on the active pharmaceutical ingredient (API) target, the formulation will be assessed to determine the necessary deposition in the nasal cavity to achieve the desired goals for absorption. The target dose is typically determined via in-vivo efficacy/Pharmacokinetic (pK) profile/modelling, which provides a framework of excipients to incorporate into the formulation to support delivery to the intended target within the nasal cavity. For instance, nose-brain delivery require adhesion onto the nasal mucosa in addition to exceeding the quick cilia clearance. This requires the assessment of appearance, viscosity, pH and other physical properties for further formulation selection. The type of nasal spray device selected will depend on the type of indication, with unit & bi-dose devices used for acute indications versus multidose for chronic indications.
A key component of the formulation development and device selection is concurrent work on the spray characterization testing. As the formulation development is in process, and the device selection is moving towards finalization, the aspects of the formulation, device and patient all need to be coordinated to achieve a successful product. One driving force towards achieving this success is what Proveris Labs calls Ergo Testing. Ergo testing allow us to put the formulation/device combination(s) into a user’s hand and learn how they actuate the product. This provides the basis for understanding user actuation parameters that then can be utilized for the development of spray characterisation methods for the nasal drug product.
In the development process, small changes in the formulation that impact the physical characteristics of the formulation can change the spray performance from the nasal spray device. These differences in performance can be assessed by using in-vitro spray characterization testing. In addition, many nasal spray products need to target specific areas of the nasal cavity to achieve the desired efficacy of the drug product. Human factors, such as the insertion depth and insertion angel of the nasal spray device into the nostril can also affect the overall efficacy of the nasal spray performance. These risks can be mitigated by a thorough evaluation of the product using a nasal cast model, to quantitatively determine how the formulation, as well as human factors affect deposition in the different regions of the nasal cast.
To develop an effective, successful nasal spray product the full development process must include attention to detail in the formulation development, device selection, and human usage factors of the product. The performance at a specific nasal target can vary depending on the formulation excipients and concentrations, and the results from the deposition pattern in the nasal cast model can reveal if the deposition will achieve the required goals. If the target is off, reconfiguring the formulation and/or device in conjunction with suitable plume geometry and spray pattern characteristics would provide the tunability to meet the targeted deposition pattern requirements. Close attention to all critical details throughout the design, manufacturing, development and testing process are required to develop a successful nasal spray product. Please join us for this webinar to get an in-depth investigation of these variables that help to make Catalent and Proveris successful in their processes.
Key Learning Objectives
- Understanding the considerations necessary in formulation development
- What goes into nasal spray device selection
- Successful spray characterization methods development and testing
- Critical components of approved product batch release testing
