A study of Formulation and Delivery Device-Related Effects on In Vitro Performance of Nasal Sprays
Jernej Grmas1, Badre Hammond2, Rade Injac1, Rok Dreu3, Gerallt Williams2
1 Lek Pharmaceuticals d.d., Ljubljana, Slovenia
2 Aptar Pharma, Le Vaudreuil, 27100, France
3 Faculty of Pharmacy, University of Ljubljana , Ljubljana, Slovenia
The aim of this work is twofold: firstly, to use systematic DoE (design of experiments) approach to study both formulation and delivery device properties to establish design and control space to assure desired performance, and secondly, to show that product performance is stable and robust within expected range of operation and handling. This study combines three factors, viscosity of suspension, nozzle orifice diameter (OD), and shot weight, at three levels using the DoE approach of D-optimal design model. Nasal spray performance responses from this study were DSD (droplet size distribution) and SP (spray pattern) in vitro tests. In addition, the amount of work needed for specific actuation was integrated from force–displacement profiles and used as response in DoE.
Viscosity has a dominant effect on DSD and modest effect on SP, with lower viscosities related to generation of smaller DSD and larger SP. Orifice diameter was found to have the highest impact on SP, with larger diameter resulting in larger SP. Shot weight factor exerts significant influence on all tested metrics. Work, however, did not vary greatly with suspension viscosity or orifice diameter. Shot weight is the most dominant factor for work and important for DSD having a positive effect on both responses. By appropriate adjustments and control of formulation or device factors, desired performance can be assured.
Robust and reproducible in-vitro performance is assured by device design, where certain force threshold needs to be achieved in order to start with actual spray formation.