Evaluation of a Device Modification and Hand-Related Variability on the Performance of Nasal Sprays and Metered Dose Inhalers

Abstract

Drug delivery to the nose and lungs using nasal sprays and metered dose inhalers (MDIs) is complicated by a reliance on the formulation, device, and patient to generate droplets or particles within a suitable particle size range so that drug deposits at an appropriate location. Many properties of the formulation, device, and patient have been investigated for their role in nasal spray and MDI performance. However, no published works have studied the influence of the dip tube during emptying of the nasal spray, or how patient-relevant hand technique affects nasal sprays or MDIs. Therefore, the purpose of this work is to investigate the effects of a flexible dip tube modification on emptying characteristics of nasal sprays, and to evaluate the influence of hand technique on nasal sprays and MDIs. The number of full sprays and the number of sprays in the tail-off period generated at thirty degrees to the vertical by flexible and rigid dip tubes were determined in five over-the-counter nasal sprays. Results showed that flexible dip tubes were able to generate significantly more sprays before the tail-off period in four of the five nasal sprays tested. Three of the five nasal sprays showed significantly fewer sprays in the tail-off period when flexible dip tubes were used in place of their rigid counterparts. Hand data recorded from adults and children were used to conduct in vitro tests on nasal sprays using force-controlled and velocity-controlled actuators. Variability in hand spraying led to significant differences in patient-relevant actuator settings between the adult and pediatric groups. Also, a significantly decreased spray weight was recorded in children compared to adults. While variability among participants was high, only actuation force, force rise time, and compression velocity resulted in significantly different in vitro test results. Although hand variability was high when adults sprayed two MDIs, the variability in the recorded spray weight was low. This suggests that hand technique does not play a dominant role in the resultant dose and/or spray characteristics, as long as the participant is able to apply enough force to the MDI to compress the valve spring and release the product.