Development and Validation of Robust Analytical Method to Determine Droplets Size Distribution of Nasal Spray Using Laser Diffraction Technique

Abstract

In the recent past, delivery of therapeutic agents through the nasal route becoming a very attractive proposition, especially when rapid absorption and effects are required. The droplets size of a nasal spray dosage form is important for both efficacy and toxicity. In this study, an attempt was made to develop and validate a method to measure the droplets size distribution in Fluticasone nasal spray using Malvern spray tech coupled with automatic actuation station at various angles. Devices were actuated at the force of 6.0 kg, the velocity at 60 mm/s and rate of acceleration at 5000 mm/s2. Data was collected for 150 ms at a height of 6.0 cm from the tip of the device. The method was evaluated for their precision, robustness and impact of different actuation angle on the formation of droplets size. The study revealed that changing the actuation angle from 0° to 45° had no significant impact on droplets size distribution of brand-B, whereas, the Dv (90) of brand-A significantly affected. The repeatability of the method was assessed from the percent standard deviation of six replicate measurements and was found to be 3.2, 5.3, 9.1 and 11.1 for Dv (10), Dv (50), Dv (90) and less than 10 µm respectively. Similarly, the robustness of the method was evaluated by changing velocity and acceleration. When the velocity changed to 55 and 65 from 60 mm/s the percent difference in their Dv (10), Dv (50) and Dv (90) was found to be -4.2, -7.6 and -11.4 for 55 mm/s and 0.4, 0.2 and 0.5 for 65 mm/s. When the acceleration changed to 4500 and 5500 from 5000 mm/s2 the percent difference in their Dv (10), Dv (50) and Dv (90) was found to be -2.6, -1.7 and 0.1 for 4500 mm/s2 and -3.3, -1.7 and 0.5 for 5500 mm/s2. The results suggest that change in velocity and acceleration does not impact significantly on droplets size, thus ensures the robustness of the method. The method was applied to two commercially available nasal sprays labeled as Brand-A and Brand-B. The result has shown marginal differences in their Dv (10 and 50) but a significant difference observed in Dv (90) and Dv ˂10. The Dv (90) and Dv ˂10 of Brand-A and Brand-B was found to be 91.7; 0.8 and 66.9; 2.1µm respectively. The data presented here suggest that the developed method is precise and robust can distinguish the droplets size change in the products. Hence, this can be adopted in the pharmaceutical industries to check the characteristics of the spray products.