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Spray pattern and plume geometry tests are important indicators of aerosolization, spray performance and subsequent bioavailability of delivered drug. 20 OctOber 2017 Inhalation Spray pattern: A rapid and sensitive early development tool for respiratory drug products Utilizing spray performance measurements to accelerate OINDP development Lingzhi Liao, MS, Heli Chauhan, MS, Alyssa Newcomb, BS, Tim L'Ecuyer, BS, Shau Neen Liu-Cordero, PhD and Chip Leveille, BS Proveris Scientific Corporation e present study was designed to examine spray pat- tern against changes in the sump design for pressurized metered dose inhaler (pMDI) products, specifically orifice diameter, orifice length and sump chamber depth parameters (Figure 1). These parameters were found, in a previous study, to have the most significant effects on spray performance. 4 e results here corrobo- rate the previous study's findings and demonstrate how small variations in sump design, as well as variability introduced by other factors (canister, valve, formula- tion), drive significant changes in spray pattern area. Proveris Scientific's SprayVIEW ® measurement system can detect these small changes. This type of analysis gives valuable insight about various factors to control during the product development stage for both generic and new reference products. Materials and methods Materials All spray pattern measurements were performed on two reference pMDI products: ProAir ® HFA (Teva) and Ventolin ® HFA (GlaxoSmithKline). Two specific actu- ators (one for each product) were custom-designed to hold the canister and sump component fixture. Eight different sump components were developed to reflect the three-parameter, two-level design of experiment from Smyth, et al. as shown in Table 1. 4 e actuator's sump component was designed to be modular so all eight sumps could be replaced and tested. e actuator design maintained a horizontal spray but did not include a mouthpiece, in order to isolate the effects of the sump components. is design also removes a vari- able that can affect spray performance. Figure 1 high- lights each of the three parameters varied: orifice diam- eter, orifice length and chamber depth. e sump com- ponents were machined from black delrin with high precision tolerance (+ 5%), using CNC (computer numerical control) machining technique. Introduction Spray pattern and plume geometry have long been established as required tests for orally inhaled and nasal drug product (OINDP) characterization. Further- more, these tests are important indicators of aerosoliza- tion, spray performance and subsequent bioavailability (BA) of the delivered drug. 1 e industry guidelines for metered dose inhalers from the United States Food and Drug Administration (US FDA) state that, "Various factors can affect the spray pattern and plume geometry, including the size and shape of the actuator orifice, the design of the actuator, the size of the metering chamber, the size of the stem orifice of the valve, the vapor pres- sure in the container, and the nature of the formula- tion." 2 Understanding these effects becomes essential to successful drug development and approval. Establishing bioequivalence (BE) in generic drug devel- opment using these and other tests has proven to be chal- lenging. 3 Moreover, innovation companies can utilize spray pattern to design new products with performance parameters that are difficult to match. Often in generic product development, investigation into the spray per- formance begins too late in the process given the impor- tance of these measures. Understanding the relationship between the device and formulation and their effect on spray performance is a critical step in obtaining repro- ducible performance or achieving bioequivalence. Fail- ure to gain this understanding can result in a costly rede- sign and a delay in product approval. Spray pattern is a highly sensitive and rapid measure- ment technique, which makes it an ideal tool early in product development. This sensitivity provides an opportunity to fully understand the interactions between a large number of factors related to device design, formulation and patient usage. Obtaining this product information is essential in achieving proper drug delivery and performing successful BA/BE studies.