Patent Publication Number: US-2010116070-A1

Title: Method and Apparatus for Measuring Manual Device Actuation

Description:
RELATED APPLICATION(S) 
     This application is a continuation of U.S. application Ser. No. 10/825,082, filed Apr. 14, 2004, which claims the benefit of U.S. Provisional Application No. 60/462,861, filed on Apr. 14, 2003. The entire teachings of the above applications are incorporated herein by reference. 
    
    
     BACKGROUND OF THE INVENTION 
     A spray pump&#39;s performance is characterized in terms of its emitted spray pattern, plume geometry, and/or droplet size distribution. These parameters are known to be affected by the means in which the spray pump is actuated. For example, slow actuation will likely cause poor atomization, producing a stream-like flow. Fast actuation will likely produce too fine a spray, leading to poor absorption in the nasal mucosa and unwanted inhalation and deposition of the droplets in the throat and lungs. These factors and others, such as drug compatibility with the spray device, may result in the drug delivery falling outside the criteria associated with an original clinical trial approval. Testing the delivery or spray devices may be done to verify the spray device actuates the drug within the criteria of the original clinical trial approval, but operator actuation variability may adversely affect test results. 
     SUMMARY OF THE INVENTION 
     Automated actuation of nasal spray devices subject to in vitro bioequivalence testing may be employed to decrease variability in drug delivery due to operator factors (including removal of potential analyst bias in actuation) and increase the sensitivity for detecting potential differences among drug products. An automated actuation system may include settings for force, velocity, acceleration, length of stroke, and other relevant parameters. Selection of appropriate settings is relevant to proper usage of the product by a trained patient, and, for nasal sprays, may be available from pump suppliers for tests such as droplet size distribution by laser diffraction or spray pattern photographic techniques. In the absence of recommendations from the pump supplier, settings may be documented based on exploratory studies in which the relevant parameters are varied to simulate in vitro performance upon hand actuation. Exploratory studies of hand actuation of the spray pump device are useful to determine appropriate settings for automated actuation. 
     Accordingly, one embodiment of the principles of the present invention includes an assembly that provides information about operation of a spray device. The assembly includes an adapter assembly configured to be coupled to a movable part of the spray device. In the ease of a nasal spray, the movable part is the nasal tip and, in the case of a Metered Dose Inhaler (MDI), the movable part is the canister containing the drug. The assembly also includes a mounting assembly configured to be coupled to a stationary part of the spray device. In the case of the nasal spray device, the stationary part is the bottle containing the drug and, in the ease of the MDI, the stationary part is the mouthpiece. The assembly also includes a transducer, coupled to the mounting assembly or the adapter assembly. The assembly also includes a linkage that is adapted to extend between the mounting assembly and the adapter assembly. The linkage is in operational relationship with the transducer to enable the transducer to indicate a mechanical relationship between the movable and stationary parts of the spray device corresponding to the operation of the spray device. 
     The mounting assembly may include a bearing and shaft assembly coupling the adapter assembly to the mounting assembly. The bearing and shaft assembly may substantially maintain alignment between the adapter assembly and the mounting assembly in non-actuation axes. 
     The assembly may also include a base assembly adapted to be coupled to the mounting assembly. The base assembly may include a foot assembly with a footprint that supports the spray device in a vertical relationship with the foot assembly. The assembly and spray device may have a predetermined weight for use on a weight measuring scale sensitive enough to measure a change in fluid ejected by the spray device in a single discharge. In one embodiment, the total weight of the assembly and spray device is less than or equal to 200 grams. 
     The transducer may be a position sensor. An example of one such position sensor is a potentiometer. In the case of the potentiometer, the linkage is a spring loaded wire integrally associated with the potentiometer. 
     The adapter assembly may be configured to interface with an automated actuation system that operates the spray device in an automated manner. The transducer may indicate the mechanical relationship in a format usable by the automated actuation system. 
     The assembly may also include a data processing system coupled to the transducer that captures indications of the mechanical relationship between the movable part and the stationary part of the spray device. The data processing system may include program instructions that automatically calculate parameters in position, velocity, or acceleration corresponding to operation of the spray device. The instructions may include a routine that calculates velocity or acceleration data from position measurements using a least squares technique. The parameters may include at least one of the following: maximum position displacement, hold time, maximum actuation velocity, maximum return velocity, maximum actuation acceleration, and maximum return acceleration. The actuation direction is defined herein as the direction in which the movable part causes atomization of the liquid drug contained in the spray device, and the return direction is defined herein as the direction in which the movable part returns to its state of rest. The data processing system may also include a signal conditioner, data sampler, and amplifier, wherein the signal conditioner conditions a signal effected by the transducer prior to the data sampler and amplifier operating on the signal. 
     The principles of the present invention include corresponding methods related to the above-described apparatus and alternative embodiments thereof described below. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The foregoing and other objects, features and advantages of the invention will be apparent from the following more particular description of preferred embodiments of the invention, as illustrated in the accompanying drawings in which like reference characters refer to the same parts throughout the different views. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention. 
         FIG. 1  is an illustration of an example application in which the principles of the present invention may be employed; 
         FIGS. 2A-2B  are diagrams of spray devices ejecting an atomized drug produced by actuation of the spray device containing the drug used in the application of  FIG. 1 ; 
         FIG. 3  is a diagram of an assembly connected to the spray device of  FIG. 1 ; 
         FIG. 4  is an alternative embodiment of the assembly of  FIG. 3 ; 
         FIGS. 5A-5B  are side views of the assembly embodiments of  FIGS. 3 and 4 , respectively; 
         FIG. 6  is an embodiment of the assembly of  FIG. 3  in which a shaft and bearing assembly is employed; 
         FIG. 7  is a side view of the assembly of  FIG. 6 ; 
         FIG. 8  is a diagram of an automated actuation system used in the application of  FIG. 1 ; 
         FIG. 9  is a block diagram of a data capture and processing system adapted to be used with the assembly of  FIGS. 3 and 4 ; 
         FIG. 10  is an alternative embodiment of the data capture and processing system of  FIG. 9 ; 
         FIG. 11  is a process optionally used with the data capture and processing systems of  FIGS. 9 and 10 ; 
         FIG. 12  is a user interface optionally used with the data capture and processing systems of  FIGS. 9 and 10 ; 
         FIG. 13  is a set of waveform diagrams illustrating captured data associated with the spray devices of  FIGS. 2A-2B ; and 
         FIGS. 14-17  are actual test data associated with in vitro testing and automated testing of the spray device of  FIG. 2A . 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     A description of preferred embodiments of the invention follows. 
       FIG. 1  illustrates a spray device application in which the principles of the present invention may be employed. A person  105  uses a spray device  100 , such as a nasal spray pump or Metered-Dose Inhaler (MDI), to receive a drug supplied in a liquid form. In the case of a nasal spray pump, the person  105  uses his hand  115  to actuate the spray device  100  to cause the liquid drug to be atomized and projected into a nostril  110 . In the case of an MDI, the person  105  uses hand actuation to project an atomized drug into his mouth  120 . 
     It has been observed that different age groups apply different forces to the spray devices  100 . Therefore, a drug development company and/or spray device manufacturer cannot always predict the amount of drug that will reach the intended nasal rnucosa. A regulatory body, such as the Food and Drug Administration (FDA), may approve a given drug for a predetermined dose. However, spray device manufacturers rarely, if ever, know what the appropriate settings should be for automated actuation testing. This is primarily due to the fact that the device manufacturers rarely have the requisite knowledge of the physical properties of the drug formulation (e.g., viscosity and surface tension) because the formulations are proprietary to the drug company. Thus, the spray device manufacturers generally do not know how these properties will affect the characteristics of the spray the spray device produces when actuated by hand or by an automated actuation system. Additionally, the spray device manufacturer may not have the same automated actuation system as the drug company, thereby further reducing their ability to supply the appropriate actuation settings to the automated actuation system. Moreover, in practice, based on a person&#39;s age group, the amount of drug ejected (i.e., dosage) from the spray device  100  may be different from expected. Therefore, the amount absorbed by the person  105  may be different from what the regulatory body approved in clinical trials, thereby causing concern that a person&#39;s response to the drug may be different from the criteria determined to be safe and effective in the clinical trials. Some other factors that affect the amount of drug discharged by the spray device  100  are atomization rate of the drug, droplet size, spray pattern, plume geometry, priming and re-priming rates, and environmental conditions. 
       FIGS. 2A and 2B  illustrate spray patterns  200   a  and  200   b , respectively, produced by the same or different spray devices  100 . In  FIG. 2A , the spray pattern  200   a  is projected in a relatively conical pattern. In  FIG. 2B , the drug is more atomized than in  FIG. 2A  as evidenced by a broader spray pattern  200   b.    
     Spray pattern studies characterize a spray either during the spray prior to impaction or following impaction on an appropriate target, such as a thin-layer chromatography (TLC) plate. Spray patterns for certain nasal spray products may be spoked or otherwise irregular in shape. 
     Spray patterns can be characterized and quantified by either manual or automated image analysis. Both analyses allow shape and size to be determined. Automated analysis systems may also allow determination of Center of Mass (COM) and/or Center of Gravity (COG) within the pattern to be determined. 
     Plume geometry describes a side view of the aerosol cloud parallel to the axis of the plume. High-speed photography, laser light sheet, and high speed digital camera or other suitable methods are generally used to determine plume geometry. 
     Priming and re-priming data also ensure delivery of a dosage of drug and are taken into account when measuring spray patterns  200   a  and  200   b  to accurately model in vitro operation. 
       FIG. 3  is an illustration of an example assembly that may be adapted to interface with the spray device  100 . In accordance with the principles of the present invention, the assembly is adapted to indicate a mechanical relationship between a movable part  305  and a stationary part of the spray device  100  corresponding to operation of the spray device  100 . In a nasal spray pump application, the movable part  305  may be referred to as a nasal tip since it is inserted into the nostril  110 . The stationary part  310  may be referred to as a nasal spray pump bottle in this application. 
     Components that are connected to the spray device  100  include (a) an adapter assembly  315   a , which connects to the movable part  305 , (b) a mounting assembly  320   a , which connects to the spray device  100 , (c) a transducer  335 , which is connected to the mounting assembly  320   a  in this embodiment but may be connected to the adapter assembly  315   a  in other embodiments, and (d) a linkage  330 , which may be a spring loaded draw wire that is adapted to extend between the mounting assembly  320   a  and adapter assembly  315   a . The linkage  330  is in operational relationship with the transducer  335  to enable the transducer  335  to indicate the mechanical relationship between the movable part  305  and the stationary part  310  of the spray device  100  corresponding to operation of the spray device  100 . 
     The transducer  335  may be a position sensor, such as a potentiometer. Extending from the potentiometer is a transducer cable  340  providing a transducer output. The transducer cable  340  connects at the other end (not shown) to a data acquisition (DAQ) circuit board (not shown) or other electronics to capture and/or process the transducer output. 
     The mounting assembly  320   a  may be connected to the stationary part  310  through use of flexible tie straps  325 . Other connection means may also be used, such as Velcro® straps, adhesive, or other suitable attachment means. A rubber or other suitable material may be used to form a solid connection between the adapter assembly  315   a  and the movable part  305 . Securing of the adapter assembly  315   a  or the mounting assembly  320   a  to the respective parts  305 ,  310  of the spray device  100  may be completed through screw means, latching mechanism, or other suitable mechanism. 
     In this particular embodiment, the draw wire  330  is kept taut enough by the spring in the transducer  335  to prevent sluggishness without deflecting the movable part  305  of the spray device  100  or the adapter assembly  315   a . The lateral location of the transducer  335  relative to the mounting assembly  320   a  is then adjusted and tightened against the mounting assembly  320   a  so that the draw wire  330  is parallel to the actuation axis of the spray device  100 . 
     In operation, a person  105  operates the spray device  100  in a typical manner by placing his fingers on the adapter assembly  315   a  and drawing it toward the mounting assembly  320   a  to cause the movable part  305  to move. The motion produces a “shot” or dosage to the expelled from the spray device  100 . When the spray device  100  is actuated, the linkage  330  causes the transducer  335  to change its state. A change in state of the transducer  335  causes the transducer output to change state in a proportional manner. The data acquisition circuit board (not shown) captures the change in state of the transducer  335  and provides the captured data to a processor for further processing. Prior to testing, the transducer  335  may be calibrated and used during the processing. 
       FIG. 4  is an illustration of the components applied to a metered-dose inhaler (MDT)  400 . The spray bottle  100  and MDI  400  are interchangeably referred to herein as “spray devices”. In the case of the MDI  400 , a pressurized canister  405  is the movable part, and a mouthpiece  410  is the stationary part. A person&#39;s hand  115  squeezes the pressurized canister  405  toward the mouthpiece  410  to actuate the MDI  400  and cause a “shot” to be expelled from the MDI  400 . 
     Similar to its usage with the spray bottle  100 , the linkage  330  extends between the adapter assembly  315   b  and mounting assembly  320   b . The linkage  330  causes the transducer  335  to change states, which is transmitted by way of the transducer cable  340  to a data acquisition system or other processor (not shown). 
       FIGS. 5A and 5B  include indications of axes associated with the spray devices  100  and  400 . Referring to  FIG. 5A , an actuation axis  505   a  extends from the movable part  305 , and a draw wire axis  510   a  extends along the linkage  330 . Also indicated in  FIG. 5A  is a pair of adjustment slots  520  and corresponding adjustment screws  515  that hold the transducer  335  (hidden by the mounting assembly  320   a ). 
     In  FIG. 5B , the actuation axis  505   b  extends vertically from the pressurized canister  405 , and the draw wire axis  510   b  extends along the linkage  330 . 
     In both cases of spray devices  100 ,  400 , rotation of the linkage  330  about the actuation axis  505   a ,  505   b  causes the transducer  335  to change state much faster than normal operation of the spray device  100  (i.e., actuation along the actuation axis  505   a ,  505   b ). Such a rotation of the linkage  330  is possible if the adapter assembly  315   a ,  315   b  slips (i.e., spins about the actuation axis). Similarly, pivoting of the adapter assemblies  315   a  and  315   b  causes the linkage  330  to rapidly affect the state of the transducer  335 . Rapid changes in the output of the transducer  335  affects in vitro measurements. Therefore, the assembly described may be improved by having a more rigid connection between the mounting assembly  320   a  and the adapter assembly  315   a . An assembly providing a more rigid connection and, therefore, less measurement error, is illustrated in  FIG. 6 . 
       FIG. 6  illustrates an embodiment of an assembly  600  that employs a bearing  610  and shaft  605  assembly that substantially maintains alignment between the adapter assembly  315   c  and the mounting assembly  320   c . The linkage  330  is extended through the shaft  605  and connects to a shaft head  615  by extending through a center hole in the shaft head  615 . The linkage  330  may be held in place through use of a slot  630  designed for this purpose. 
     By using the bearing  610  and shaft  605  assembly, the pivoting of the movable part  305  of the spray device  100  is dramatically reduced over the embodiment of  FIG. 3 . Further, the assembly  600  may be constructed of lightweight materials, such as aluminum, to allow a person  105  to operate the spray device  100  in an unimpeded manner to simulate typical use of the spray bottle  100 . The shaft  605  may be a hardened precision shaft constructed of ¼″ O.D. stainless steel. The bearing  610  may be lined with various materials to allow the shaft  605  to travel smoothly and freely, thereby facilitating unimpeded in vitro motion. 
     In this embodiment, the mounting assembly  320   c  is connected to a foot assembly  620  via a bracket assembly  625 . Screws or other connection means are used to connect the bracket assembly  625  to the mounting assembly  320   c  and the foot assembly  620 . The foot assembly  620  is adapted to allow the entire assembly  600  to stand in a vertical arrangement such that the spray device  100  is held in a vertical relationship with the foot assembly  620  and suspended above a surface (e.g., weight measuring scale platform or table top) on which the foot assembly  620  rests. 
     The assembly  600  and spray device  100  may have a predetermined weight for use on a weight measuring scale that is sensitive enough to measure a change in fluid ejected by the spray device in a single discharge. Accordingly, if the foot assembly  620  is frame-like, weight can be minimized to meet a lightweight criterion. For example, the total weight of the assembly  600  and spray device  100  may be required to be less than 200 grams. If even more weight need be removed from the assembly  600 , the bracket assembly  625  can also be formed in a frame-like manner, as shown. 
       FIG. 7  is a side view of the assembly  600  with the spray device  100 . The mounting assembly  320   e  includes adjustment screws  515  and slots  520  to accommodate spray devices  100  having different diameters. Similar adjustment means may be provided on the adapter assembly  315   c . Various types of alignment means may be provided to remove motion in a cross-axis to the actuation axis  505   a  ( FIG. 5A ). 
     The MDI  400  generally maintains alignment in the actuation axis  505   b . Therefore, the shaft  605  and bearing  610  design is generally unnecessary for allowing the transducer  335  to indicate the mechanical relationship between the movable part  405  and the stationary part  410  of the MDI  400  without having errors caused by rapid changes in length of the linkage  330 . 
       FIG. 8  is an illustration of an automated actuation system  800  that operates the spray device  100  in an automated manner. The automated actuation system  800  includes a compression plate assembly  805  that travels vertically along a pair of passive, parallel, guide bars  810 . In one embodiment, a drive motor assembly (not shown) drives a belt and pulley assembly (not shown) that drives a drive plate assembly  835  along a drive rod  830 . The drive plate assembly  835  is connected to the compression plate assembly  805  in this embodiment. In response to upward force by the drive plate assembly  835 , the compression plate assembly  805  presses upward on the stationary part  310  of the spray device  100  to actuate the spray device  100 . Alternatively, a clamp (not shown) or other attachment means may be used to attach the stationary part  310  of the spray device  100  to the compression plate assembly  805 . Embodiments of automated actuation systems  800  are further described in co-pending U.S. patent application Ser. No. 10/176,930 (Attorney Docket No. 3558.1005-001) entitled, “Precise Position Controlled Actuating Method and System”, filed on Jun. 21, 2002; the entire teachings of which are incorporated herein by reference in their entirety. 
     To facilitate engagement of the assembly  600  with the automated actuation system  800 , the adapter assembly  315   c  may be configured to fit into a predefined cut-out  823  in the top 825 of the automated actuation system  800 . Also, in this embodiment, the bracket assembly  625  is disconnected from the foot assembly  620  to allow for the proper interfacing of the assembly  600  with the automated actuation system  800 . 
     The motor assembly and a portion of the belt and pulley assembly may be deployed in a housing  820  of the automated actuation system  800 . At least one processor (not shown) and voltage or current drive amplifier(s) (not shown) may also be deployed in the housing  820 . The drive amplifier(s) may be used to control drive motor(s) in the drive motor assembly. 
     In one embodiment of the automated actuation system  800 , the compression plate assembly  805  includes a force transducer (not shown), such as a piezoelectric transducer, that is positioned to sense actuation force of the spray device  100  caused by upward force applied by the compression plate assembly  805 . The force transducer may convert force to an output signal (e.g., voltage, current, or charge) in a proportional manner and transmit the output signal on a cable  815  to a sense amplifier (not shown). The sense amplifier is adapted to receive the output signal and convert it to a signal, with minimal additional noise, that can be sampled and processed by the processor. 
     Alternative embodiments of the automated actuation system  800  may also be employed. For example, the compression plate assembly  805  may include the drive motor assembly, which may employ linear voice coil motor(s), and the drive amplifier(s) may be in the housing  820 . In such an embodiment, the cable  815  carries electrical power signals between the drive amplifier(s) and motor(s) (not shown) in the compression plate assembly  805 . The cable  815  may also include feedback wires to allow for closed-loop control. Alternatively, the compression plate assembly  805  may include all the processing and drive amplifiers necessary for driving the spray device  100 , in which case, the cable  815  carries power and trajectory signals to the motor(s) and processor(s). Other combinations of electronics locations and wiring are also possible. 
     Forms of control that the automated actuation system  800  may use to operate the spray device  100  are open-loop control, closed-loop control, or combination thereof. A Proportional, Integration and Differentiation (PID) controller (not shown) may be employed to provide smooth operation of the compression plate assembly  805 . Alternatively, a digital controller may be employed. The output from the transducer  335  may be used for closed-loop control of the spray device  100  since the transducer  335  directly measures the effect of the compression plate assembly  805  actuating the spray device  100 . Use of open- or closed-loop control may be based on at least one parameter, such as an error budget associated with force, acceleration, velocity, position, length of stroke, or other relevant parameters. 
     A trajectory input (i.e., an actuation profile) to the compression plate assembly  805  is preferably as close to in vitro actuation of the spray device  100  as possible to test the performance of the spray device  100 . In this way, the automated actuation system  800  can actuate the spray device  100  in a manner that allows for near in vitro test conditions. Such testing allows a drug development company or spray device manufacturer to test the performance of the spray device  100 . The automated actuation system  800  may be used in conjunction with an automated spray characterization (i.e., spray pattern measurement) system that measures spray pattern, plume geometry, priming and repriming metrics, and/or other metrics associated with actuation of the spray device  100 . 
       FIGS. 9-17  illustrate a processing system and signals captured or generated thereby. The data processing system  900  captures data produced by the transducer  335 . The data processing system  900  is typically distinct from control electronics associated with the automated actuation system  800 , but data captured, processed, and/or produced by the data processing system  900  may be transferred to the automated actuation system  800  for use in automated actuation of the spray device  100 . Data may be transferred between the data processing system  900  and the automated actuation system  800  via a local area network (LAN), magnetic disk, optical disk, infrared signals, a Wide Area Network (WAN) such as the Internet, or other signal or data transfer means. 
     Referring first to  FIG. 9 , the data processing system  900  includes the transducer  335 , which receives stimuli via the linkage  330  as a function of the mechanical relationship between the movable part  305  and the stationary part  310 . In turn, the transducer  335  indicates the mechanical relationship. 
     A signal conditioner  905  is connected to the transducer  335  and provides an output signal to an amplifier  910 . The amplifier is connected to and provides an output to a data sampler  915 . The data sampler  915  is connected to a processor  920 . The processor  920  may output information related to the indication of the mechanical relationship between the movable and stationary parts of the spray device  100  on a display  925  and/or transfer data or parameters associated with the data to the automated actuation system  800 . 
     In operation, the signal conditioner  905  provides low-level signal conditioning of signals affected by a change of state of the transducer  335 . The signal conditioner  905  may have predetermined knowledge of the type of transducer  335  with which it is in communication. For example, the signal conditioner  905  may provide a consistent current to the transducer  335  if the transducer  335  is a potentiometer. In this example, the signal conditioner  905  may have internal circuitry (not shown) that measures voltage across the potentiometer to provide a measurement as a function of a change of state of the potentiometer caused by a change in length of the linkage  330  resulting from motion of the movable part  305  with respect to the stationary part  310 . 
     The signal conditioner  905  outputs a smooth representation of the voltage to the amplifier  910  corresponding to the indication of the mechanical relationship between the movable and stationary parts of the spray device  100 . A waveform  902  represents an example signal indicating motion of the movable part as indicated by the transducer  335 . An output from the signal conditioner  905  is shown as a signal  907  that the amplifier  910  amplifies for capture by a data sampler  915 . The data sampler, in turn, produces a digitized waveform  917 , which is received by the processor  920 . The processor  920  may process the digitized signal  917  for determining, for example, parameters associated with in vitro operation of the spray device  100 . 
       FIG. 10  is an alternative embodiment of the data processing system  9005 . The transducer  335  receives an input of +5VDC  1005  and an output of 0-5VDC  1010 . A data acquisition (DAQ) circuit board  1015  captures the output generated by the transducer  335 , which in this case is a position transducer. Therefore, the output from the transducer  335  directly relates to the position of the movable part  305  with respect to the stationary part  310 . The DAQ board  1015  may be in communication with a general purpose computer in a daughterboard arrangement. The information captured by the DAQ board  1015  may be displayed on a monitor  1020  and controlled via a Graphical User Interface (GUI) by either a keyboard  1025  or mouse  1030 . In this way, a user may provide various parameters and other forms of control to cause the DAQ board  1015  to collect the output  1010  from the transducer  335  in a customized manner. 
       FIG. 11  is a flow diagram of a process that may be employed by the data processing systems  900   a ,  900   b . The process  1100  may start by initializing the software variables in the DAQ board  1015  (step  1105 ). The process  1100  continues and checks for a status change in user input parameters (step  1110 ). Examples of user input parameters are sampling frequency, scale factors, and voltage output levels from the DAQ board  1015  to the transducer  335  (i.e., the input  1005  to the transducer  335 ). If the input value has not changed (step  1115 ), the process  1100  checks again for a status change in user input parameters (step  1110 ). If the input value has changed (step  1115 ), the process  1100  continues to operate as specified by the user. 
     The process  1100  may acquire sensor response data and compute actuation parameters (step  1120 ). The process  1100  may also save a report of response histories, acquisition parameters, and sensor information (step  1125 ). Saving the information may include saving information to a server, local memory, or portable computer readable medium. The process  1100  may also reset all parameters to initial conditions (step  1130 ). The process  1100  may also quit the program (step  1135 ) in response to user input. Other processes may also be executed by the process  1100  that are different from the examples listed. 
       FIG. 12  is an example Graphical User Interface (GUI)  1200  in which a user may program input conditions, acquisition parameters, and view captured waveforms and associated parameters. A set of input fields  1205  includes information related to materials being tested, and personnel involved in the testing, such as manufacturer, drug name, lot/device ID, experiment type (e.g., hand or automated actuation), starting dose number, operator, and report path to which the captured data is stored. A second set of inputs  1210  relates to the transducer  335 , including serial number and a calibration table, where the calibration table allows for input such as gain, de offset, scale factor, or other parameters related to the calibration of the transducer  335 . Another set of parameters input by the use of the GUI  1200  is a set of acquisition parameters, such as data acquisition collection time span (e.g., one second) and sampling frequency (e.g., 1 kHz). 
     The GUI  1200  also include a graphics area displays a position plot  1220  of the position versus time of the movable part  305  with respect to the stationary part  310 . The GUI  1200  displays multiple parameters  1225  associated with the position plot  1220 . The parameters  1225  in this embodiment include a hold time of 98 msec, stroke length of 0.50 mm, actuation stroke velocity of 38.49 mm/s, acceleration of 2961.13 mm/s 2 , return stroke velocity of −35.45 mm/s, and return stroke acceleration of −1772.30 mm/s 2 . In one embodiment, the measured parameters  1225  are automatically calculated based on the data captured and displayed in the position plot  1220 . 
       FIG. 13  provides graphical representations of position, velocity, and acceleration. The representations are representative of motion of the movable part  305  with respect to the stationary part  310  in a typical spray device  100 ,  400  by in vitro actuation or automated actuation. A position curve  1305  is similar to the position curve in the position plot  1220  of  FIG. 12 . The position curve  1305  rises during an actuation time, remains at a position (P ACT ) during a hold time  1325 , and decreases from P ACT  during a return time  1330 . A corresponding velocity curve  1310  rises to a maximum velocity V ACT  halfway during the actuation time and decreases back to a zero velocity during the hold time  1325 . The velocity decreases to a maximum negative velocity (V RTN ) and returns to zero during the return time  1330 . 
     An acceleration curve  1315  illustrates the corresponding acceleration curve  1315  to the position curve  1305  and velocity curve  1310 . During the actuation time  1320 , the acceleration increases and decreases to maximum accelerations (A ACT ). Similarly, during the (+/−A ACT ) return time  1330 , the acceleration decreases and increases to maximum accelerations (+/−A RTN ). The maximum accelerations may be calculated as an average of the magnitude of +/−A ACT  levels, and the maximum return accelerations may be calculated as an average of the magnitude of +/−A RTN  levels. 
     Processing to calculate the velocity and acceleration curves from captured position data may be performed in an automated manner. For example, a software routine that calculates velocity or acceleration data from position measurements may use a least squares technique. An example of such a routine may use a Savitzky-Golay smoothing and differentiation filter that optimally fits a set of data points to polynomials of different degrees. This type of filter is useful for substantially reducing noise in a manner better than a point-to-point differentiation technique does. Other smoothing filters and processes may also or alternatively be employed. 
     It should be understood that if the transducer  335  is an acceleration or velocity transducer, integration and/or differentiation techniques may be used to provide the other motion data, plots, and parameters. 
       FIGS. 14-17  are plots that were produced by a method to measure hand actuation parameters for nasal spray pumps that can be used for automated actuation. Actuation parameters were measured for representative commercially available spray pumps filled with water. The average actuation parameters were then checked to confirm that the automation actuation system  800  accurately duplicated the ergonomics of hand actuation. The actuation parameters were optimized within a working range of the hand actuation parameters to obtain shot weight delivery closest to the delivery target (e.g., label claim by the pump manufacturer). 
     Methods for producing the plots of  FIGS. 14-17  include a hand actuation portion, a congruency test portion, and an optimized automated actuation portion. 
     Referring first to the hand actuation test portion of the method, three patients were trained on the method for hand actuation. Three primed nasal spray pumps were actuated by hand ten times each by the three patients. The actuation parameters were measured using a data processing system, such as the systems  900   a  and  900   b  of  FIGS. 9 and 10 , respectively, and the assembly  600  of  FIG. 6 . After each actuation, expelled shot weight (i.e., liquid expelled during actuation) was measured and is shown in  FIG. 14 . A curve for each of the three bottles was recorded and displayed in the plot  1400  in  FIG. 14 . 
     The shot weight performance by hand actuation of the three nasal spray pumps is shown. The shot weight average was 92.6 mg compared to a design delivery target of 100.2 mg. The standard deviation associated with shot weight was 9.2 mg across all actuations. Bottle  1  (curve  1405 ) had the highest standard deviation of 10.6 mg across all actuations. 
     In the congruency test portion of the method, the average actuation parameters from hand actuation were programmed into the automated actuation system  800  of  FIG. 8 . Three primed spray devices  100  were actuated ten times. A quantitative comparison of the position versus time curves measured by each method is shown in  FIG. 15 , where the hand measurements are shown in the heavy-lined curve  1505  and the automated measurements are shown in the light-lined curve  1510  in the plot  1500 . Shot weight delivery performance for the three units obtained by automated actuation is shown in  FIG. 16 , with each of the curves  1605 ,  1610 , and  1615  corresponding to spray bottles  1 ,  2 , and  3 , respectively, in the plot  1600 . 
     The shot weight performance by automated actuation of three bottles using average actuation parameters (not optimized) is shown. The shot weight average was 76.0 mg. The standard deviation associated with shot weight decreased from 9.2 mg with hand actuation to 5.9 mg across all actuations, using automated actuation, a 35.9% reduction. Bottle  1  (represented by curve  1605 ) had the highest standard deviation of 4.12 mg across all actuations. 
     In the optimized automated actuation portion of the method, three primed units were each actuated ten times in a series of tests that independently varied stroke length, hold time, and Intra Actuation Delay (IAD) within the working ranges previously measured during the hand actuation portion of the method. The stroke length was varied from the average value minus one standard deviation (“−1σ”) to the maximum stroke length that did not damage the bottle. The hold time was varied from the average value −1σ to the point where the shot weight did not increase more than 10% from previous actuations. The IAD was varied from 30, 15, 5, to 1 second(s). The data were analyzed to find the optimum levels for stroke length, hold time, and IAD, where the optimum was defined as the level which obtained shot weight closest to the nominal specified value (i.e., label claim of the manufacturer). Using the optimum values, three primed units were actuated ten times each to confirm shot weight delivery. A stroke length of 5.11 mm, hold time of 45.55 ms, and IAD of 30 sec provided shot weight delivery performance closest to the nominal specified value (i.e., label claim of the manufacturer) as shown in  FIG. 17 . Three curves  1705 ,  1710 , and  1715  represent shot weights from bottles  1 ,  2 , and  3 , respectively, in the plot  1700 . 
     Shot weight performance using optimized, automated actuation settings was measured. The shot weight average was 101.9 mg compared to a design delivery target of 100.2 mg. The standard deviation associated with shot weight decreased from 9.2 mg with hand actuation to 4.5 mg across all actuations using automated actuations, a 51.5% reduction. Bottle  3  (represented by curve  1715 ) has the highest standard deviation of 6.19 mg across all actuations. 
     The results of this process indicates that the automated actuation system  800  ( FIG. 8 ) can be used to accurately measure actuation parameters during hand actuation of three nasal spray pumps. Average hand actuation parameters were programmed into the automated actuation system  800 , and the position versus time curves show that the actuator accurately reproduced the ergonomics of hand actuation. Using the automated actuation system  800  reduced the standard deviation associated with shot weight performance from 9.2 mg to 5.9 mg, a 35.9% reduction compared to hand actuation. Within the range of hand actuation parameters, the parameters were varied to optimize the shot weight delivery. The standard deviation associated with shot weight performance was further reduced from 9.2 mg to 4.5 mg, a 51.1% reduction compared to hand actuation. The average shot weight delivery was within 1.7 mg of the target designed delivery value. Determining the actuation parameters may be done prior to conducting any other in vitro measurements, such as spray pattern, plume geometry, or droplet size distribution, to ensure that the automated actuation system  800  consistently simulates hand actuation during these tests. 
     Below are Steps 1, 2, 3, and 4 and subparts thereof that may be used to determine congruency between hand and automated actuation of a spray device  100 ,  400 . 
     Step 1. Determine the minimum number of priming strokes by hand actuation. 
     1.1. Procure the required number of spray pump units filled with drug formulation. 
     1.2. Select one of the units randomly. 
     1.3. Measure the weight of the unit on an appropriate balance or scale, and tare the balance with the unit. 
     1.4. Actuate the unit by hand. 
     1.5. Record the shot weight data (weight of formulation released during actuation) for each actuation and tare the balance between actuations. 
     1.6. Repeat steps 1.2-1.5 for the remaining units. 
     1.7. Analyze the shot weight data from each unit and determine the minimum number of actuations required to obtain stable shot weight performance (e.g., the shot weight being within 95-105% of label claim.) 
     Step 2. Determine the actuation parameter ranges by hand actuation. 
     2.1. Procure the required number of spray pump units filled with drug formulation from the same lot(s) used in Step 1, above. 
     2.2. Select a representative group of people to actuate the units by hand. These people should be trained on how to actuate the units properly, and they should be from a population that corresponds to the age and gender group range for which the product is targeted. 
     2.3. Have each person actuate each unit by hand a representative number of times and record the position vs. time and shot weight data for each actuation. The position vs. time data may be generated with an appropriate sensor and will be used to determine the settings required by the automated actuation system. The shot weight of each actuation may be measured by an appropriate analytical balance or scale. 
     2.4. Calculate the minimum, maximum, average, relative standard deviation (“RSD”), and standard deviation (u) values for each of the automated actuation system parameters plus shot weight, based on the individual actuation recordings. Additionally, compare the calculated shot weight values to the manufacturer&#39;s specifications, if available. 
     Step 3. Determine an initial estimation of delivery performance congruency between hand and automated actuation. 
     3.1. Procure the required number of spray pump units filled with drug formulation from the same lot(s) used in Step 1. 
     3.2. Set the actuation parameters on the automated actuation system to the average values determined in Step 2. 
     3.3. Prime the units using the minimum number of shots determined in Step 1. 
     3.4. Actuate each unit with the automated actuation system a representative number of times. 
     3.5. Record the position vs. time profile and shot weight data for each automated actuation and tare the balance between shots. 
     3.6. Compile the overall average shot weights and RSD&#39;s for the units and compare with those from Step 2. 
     3.7. Qualitatively compare the position vs. time profiles from hand and automated actuation. Additionally, statistically compare shot weights from hand and automated actuation. If statistical differences appear, investigate the scope and make recommendations as appropriate. 
     3.8. The definition for delivery performance congruence will be that the measured shot weight values will be within ±1σ of the values specified by the pump manufacturer. 
     Step 4. Adjust the automated actuation parameters to achieve desired shot weight and determine acceptable ranges. 
     4.1. Procure the required number of spray pump units filled with drug formulation from the same lot(s) used in Step 1. 
     4.2. Set the actuation parameters on the automated actuation system to the average values determined in Step 2. 
     4.3. Prime the units using the minimum number of shots determined in Step 1. 
     4.4. Automatically actuate each unit a representative number of times using the average parameters determined in Step 2. 
     4.5. Record the position vs. time profile and shot weight data for each automated actuation and tare the balance between shots. 
     4.6. Adjust a single actuation parameter (starting with stroke length) in continuous increments of 10% of the average value and repeat Steps 4.4-4.5 until a plateau is reached (10 shot average does not change by more than ±10% of the previous 10 shot average) or until the adjusted actuation parameter is equal to its average value +2σ. 
     4.7. Compile the overall average shot weights and determine the adjusted actuation parameter range as follows: 
     Minimum Minimum value to produce shot weight levels within ±1σ of the average from Step 2. 
     Maximum Maximum value to produce shot weight levels within ±1σ of the average from Step 2, up to the average +2σ. 
     4.8. Repeat the above steps for the other parameters and compile all of the results. 
     While this invention has been particularly shown and described with references to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the invention encompassed by the appended claims. 
     For example, the assembly  600  of  FIG. 6  illustrates the spray device  100  being held in vertical relationship with a foot assembly  620 . However, it should be understood that alternative support techniques may be employed for drug device applications and other applications. For example, the spray device  100  may be held at an angle or horizontally, or even up side down. Further, other embodiments of a shaft  605  and bearing  610  assembly may be employed. For example, the shaft and bearing may be mounted to the spray device  100  as opposed to being in a parallel, off-actuation axis arrangement as shown in  FIG. 6 . Similarly, the linkage  330  described above as extending through the shaft  605  and locking to the shaft head  615  by way of passing through the central hole  635  through the shaft head  615 , may also be clipped onto the bottom of the shaft  605  closest to the transducer  335 . 
     The motor(s) that drive the compression plate assembly  805  in  FIG. 8  may be external from the guide bars  810  or drive rod  830 , as described above, or integral with the guide bars  810  or drive rod  830 . For example, one or more of the guide bars  810  or drive rod  830  may be a threaded screw and be driven by a motor in a worm-gear arrangement with the compression plate assembly  805 , which has a complementary thread in such an embodiment. Another example includes a slot in the guide bars  810  or drive rod  830  with a drive mechanism located inside that is connected to a mating assembly on the compression plate assembly  805 . Further, the automated actuation system  800  may include a mechanism that connects to the mounting assembly  320   c  in a manner adapted to actuate the spray device  100  absent the compression plate assembly  805 . 
     Also, although electrical components (e.g., potentiometer) for measuring displacement or motion of the adapter assembly  315  with regard to the mounting assembly  320  is described herein, other embodiments of transducers may be employed, such as optical sensors (e.g., interferometers) or non-contact electrical sensors, such as hall effect sensors or capacitive probe sensors, where the sensors function in a manner essentially equivalent to a transducer  335 . Similarly, although a transducer cable  340  is illustrated in the embodiment of  FIG. 6 , it should be understood that infrared or Radio Frequency (RF) means for transmitting transducer data indicating position or motion between the adapter assembly  315  and mounting assembly  320  may be employed. 
     With regard to the data collection and processing system of  FIG. 9 , alternative embodiments may be employed. For example, the system  900   a  may not use a signal conditioner  905 ; instead, the system  900   a  may use an amplifier  910  that provides minimal noise or has a signal conditioner  905  integral in the amplifier  910 . Also, various forms of data samplers  915  may be employed. For example, a traditional 12- or 16-bit data sampler  915  may be employed. It should be understood that other data samplers, including non-traditional data samplers may also be used. 
     The transducer  335  may have a draw wire with a stroke length/displacement range of 0-1.5 inches. The electrical output circuitry for the transducer  335  may form a simple voltage divider with the output voltage signal scaling linearly with the absolute position of the draw wire. In addition, the DAQ board  1015  may have a 5 volt DC output that can be used as the input voltage for the transducer  335 , and this sets the 2.5 output range of the sensor to be 0-5 volts DC, corresponding to 0-1.5 inches of displacement, respectively. In addition, this output range is preferably compatible with the input measurement range of the DAQ board  1015 . This DAQ board  1015  may be able to read and record the analog voltage signal  902  from the transducer  335  up 10 kHz or more. In addition, the DAQ board  1015  may be designed to operate in a standard personal computer. 
     A portable or desktop computer system is typically suitable for use with the present invention. The computer system preferably works with the DAQ board  1015  and associated control software. 
     The processor  920  may be a general purpose processor or a specialized signal processor. Similarly, the data acquisition board  1015  of  FIG. 10  may be a specialized data acquisition board operating in a computer or a microprocessor adapted to work within the environment to receive analog or digital information from the transducer  335 . For example, the transducer may be a digital encoder or resolver and provide the information directly as a digital word or data stream. 
     The graphical user interface  1200  of  FIG. 12  may be a text based interface or other form of interface, such as a touch screen. The user may be allowed to select various points along the curve(s) alone or in combination with automated data capture and processing techniques, which include selection of various parameters associated with position, velocity, or acceleration. 
     Control software associated with the present invention may be designed to perform the following functions: (i) record the position vs. time history of the compression and return stroke trajectories; (ii) verify the proper operation of the transducer  335  and DAQ board  1015 ; and (iii) automatically determine the stroke length of the spray device  100 ,  400 , the velocity and acceleration achieved during the compression and return strokes, and the hold time of the stroke (the time spent at the fully compressed position). 
     The curves of  FIGS. 14-17  are indicated for three users. However, it should be understood that many more users of the spray device  100 ,  400  may be involved in the testing to make more accurate measurements and determine accurate parameters. Further, persons of multiple age groups, sizes, hand sizes, health, hand impairments (e.g., carpal tunnel syndrome), and other criteria may be used in the testing and actuation characterization process. 
     Image Therm Engineering, Inc.&#39;s (Sudbury, Mass.) SprayVIEW NSx, MDx, and OSx automated actuation systems are examples of automated actuation systems  800  of  FIG. 8  suitable for use with the present invention. These systems allow programming of stroke length, compression and return stroke velocity and acceleration, and hold time levels. The output from the processor  920  may be used directly as inputs to these systems, thus allowing a simple transition from the required exploratory studies to automated actuation to be achieved and documented. In addition, the assembly  600  could be used simultaneously with these automated systems to verify their proper operation. 
     It should be understood that any of the data collecting or processing may be implemented in hardware, firmware, or software. If implemented in software, instructions may be stored on computer-readable media, such as magnetic disk, optical disk, read only memory (ROM), random access memory (RAM), loaded on a server and transmitted across a computer network, or stored on any other form of computer readable medium. A processor loads the software instructions from the computer-readable medium and executes the instructions to perform the processes described herein. 
     The assembly  600  may be used to record the position vs. time trajectories achieved during actuation of pharmaceutical spray pump assemblies and also for other applications. Examples of other applications include the following: characterization of glue/caulking guns, household spray pumps, pressurized spray cans, and pharmaceutical nasal syringes; testing of robotic actuation of industrial nozzles; and/or actuation of cosmetic spray pumps.