The key feature of acoustic micro imaging (AMI) is its ability to image internal bonds in materials rapidly and nondestructively. For many applications in the production of drug delivery appliances or systems, AMI is used to determine whether two materials (ie, a tube within a tube) are well bonded. In some applications, the focus is on determining whether a given material, such as a polymer, is truly homogeneous or whether it contains defects, such as voids.

Use of VHF (frequencies up to 100 MHz) and UHF (100+ MHz) ultrasound to conduct nondestructive internal inspection has advanced rapidly since its inception 30 years ago at Sonoscan (www.sonoscan.com). Current AMI systems achieve very high spatial resolution in images made using a very broad range of ultrasonic frequencies. They are also capable of carrying out acoustic imaging in several different modes, including three-dimensional acoustic imaging, virtual cross-section imaging, and others.

The driving force in the AMI inspection of bonded materials is product reliability. Whether the product is a foil pouch containing refill cartridges for an inhaler or a system for direct intravenous delivery of a drug, the manufacturer generally wants to know whether materials that are supposed to be bonded are in fact bonded, and whether the bond will meet all of the handling and usage reliability requirements of the product. For example, will the bond joining an IV line to a polymer bag stand up to prolonged storage under varying conditions and still function without failing or leaking? Will a foil pouch maintain a tight seal to prevent oxygen and humidity from reaching the contents of the pouch?

HOW AMI IMAGES MATERIALS

A moving ultrasonic transducer raster scans the sample of interest (ie, a foil or polymer pouch). While moving, the transducer pulses bursts of ultrasound into the sample; the ultrasound travels into the pouch and is reflected by internal material interfaces. The return echo signals reflected from interfaces arrive back at the transducer for collection in a fraction of a microsecond; the entire round trip may last only 100 nanoseconds. The transducer can therefore scan rapidly while carrying out several thousand pulse-and-receive iterations per second.

Not all interfaces interact with the pulse of ultrasound in the same way. If two materials are well bonded, a portion of the pulse is reflected from the bonded interface as an echo. Each of the two materials has an acoustic velocity (the speed at which sound travels through it) and a density; the product of these two values gives the acoustic impedance of each material. If the difference in acoustic impedances between two materials is small, the reflection will be modest. If the difference in acoustic impedances is large, the reflection will be large. Generally, though, a significant portion of the pulse passes through the interface, travels deeper, and is reflected at the next deeper interface the degree of reflection again depending on the local difference in acoustic impedances (Figure 1).

GAP-TYPE DEFECTS

This process is greatly altered by the presence of a gap. Gaps are filled with air or another gas, whose density is so low that the difference in acoustic impedance between the gap and the adjacent solid material is extreme. Virtually all of the incoming pulse is reflected by a gap, even if the gap is only 1000Å thick or less. Engineers wanting to know whether their production processes have yielded well-bonded interfaces use AMI to ensure that the interfaces are free from delaminations, cracks, and voids.

Although the transducer scans the x-y area of the sample, the sample itself is not necessarily flat. Many samples, such as the seals on pouches, are flat, but AMI can also image many cylindrical samples. The transducer scans one longitudinal line at a time along the cylindrical sample to produce a flat image of the internal bond. The weld or bond of a smaller tube within a larger tube is an example of this type of scanning.

HIDDEN DEFECTS THREATEN RELIABILITY

Figure 2 is the C-SAM® acoustic image of the seal at one edge of an IV bag. The seal in this case is between two layers of polymer, and gray areas of the image indicate the moderate degree of reflection one would expect from a good bond that reflects only a portion of the ultrasonic pulse. Bright white areas (arrows) indicate the very high degree of ultrasonic reflection associated with a delamination. In these areas, the two layers of polymer are not bonded.

Not all of the reflected echoes from the sample were used to make the acoustic image in Figure 2. Typically, only the echo signals from the "depth of interest" (in this instance the depth at which the two layers are bonded) are processed for the acoustic image, while echo signals from other depths are discarded.

A small foil-on-foil single-dose drug package is shown in Figure 3. The contents of the package are at center; because this portion of the package is effectively a huge gap, it reflects ultrasound brightly. The package contents are not visible because very high frequency ultrasound does not travel well through a gas. The perimeter of the package should display an unbroken seal. That is, it should be evenly dark in this imaging mode. But the seal actually contains numerous areas that have the same acoustic profile as the content area of the package - they are filled with air and are potential pathways for contamination to reach the content area. None of the elongated voids seen here actually reaches the outside, but some of them nearly do (see circle in Figure 3). This is a good example of a package in which drifting process parameters have produced bonds that look normal optically but whose internal defects become apparent when viewed with ultrasound.

CYLINDRICAL SAMPLES

A cylindrical sample (in this case, a circular plastic element welded inside a larger cylindrical plastic element) is shown in Figure 4. The assembly was mounted horizontally. The ultrasonic transducer makes one longitudinal scan, and the assembly is then rotated to accommodate the next longitudinal scan. In the acoustic image, the sample appears "unrolled." Cylindrical samples are sometimes rotated slightly more than 360° to make the same acoustic features appear at the very top and the very bottom of the acoustic image. Because of its large size, this sample was rotated less than 360° to create this image.

The "depth of interest" in this case is the interface between the two plastic elements, in which an inadequate weld could lead to leakage during dispensing of the liquid drug product. The acoustic image in this case presents the circular weld zone "unrolled" as a flat image.

The red and black areas to the right and left are intentional air gaps at either side of the weld. In these areas the two interfaces curve upward (on the left) or downward (on the right). The weld area itself is between the two areas, and is light gray, indicating that the critical area was welded successfully, and has a good bond. A few materials are not good subjects for AMI. The most frequently encountered unsuitable material is paper, or paper-like synthetic materials. They cannot be imaged because paper is filled with small internal gaps that (just like defects) reflect ultrasound. But a material, such as a polymer bonded to paper, can be imaged from the polymer side.

The techniques described here are used both in development and in production for a wide variety of drug delivery devices. Acoustic micro imaging provides highly accurate data on the condition of internal bonds in applications in which alternate methods, both destructive and nondestructive, are either not suitable or are lacking in sensitivity. The vast majority of production materials (metals, polymers, ceramics) are easily imaged and provide engineers with a nondestructive insight into the internal bonds on which the reliability of their products depend. They also simplify the establishment of accept/reject criteria for critical drug delivery products.

BIOGRAPHY

Tom Adams is a freelance writer and photographer based in New Jersey. He has written more than 500 articles for technical and scientific trade magazines. His articles have appeared in more than 50 magazines in 15 countries in North America, Europe, and Asia. He can be reached at 20 Devon Avenue, Lawrenceville, NJ 08648; phone: (609) 883-5040; fax: (609) 883-5087; e-mail: teadams@earthlink.net.