Small-Angle X-ray Scattering for Pharmaceutical Applications - Pharmaceutical Technology

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Small-Angle X-ray Scattering for Pharmaceutical Applications
The author describes the development of small-angle X-ray scattering and analyzes its advantages in the characterization of drug-delivery systems and large molecules. This article is part of a special Analytical Technology issue.

Pharmaceutical Technology
Volume 34, pp. s32-s37

Technical concepts

The main technical challenges of SAXS are to separate the strong primary X-ray beam from the weak scattering information close to the primary X-ray beam and to increase the intensity of the scattered X-rays.

Figure 2: A typical setup for a small-angle X-ray scattering instrument includes a source, collimation system with optics (i.e., mirror), sample holder, and detector. The area that the beam enters after passing the mirror is typically evacuated to reduce unwanted scattering from gas molecules.
Scientists have used different concepts to achieve these goals. However, all SAXS instruments feature an X-ray source, a collimation system focusing optics, a sample holder, a beam stop, and a detector (see Figure 2).

X-ray sources

To date, copper anodes, producing Cu–Kα radiation, have been the best compromise between sensitivity and absorption. The following three technologies are currently in use:

  • Sealed-tube sources
  • Rotating-anode sources
  • Microfocus sources.

In sealed-tube sources, the electrons are accelerated toward a fixed anode. Part of the energy is emitted as X-rays, but the majority is converted to heat. In sealed-tube sources, the anode is fixed, so a limited amount of energy can be dissipated before the copper melts. Rotating-anode sources exceed this limit and avoid local overheating (5).

Microfocus sources use electromagnetic lenses to focus the electron beam to a fine point, thus producing a high-brilliance X-ray beam.

Scientists typically consider operating costs, energy consumption, and flexibility when choosing an X-ray source. They also must determine whether the source will match with other components of the SAXS system.

X-ray optics and collimation systems

Focusing optics increase the photon flux through the sample. Visible-light lenses and electromagnetic fields such as electron beams cannot focus X-rays. Multilayer mirrors reflect X-rays on a layered surface under the Bragg condition (see Equation 3). Depending on the layers' thickness, a certain wavelength positively interferes (i.e., reflects) at a specific angle (5).

By reflecting certain wavelengths at certain angles, multilayor mirrors can produce monochromatic X-rays. The mirror's curvature produces the desired beam focus, typically parallel or converging.

The monochrome and focused beam then travel through the collimation system to produce a precise beam profile. The following two collimation methods are common:

  • Point collimation (i.e., a pinhole system)
  • Line collimation (i.e., a slit system).

Point-collimation systems send a point-shaped beam through a series of three pinholes. The first two pinholes produce a parallel beam, and the third pinhole blocks unwanted scattering produced by previous pinholes.

Line-collimation systems use a line-shaped beam and employ slits instead of pinholes. The block collimator, a compact and effective design to eliminate parasitic scattering by the collimation system itself, was suggested by Kratky (4).

Figure 3: Scattering patterns of silver behenate. The liquid crystalline structure with clear concentric rings in the case of a point-shaped beam profile (i.e., point collimation) (right) becomes smeared when using a line-shaped beam (i.e., line collimation) (left). The line-collimated experiment yields higher intensity. Reversing the smearing effect requires knowledge of the beam profile and position.
Line collimation increases the photon flux through the sample by replacing a single point-shaped beam with the equivalent of many such points arranged in a line. The increase in intensity comes at the cost of a smearing effect on the scattering image (4). Figure 3 shows the effects of line collimation.

Desmearing data is a mathematical operation that requires knowledge of the beam profile that causes the smearing effect (6–8). New technologies report the beam profile and position so that desmearing becomes a simple and precise routine, thus alleviating earlier concerns (9, 10).


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