Regulating particle morphology during a spray freeze drying ...

LIGHT‐SCATTERING 313.2.6 Instrumentation and limitation of DLSDLS requires higher solute concentrations than static LS. Particles larger than 5 μmcannot be measured by QELS, due to sedimentation effects [Demeester et al. 2005].When static and dynamic LS‐detectors are combined and r G and r H are measured,derivation of the particles shape and compactness can be made [Kok and Rudin 1981].Figure 17 shows two different types of macromolecule shape.a) b)Figure 17. Molecular conformation: two different molecular shapes: a) solid sphereand b) voluminous molecule with three salient side chains. Modified pictures fromWyatt [2006b]For compact particles, r G is smaller than the hydrodynamic radius. The ratio between thetwo different radii (r G / r H ) therefore is smaller than unity, and lower than the ratio for amore extended particle.3.3 Different separation techniquesWhen a polydisperse sample is analyzed using a separation technique, the sample isdivided into its monodisperse fractions each characterized by its size or molecularweight. Two separation techniques that are commonly used are size exclusionchromatography and asymmetrical field flow field fractionation [Philo et al. 1996].LS‐detectors are always connected to an UV‐ or RI‐detector that are commonlyused as concentration detectors. If the value of dn/dc is known, light scattering canprovide an absolute measurement of the molar mass of macromolecules withoutknowing any other sample information. Thus light scattering can provide a continuousmeasurement of the molar mass if the sample concentrations are high enough toprovide adequate signals.