The pharmaceutical industry uses successfully both FT-NIR and Raman microscopy to produce chemical images of solid dosage forms, typically in troubleshooting roles. However, due to the chemical composition of the formulations, it is not always possible to describe the entire chemical formulation by using a single spectroscopic method. As Raman and NIR spectroscopies are complementary in nature, their combined usage offers the opportunity to describe heterogeneous mixtures in more detail. A novel sample referencing approach has been developed that allows data to be acquired from exactly the same area of the sample using both Raman and FT-NIR microscopies. The optimum images for the components are then overlaid, which gives rise to a combined chemical image that visually describes the entire formulation. We have named this approach chemical image fusion (CIF). CIF has been applied to two examples. The first shows how a simple formulation was used to validate the CIF approach. In the second, CIF allowed an entire formulation to be visualized and the cause of tabletting problems determined. CIF provides increased confidence in the results generated by each individual technique and offers a more powerful method for the evaluation of pharmaceutical formulations.

Extended classical nucleation theory predicts that heterogeneous crystallization on a convex substrate will be less efficient than for the planar case. In this article, we present the first systematic study of the effects of interfacial curvature on crystallization. Decane-in-water nanoemulsions and emulsions have been prepared with droplet sizes of ∼67 nm, ∼280 nm, and ∼1.9 µm, which are stabilized by the passive nonionic surfactant, Brij 30. Ice nucleation is induced at the curved decane-water interface by 1-heptacosanol, which can cause ice formation at temperatures as high as -4.5 to -7 °C at the corresponding planar interface. Differential scanning calorimetry and optical microscopy data show that the ∼280 nm and ∼1.9 µm droplet systems induce ice formation at temperatures up to -8 ( 2 to -9 ( 2 °C, for 1-heptacosanol interfacial concentrations of ∼2-8% and ∼4-11%, respectively. In comparison, ice nucleation only occurs at temperatures up to -13 ( 2 °C in the ∼67 nm droplets, which have higher interfacial 1-heptacosanol concentrations of between ∼9 and 21%. The extended classical nucleation theory is insufficient to explain the extent of the reduced nucleating ability in the ∼67 nm nanoemulsions, and so we propose that the nucleating ability of 1-heptacosanol is also reduced as the interfacial curvature increases.

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On page p2160, right-hand column, fourth row from the top, ref 19 should be ref 20.

Highly anomalous crystallization behavior has been achieved in phase-inverting emulsion systems by using nonionic surfactants that induce nucleation. In particular, nucleation can be inhibited at the phase inversion, allowing systems held at, or near, this temperature to undergo crystallization either on heating or cooling. This new phenomenon is demonstrated for 27.4 wt % aqueous glycine solutions emulsified in decane using Span 20 Tween 20 blends. The inhibitory effect on interfacial nucleation at/near the phase inversion is readily shown by the maximum in the induction time for crystallization found in systems at/near the phase-inversion temperature. These findings are unprecedented. An extremely rapid rise in nucleation rate is expected on cooling glycine solutions, owing to the associated increase in supersaturation, the driving force for crystallization. The origin of this highly anomalous behavior is thought to be the low droplet interfacial tension, gammaow, that occurs at the phase-inversion temperature, which results primarily in a substantially increased contact angle between the glycine critical nucleus and the droplet interface. This may present a paradigm shift in crystallization strategies through the use of tunable contact-angle nucleators.