The morphology of monoclinic paracetamol crystals has been investigated both theoretically and experimentally. Calculations using the computer program HABIT 95 with both DREIDING II and MOMANY force fields predict prismatic forms in which {100}, {001}, {110}, and {201̄} show approximately equivalent morphological importance. Whereas all of these faces are observed experimentally, the real crystals showed a {110} dominance at low supersaturations which gave way to an increasing {001} dominance as the supersaturation increased. This variation was accompanied by a change from a columnar to a platelike habit. Surface examinations using phase contrast microscopy showed the habit changes to be due principally to changes in the growth mechanism of the {110} faces. A slow growth process involving two-dimensional nucleation at a few growth sources occurred at low supersaturations. This gave way to dislocation growth and finally at high supersaturations, to a fast growing mixed mechanism combining two-dimensional growth from the edges and vertexes of the {110} faces with the operation of dislocation sources at the face center. The increasing dominance of the two-dimensional growth contribution at the highest supersaturations coupled with an increase in macrostep formation resulted in the development of inclusions in the {110} sectors. This phenomenon will result in significant increases in the solvent impurity content of crystals at the high supersaturations normally used in the production of this material. The results of this study show well the dominant part that the growth mechanism can play in the definition of the morphology of crystals and hence the care which must be taken in the interpretation of modeling calculations.

When dissolved in aqueous solution, R-lactose, whether originally in the anhydrous or the monohydrated form, readily undergoes mutarotation to yield the β isomer. At equilibrium, which is reached in 6.5 h at 292 K and more rapidly with increasing temperatures, the latter is present to the extent of ca. 60% w/w. At saturation, R-lactose hydrate precipitates from this solution being considerably less soluble than the β form. The resulting crystals have a highly asymmetric, tomahawk shaped morphology characterized by large {01 h1} faces. It is confirmed that this shape arises from growth inhibition due to the incorporation of the β isomer in the {01 h1} sectors of the crystals coupled with a characteristic lack of growth in the [01 h0] direction. Growth under conditions that restrict the formation of the β isomer yields more symmetrically shaped, needlelike crystals. These show a gradual transition to the tomahawk shape as the concentration of the β isomer in solution and hence in the crystal is increased. An assessment is made of the degree of incorporation of the β isomer into the crystal, its distribution and its influence on the defect structure of the material.

The crystallization behavior of tripalmitin (PPP) and trilaurin (LLL) without and with the application of ultrasonic power is investigated in situ using synchrotron radiation time-resolved small-angle X-ray scattering (SAXS) and wide-angle X-ray scattering (WAXS) simultaneous measurement. Without ultrasound application, both polymorphic forms β′ and β crystallized in the melt of each substance. With ultrasound treatment of the melt, the following effects were observed: (i) a marked decrease of induction times for crystallization of both PPP and LLL, (ii) an increased nucleation rate, and (iii) a crystallization of only the β form for both PPP and LLL under conditions of initial crystallization temperatures of 50 and 30 °C, respectively, and applied ultrasound of 2 s. The last finding demonstrates that ultrasound irradiation can be used as an efficient tool for controlling the polymorphic crystallization of fats. In addition to this, the crystallization of LLL under a lower initial crystallization temperature of 25 °C and with the same ultrasonication time of 2 s, revealed the presence of both β′ and β polymorphs. This suggests that the crystallization of only the β form depends not only on ultrasound treatment but also on the initial temperature of crystallization. On the basis of the dynamic nucleation of PPP and LLL crystals induced by collapsing caviatation bubbles, we argue that a pronounced decline in induction times and an increase in the nucleation rate result from the shift in the melting points due to high-pressure pulses associated with collapsing bubbles. The insufficiency of this approach in accounting for the nucleation of only the β polymorph or both β′ and β polymorphs was also considered.

The growth morphology of monoclinic paracetamol as a function of the supersaturation is determined using Monte Carlo simulations based on the crystal structure. The results are compared with experimental results reported recently on both the morphology and the relevant growth mechanisms. The change of an elongated to a more bulky habit with increasing supersaturation is reproduced well by the simulations. The method used opens ways to predict the crystal morphology for real crystal structures in dependence of supersaturation once information on the relevant growth mechanism for the various faces is known.