Physicochemical characterization of d-mannitol polymorphs: The challenging surface energy determination by inverse gas chromatography in the infinite dilution region

Abstract

Nowadays, it is well known that surface interactions play a preponderant role in mechanical operations, which are fundamental in pharmaceutical processing and formulation. Nevertheless, it is difficult to correlate surface behaviour in processes to physical properties measurement. Indeed, most pharmaceutical solids have multiple surface energies because of varying forms, crystal faces and impurities contents or physical defects, among others. In this paper, D-mannitol polymorphs (α, β and δ) were studied through different characterization techniques highlighting bulk and surface behaviour differences. Due to the low adsorption behaviour of β and δ polymorphs, special emphasis has been paid to surface energy analysis by inverse gas chromatography, IGC. Surface energy behaviour has been studied in Henry's domain showing that, for some organic solids, the classical IGC infinite dilution zone is never reached. IGC studies highlighted, without precedent in literature, dispersive surface energy differences between α and β mannitol, with a most energetically active α form with a γ(s)(d) of 74.9 mJ·m⁻². Surface heterogeneity studies showed a highly heterogeneous α mannitol with a more homogeneous β (40.0 mJ·m⁻²) and δ mannitol (40.3 mJ·m⁻²). Moreover, these last two forms behaved similarly considering surface energy at different probe concentrations.

Formulation and characterization of biocompatible and stable I.V. itraconazole nanosuspensions stabilized by a new stabilizer polyethylene glycol-poly(β-Benzyl- l -aspartate) (PEG-PBLA)

“…However, the pattern of peaks observed in the lyophilized samples was different to that from the crude ITZ. It has been shown by others (Cares-Pacheco et al, 2014;Grohganz et al, 2013;Kaialy and Nokhodchi, 2013;Lee et al, 2011) that the excipient mannitol is crystalline after lyophilized and our own results also showed this (data not shown). The contribution from mannitol in the ITZ-PBLA-Nanos explains why the peak pattern of the ITZ-PBLA-Nanos was different from that of the crude ITZ.…”

The Effect of Polymorphism on Surface Energetics of D-Mannitol Polymorphs

“…Polymorphic identity of the crystals obtained in this study was confirmed by comparing the PXRD pattern of different crystals obtained in this study with the predicted diffraction patterns that were generated using Reflux module in Materials Studio 5.5 (Accelrys Software Inc.). Furthermore, PXRD patterns obtained in this study for different polymorphs of D-mannitol was also compared with literature confirming the presence of all three different polymorphs of D-mannitol (16,33). The powder pattern of α polymorph was characterised by peaks at 2θ values 9.5°, 13.8°, and 17.4°.…”

“…Solvent and humidity induced transformation of crystal forms and limited success in reproducibly preparing different polymorphs has hindered the progress. Recently, CaresPacheco, et al have reported the surface energy heterogeneity of different polymorphic forms of D-mannitol (16). β and δ polymorphs of D-mannitol were reported to be energetically homogeneous, whereas α polymorphs was found to be energetically heterogeneous.…”

“…β and δ polymorphs of D-mannitol were reported to be energetically homogeneous, whereas α polymorphs was found to be energetically heterogeneous. Furthermore, surface energy differences between β and δ forms were reported to be nonsignificant compared to α form (16).…”

Combined control of morphology and polymorph in spray drying of mannitol for dry powder inhalation

“…It is worth noting that the solute may not instantly crystallize while the saturation is satisfied at the surface of the droplet. Interestingly, the rate of nucleation and crystal growth determine the time to crystallization in the solution [48]. Indeed, gas bubbles can have a positive effect on crystallization, as commented by Nakamura [49], Matsumoto [50] and Deora [51].…”