•Micro-XCT technology was applied to monitor the crystallization.•A force-field modeling with habit calculation confirmed the formation of polymorphisms.•Micro-XCT utilization allowed to measure ...nucleation and growth rates of Paracetamol.•A segmentation algorithm was tuned to identify single crystals from aggregates.•Molecular modeling was used to identify crystal faces to measure independent growth rates.
This work highlights the capabilities and limits of X-ray computed tomography in crystallization monitoring through a use case involving paracetamol as the solute, recrystallized from ethanol, methanol, or a mixture of both. The cooling crystallization operation was set up in two different containers, prepared with cotton yarns stretched vertically, acting as linear nucleation sites that immobilize the grown crystals in the recording area. The largest container (10 mL test tubes) allowed the acquisition of a larger number of crystals (up to 300 particles) for a more appropriate bulk analysis. The smallest container (5 mL pipette tips) allowed for a finer resolution of the recorded solid phase at the expense of a reduced recording volume. Crystallization was monitored in terms of the number of individual crystals, their size, and the overall volume, thus leading to the nucleation and growth rates, and solid-phase production rate. The main benefit of X-ray computed tomography is in the 3D analysis of the reconstructed solid phase. The crystal habit of paracetamol form I was predicted using force-field modeling. The predicted habit was in great accordance with the reconstructed solids, confirming the polymorphic form. Furthermore, face-specific growth rates of reconstructed crystals were measured, paving the way for a novel approach to the investigation of crystal-solvent interactions.
To investigate how the fat crystal structure affects lipid in vitro digestibility, 30% palm stearin-in-water emulsions were prepared after storage at different temperatures (4, 25, and 37 °C) for 1 ...h, which consisted of different polymorphic forms, sizes, and quantities of fat crystals. The variation of particle size (d 4,3), zeta potential, and microstructure during the gastrointestinal digestion and the free fatty acid (FFA) released in small intestine phase were investigated. After oral and gastric digestion, all of the emulsions underwent partial or complete coalescence and flocculation. During intestinal digestion, the d 4,3 and zeta potentials did not notably affect lipid digestion. The FFA-released assay results indicated that the lipid digestion extent decreased as the fat crystal size and content of the β polymorph increased, and there was no obvious relationship between FFA release and fat crystal quantity or solid fat content (SFC). This study highlighted the crucial roles of fat crystal size and polymorphic form in regulating the digestion behavior of lipid-based O/W emulsions.
•The different crystalline oil-in-water emulsions were fabricated.•The digestion behaviors were investigated using an in vitro digestion model.•The relationship between fat crystal structure and FFA ...release were characterized.
The effects of the fat crystal structure on lipid droplets digestion behaviors were investigated using an in vitro digestion model. The crystalline oil-in-water emulsions containing the same solid fat content (SFC) with different fat crystal sizes and polymorphic forms were fabricated by different storage protocols: constant-temperature and inconstant-temperature storage. Oral and gastric processing led to a significant increase (p < 0.05) in the d4,3 values of the two emulsions, and the two emulsions underwent partial coalescence and flocculation/aggregation. The free fatty acid (FFA) release profiles showed that the lipolysis extent decreased due to a larger crystal size. In addition, the two emulsions showed differences in beta polymorphism. This work further demonstrated that the FFA release could be modulated by the physical properties of the fat.
The aims of this study are to determine the physicochemical properties and to quantify the fractal dimension of refined, bleached and deodourised palm oil (RBDPO) crystal network using image analysis ...and rheological methods during four weeks of storage at 15, 20 and 25 °C. There was no progressive increase in solid fat content (SFC) after one week of storage. X-ray diffraction indicated RBDPO stabilised in the β′ polymorphic form without transformation to β polymorph upon storage. However, photomicrographs of the crystal networks showed new small crystals formation in between the crystal clusters and on the surface of the existing crystals. The fractal dimensions of RBDPO crystal networks by image analysis (Db) and rheological measurements (Df) increased from day 1 to week 4 of storage. The results also showed good agreement between (Db) and (Df) in quantifying the hardness, storage modulus (G′) and mass distribution of RBDPO crystal networks during storage.
•The study indicated palm oil recrystallised without polymorphic transformation.•Recrystallisation due to secondary nucleation change the viscoelasticity of PO.•Fractal dimension of the crystal networks increased during storage.
Generally, DPI formulations show low fine particle fraction (FPF) due to poor detachment of drug particles from carrier during inhalation. l-Leucine, with varying concentrations (ranging from 0 to ...10% w/w), were introduced into a 60%w/v mannitol solution where the solutions were then spray dried to achieve a new processed carrier. The spray dried samples were blended with Albuterol sulfate to determine the efficacy of their aerosolization performance. Analyzing each formulation was completed via the implementation of numerous analytical techniques such as particle size distribution analysis via laser diffraction, differential scanning calorimetry (DSC), scanning electron microscope (SEM), powder X-Ray diffraction (PXRD), Fourier transform infrared (FT-IR) spectroscopy, and an in vitro deposition study. It was shown the concentration of leucine in spray dried is really crucial to achieve the highest FPF possible. The highest FPF was obtained for the samples containing 10% w/w leucine which was 52.96 ± 5.21%. It was interesting to note that the presence of leucine produced different polymorphic forms for mannitol. Moreover, through this study, the authors were able to conclude that mannitol can serve as an alternative carrier in DPI formulations containing Albuterol sulfate tailored for lactose intolerant patients.
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•The use the inulin as surfactant agent in compound chocolate was proposed.•The shelf-life was improved achieving greater stability against degradation processes.•The sample with inulin at 10% (w/w) ...show a dense matrix structure.•The bloom formation was delayed with lower size and number of fat crystals.•This chocolate also showed less fracturability and improved thermal properties.
The effect of the addition of inulin as a surfactant or stability agent on white compound chocolate sweetened with sucralose and Stevia was studied. Samples were stored at 7, 15 and 30°C during 100days and the influence of inulin on rheological properties, sensorial attributes, shelf-life, physical properties such as melting, crystallization and blooming were analyzed. The shelf-life of the compound chocolate with the incorporation of inulin was higher than the control sample without replacement. Compound chocolate with inulin at 10%w/w showed a dense matrix structure, reducing the size and number of fat crystals formed during storage; furthermore they presented higher values of brightness and WI. This chocolate also showed less fracturability and improved thermal properties. DSC studies revealed increased values of onset and peak temperatures and enthalpy of melting of the polymorphic form V, at higher storage temperatures, achieving greater stability against degradation processes.
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Segesterone acetate (SA) is a promising and recently approved drug substance used as a contraceptive. SA has two major polymorphic forms, Form I and II. We have shown through indirect ...analysis that Form I is the more thermodynamically stable polymorphic form at room temperature, however, during the manufacturing process of SA drug products the solid-state stability must be shown to be under control. In the present work, a systematic study has been done using X-ray powder diffraction (XRPD), Fourier Transformed Infrared spectroscopy (FT-IR), and room temperature Raman spectroscopy on both micronized and non-micronized SA powder samples. XRPD showed a crystalline structure in both powder samples with a distinct coexistence of the polymorphic Forms I and II which was confirmed by FT-IR and Raman spectroscopy. The study showed that after thermal annealing a noticeable reduction of the amount of polymorphic Form II was found in both samples. Our results suggest the possibility of reducing the amount of SA Form II by thermal treatment inducing an irreversible solid-state transition to yield the thermodynamically more stable polymorphic Form I. To quantify the ratio of polymorphs I and II we have implemented a method that can be used as a routine analysis step in the manufacturing process of SA.
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•Etoposide micro-particles were prepared using SEDS process.•A reduction in the particle size led to an increase in the dissolution rate.•A new polymorphic form of etoposide was ...discovered and characterized.•The new polymorphic form exhibited higher solubility and faster dissolution rate.
To improve the solubility and dissolution rate of etoposide, micro-particles were prepared using solution-enhanced dispersion by supercritical CO2, and the transition of crystal form was investigated using scanning electron microscopy, X-ray diffraction, thermogravimetric analysis, and differential scanning calorimetry. The effects of various operating parameters, including precipitation pressure, temperature, the etoposide concentration, and solution flow rate were investigated. The results showed that the particle size of etoposide can be controlled, and smaller particles of 586nm were successively obtained. A reduction in the particle size led to an increase in the dissolution rate. Furthermore, at a precipitation pressure ≥18MPa, a new polymorphic form was discovered, which exhibited higher solubility and faster dissolution rate.
Although the amount of amorphous content in lactose is low, its impact on the performance of a dry powder inhalation formulation might be high. Many formulators and regulatory agencies believe that ...the levels of amorphous content should be controlled once there is a relationship with the final product performance. This is however not an easy task. The current paper elaborates on multiple challenges and complexities that are related to the control of the amorphous content in lactose. The definition and quantification methods of amorphous lactose are reviewed, as well as challenges related to thermodynamic instability. Additionally, current monographs and recent position papers considering this parameter are discussed to provide an overview of the regulatory landscape. Development of a control strategy is recommended, provided that the amorphous content at a specific moment in the process has shown to have an impact on the performance of the dry powder inhaler.
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•The attention of regulatory agencies and formulators to amorphous content has increased.•The apparent amorphous content in lactose is difficult to define.•Different quantification methods can result in different values.•The apparent amorphous content can be unstable over time.•Control strategies should only be developed when the amorphous content has an effect on the final product performance.
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