Spherical agglomeration technology can produce high‐performance spherical particles in a single crystallization unit, although it is still challenging to control the particle size and shape. To solve this issue, a two‐step bridging (TSB) mechanism containing a preconditioning period, size period, and shape period is proposed. The dynamic balance among the forces of adhesion, dispersion, and capillary action in the multi‐liquid phases plays a key role. This is fully considered to establish the TSB‐based thermodynamic size model and particle design framework by weighting the force action regions in multi‐liquid phases with dynamic composition. The spherical agglomerates of benzoic acid, celecoxib, and salicylic acid with narrow particle size distributions and tunable particle size ranges of 2000–5000, 800–3500, and 1500–4500 μm, respectively, were designed and prepared successfully, showing good correlation with the calculation, which is superior to the reported methods and indicates that the mechanism has certain universality and guiding significance.
In harsh environmental conditions, the relative orientations of transmitters of rotary-laser scanning measuring systems are easily influenced by low-frequency vibrations or creep deformation of the support structure. A self-compensation method that counters this problem is presented. This method is based on an improved workshop Measurement Positioning System (wMPS) with inclinometer-combined transmitters. A calibration method for the spatial rotation between the transmitter and inclinometer with an auxiliary horizontal reference frame is presented. It is shown that the calibration accuracy can be improved by a mechanical adjustment using a special bubble level. The orientation-compensation algorithm of the transmitters is described in detail. The feasibility of this compensation mechanism is validated by Monte Carlo simulations and experiments. The mechanism mainly provides a two-degrees-of-freedom attitude compensation.
Granulation
is an important method to increase the fluidity
of
compounds, especially drugs with needle-like shapes. Another function
of granulation is to mix active pharmaceutical ingredients (APIs)
and excipients. In this research, oiling-out spherical agglomeration
technology was used to obtain single- and multicomponent drug spherical
particles of gemfibrozil, which can be directly compressed. This technology
is carried out by simply heating and quenching operations in nonorganic
solvents. Compared with the current granulation technology, it is
estimated that approximately 400 metric tons (MT) of organic solvents
per year can be saved for every 100 MT of gemfibrozil production.
Meanwhile, based on the binary oiling-out phase diagram, the spherical
particles of gemfibrozil were prepared with high bulk density (0.71
g cm–3), good sphericity (>80%), high yield (>95%),
and adjustable particle size distribution, and the flowability is
improved by 47.37%. Furthermore, the multicomponent functional particles
of gemfibrozil and nimodipine for drug combination with the good morphology
and uniform distribution of components were obtained by establishing
ternary oiling-out phase diagrams. The results of tablet compaction
showed a 4 times increase in tabletability from single-component spherical
particles and a 2.7 times increase from multicomponent spherical particles
compared to commercial powders. On the other hand, the failing case
of gemfibrozil and simvastatin indicated that the binding energy between
molecules is the key point of this method, and this result revealed
the limitation of the oiling-out spherical agglomeration method for
the current selection strategy of drugs. This work provided an experimental
and theoretical basis for the further application of this green technology.
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