Methods
Preparation of the minitablets.
TH, Avicel PH 102, spray-dried lactose, and magnesium stearate in four different ratios (total 4 kg per batch) were blended
using an IMA Cyclops blender (IMA, Ozzano, Italy).
Figure 1: Special tooling for minitablets (IMA, Ozzano, Italy). (FIGURE COURTESY OF THE AUTHOR)
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Direct compression was performed using a tablet press machine for research and development and small batches (IMA Pressima
equipped with 2 EU-D punches fitting 24 minipunches, 2 mm diameter each, (see Figure 1). Compression force used to obtain
9 mg minitablets was maintained at 20 kN for all batches with fill-shoe speed adjusted to 25 rpm.
Table I: Comparison of the two coating formulas.
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Coating of minitablets
. The coating process of 10 kg of minitablets for each batch was carried out in an IMA GS 25-L solid wall pan (see Figure
2). Two different coating formulas were used (see Table I): a traditional one containing single components to be previously
dispersed in water (A) and the ready-to-use pigment dispersion WAS (B).
Figure 2: Schematic of the solid-wall coating pan. (FIGURE COURTESY OF THE AUTHOR)
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Coating dispersion A was prepared by homogenizing, in a separate vessel, pigments, plasticizer, and part of the solvent for
10 min. The dispersion obtained was then added to a main vessel containing Eudragit RL/RS and the remaining water and stirred
continuously. Coating dispersion B was prepared by simply adding WAS to the main vessel containing Eudragit RL/RS and solvent
without the need of predispersion. The coating suspension was than stirred continuously. Both formulas were tested at different
polymer amounts expressed in total solids' weight-gain percentage.
The coating process was started by loading the minitablets in the pan manually and without any drum rotation. A preheating
phase was carried out at the minimum drum speed to ensure the proper temperature of the cores prior to the spray phase. When
the minitablets reached the proper temperature, all the coating dispersion was sprayed by a dedicated compressed-air-fed gun.
At the same time, the pan speed was adjusted to the ideal value to avoid the cores sticking or being damaged; mixing was ensured
by six shark-fin-type mixing baffles placed in the center of the drum.
Table II: Optimized process parameters for formula A.
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During the process, drying was ensured by a special paddle system blowing the correct amount of inlet air at the desired temperature
and humidity. Cores were dried from the surface and from the bottom, improving the uniformity of evaporation.
Table III: Optimized process parameters for formula B.
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When all the coating dispersion was sprayed, a drying step was performed to reduce the humidity of the cores, then the minitablets
were unloaded manually after a short cooling phase. Optimized process parameters for formula A and B are described in Table
II and III, respectively.
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