Figure 3: Capsule filler for the minitablets dosing group (IMA, Ozzano, Italy). (FIGURE COURTESY OF THE AUTHOR)
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Filling of hard gelatine capsules.
The coated minitablets were then filled (n = 42) into size 0 hard gelatine capsules using a Zanasi Lab capsule filler (IMA
Ozzano, Italy), which has a maximum speed of 12000 capsules/h, equipped with a minitablets dosing group (Figure 3). The dosing
group is composed of a minitablets hopper, a special wheel with a predefined number of holes (the dimensions of which are
dictated by the size of the minitablets) and a drum with pushers for the discharge of the minitablets in the capsule body.
The minitablets enter into the wheel's holes by means of vacuum. The wheel rotates, the vacuum is cut off and the minitablets
are dosed into the capsules by gravity fall.
The minitablets dosing unit is equipped with a camera to check that all the holes are filled with minitablets. If one or more
minitablets are missing, the corresponding capsule is rejected.
Characterization.
The minitablets were characterized as follows:
Weight variation.
The weight variation was determined weighing 20 minitablets.
Friability.
The friability of minitablets was determined by introducing 6.5 g of them in a Roche friabilator (Erweka, Düsseldorf, Germany)
at a rotational speed of 25 rpm. After 100 rotations, the minitablets were sieved over a 250 µm sieve. The friability value
was calculated as the percentage of the final weight after sieving to the initial weight of the minitablets.
Crushing strength.
The crushing strength was tested (n=20) using a TBH 200 (Erweka).
Scanning electron microscopy (SEM).
The coating surface and the cross-section slice of minitablets were examined using scanning electron microscopy (ESEM-FEI
QUANTA 200, FEI, Eindhoven, The Netherlands); the samples were previously sputter-coated with gold.
Determination of actual drug content.
The analysis of the drug content was carried out by dissolving 30 mg of minitablets in 100 mL of pH 7.4 buffer. The amount
of drug was then spectrophotometrically determined after 24 h (UV2 Spectrometer, Unicam, Cambridge, UK) at 271.8 nm. Each
sample was analyzed at least in triplicate.
In vitro drug release profiles.
In vitro dissolution tests were performed using the USP Apparatus 2 (paddle) (Pharmatest, Steinheim, Germany) rotating at 50 rpm.
As a dissolution media, 900 ml of pH 7.4 phosphate buffer was used at a temperature of 37 ± 0.5 °C. Samples of uncoated and
coated minitablets containing an amount of drug chosen to assure sink conditions (C < 0.2 Cs) were added to the dissolution
medium. The solution was filtered and continuously pumped to a flow cell in a spectrometer (UV2 Spectrometer, Unicam, Cambridge,
UK) The amount of drug dissolved was analyzed at 271.8 nm. The dissolution tests were performed at least in triplicate.
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