Effect of roll compaction pressure on the properties of high drug-loaded piracetam granules and tablets

Figures & data

Table 1. The composition of granules and tablet core.

Ingredients	Composition of
	granules	tablet core
	% (w/w)	% (w/w)	mg/tablet
Piracetam (D50%=115µm)	83.54	80.00	200.0
Kollidon^®30	3.34	3.20	8.0
Avicel^® PH-101	13.12	12.56	31.4
Ac-Di-Sol^®	–	3.20	8.0
Aerosil^® 200 Pharma	–	0.40	1.0
Magnesium stearate	–	0.64	1.6
∑	100.00	100.00	250.0

Figure 1. The schematic illustration of the roll compactor and the main functional parts: (1) vertical forced screw feeder; (2) compaction rolls; (3) rotor sieving mill.

Table 2. Summarized process conditions of granules manufacturing with industrial roll compactor.

Conveying unit
Drum-feeder speed	35 rpm
Feeding and roll compacting unit
Screw feeder	40 rpm
Rolls’ speed	20 rpm
Hydraulic roll compaction pressure	4, 5 or 13 MPa
Total roll compaction force	18.5, 23.2 or 60.3 kN
Milling unit (hammer mill)
Rotor sieving mill	125 rpm
Square aperture size	1.0 mm
Productivity of granulation, Av. (±S.D.)	39(±0.5) kg/h

Table 3. Parameters of the coating process.

Coating process steps	Pan speed	Spray rate	Atomisation pressure	Inlet air volume	Inlet air temperature	Tablet’s temperature
	rpm	g/min	bar	m^3/h	°C	°C
Warming-up	5	0	0	80	60	Up to 42
Coating	16	5–14	1.3	80	60	39–42
Drying	5	0	0	80	60	50
Cooling-down	5	0	0	80	30	Until 35

Figure 2. Light microscopy images of piracetam substance before (A) and after milling (B).

Figure 3. Particle size distribution (A and C) and cumulative weight fractions (B and D) of piracetam substance before and after milling (A and B) and roll compacted granulates (C and D).

Figure 4. DSC profiles of raw, milled and for roll compacted (13 MPa) and then milled piracetam.

Table 4. Endotherm onset and peak temperatures for raw, milled and for roll compacted and then milled piracetam.

Sample of	Onset1, °C		Peak1, °C		Peak2, °C
piracetam	Av.	S.D.	Av.	S.D.	Av.	S.D.
Raw	140.7	0.2	143.7	1.4	159.2	1.6
Milled	126.0	1.4	131.7	1.3	157.8	1.1
Roll compacted and milled formulation	116.4	0.4	122.5	0.1	158.4	0.3

Figure 5. Effect of roll compression pressure on the D_10%, D_50%, and D_90%.

Figure 6. Light microscopy of roll compacted granules, cross-section (after determination of tablets hardness) and the surface of tablets and surface of coated tablets prepared at different roll compaction pressure and tableting at 25 kN.

Figure 7. The effect of tapping on the density of roll compacted granules (RC granules) and the mixture which is intended for the tableting (tablet-mix).

Figure 8. The effect of roll compaction pressure on the mass flow rate (FR) and Hausner ratio (HR) of roll compacted granules and the mixture which is intended for the tableting.

Figure 9. The tablet hardness is a function of (A) roll compaction pressure; (B) tableting speed and; (C) roll compaction pressure and tableting speed.

Figure 10. The effect of medium pH on the drug release from coated piracetam tablets prepared at 4 MPa roll compaction pressure (A). The effect of used roll compaction pressure (4 vs. 13 MPa) on the drug release from coated piracetam tablets at pH 1.2 (B).