Views: 6 Author: Site Editor Publish Time: 2025-03-06 Origin: Site
Dry granulation (roller compaction) is a process that directly compresses powdered materials into granules through mechanical pressure without adding liquid binders or relying on heating and drying. A simple, energy-saving and environmentally friendly granulation method has been gradually promoted in pharmaceutical production, especially for materials that are sensitive to humidity and temperature. Drugs and colors will not migrate and can be produced continuously.
Equipment: The screw feeder pushes the premixed powder evenly to the gap between the rollers through the rotation of the screw to ensure continuous feeding.
Key parameters: The feeding speed must match the roller speed (such as 10-50 rpm) to avoid insufficient feeding or accumulation. If the material is prone to agglomeration, a flow aid (such as 0.1-0.5% silicon dioxide) must be premixed.
Roller: The surface can be plated with carbide (such as tungsten carbide) to improve wear resistance. some rollers are designed with grooves or patterns to enhance material gripping ability. The roller gap adjustment range is 0.1-3 mm, which directly affects the density of the compact.
Compression: The powder undergoes plastic deformation or brittle fracture under high pressure to form a dense compact (density can reach 1.2-1.8 g/cm³). The pressure range is generally 20-100 MPa, and the roller temperature needs to be controlled for thermosensitive drugs (such as <40℃).
Crushing method: Hammer crusher (impact crushing), suitable for brittle materials with sharp particle edges. Roller crusher (shear crushing), suitable for processes with higher requirements for particle roundness, but the equipment cost is higher.
Screening control: The target particle size usually selects a 20-80 mesh screen, and the proportion of fine powder needs to be <15% to avoid tablet stratification.
The roller compaction method requires that the powder material has good compressibility (secondary compression). Secondary compressibility refers to the ability of the powder to form stable particles through secondary compression after the first compression. Generally, the compressibility index (CI) of the material is > 0.8 (such as microcrystalline cellulose and lactose). The compressibility can be improved by adding plastic excipients such as microcrystalline cellulose, pregelatinized starch or by optimizing the particle size distribution. In addition, lubricants are generally required to reduce the adhesion of the material on the pressing wheel.
The scale-up of the dry granulation process must follow the principles of "geometric similarity" and "dynamic similarity" to ensure that the compression behavior and particle characteristics of the small test are consistent with those of large-scale production. Controllable scale-up is achieved through "key parameter scaling".
Q =π×D×W×t×r×N×(60/1000)(kg/h)
D: roller diameter (cm), W: roller width (cm), t: compact (sheet) thickness (cm), r: compact density (g/cm³, measured by small test), N: roller speed (r/min)
Formula meaning: The output Q is proportional to the roller surface area πDW, the compact volume (t×area) and the speed (N).
Maintain constant parameters: compact thickness (t) to avoid density changes caused by compression time differences; roller speed (N) to maintain similar shear rates to prevent material sticking to the roller or excessive heating.
Enlargement adjustment parameters: roller diameter (D) and width (W), increase proportionally to directly increase production capacity.
| Calculation of density of compressed tablets based on bench-scale equipment data |
| D: diameter of the pressing wheel, cm W: width of the pressing wheel, cm t: thickness of the sheet, cm r: density of the sheet, g/cm1: N: speed of the pressing wheel, rmin Q: output, kgh |
| Using the calculated density, calculate the output of a larger machine |  | D: diameter of the large batch roller W: width of the large batch roller t: thickness of the small batch sheet r: calculated sheet density N: speed of the small batch roller |
| Note: Roller compaction output is directly related to powder feed rate | ||
During the process of dry granulation (roller compaction), the density of compressed flakes (thin sheets) is kept consistent. By controlling the relationship between "compression pressure, residence time, and material flux", the density of the compacted product after scale-up is ensured to be consistent with that of the pilot test (density difference <5%).
Principle: The compression density is determined by the pressure applied by the compression wheel per unit width. The pressure is quantified by Pounds per Linear Inch, (PLI) or kN/cm to ensure that the pressure per unit width remains unchanged after scale-up.
Calculation formula:
Steps:
Pilot test measurement: Optimize and record the linear pressure (such as 5-15 kN/cm) to achieve the target density on the pilot test equipment.
Scale-up calculation: If the width of the large production roller is k times that of the pilot test (such as k=3), the total pressure needs to be scaled up to k×the total pressure of the pilot test.
Example: The width of the pilot test roller is 10 cm, the total pressure is 50 kN → linear pressure = 5 kN/cm.
After scale-up, the roller width is 30 cm → the total pressure needs to be increased to 150 kN.
Principle: The rolling line speed (V) is the linear speed of the roller surface, which directly affects the residence time of the material in the high pressure area.
Formula: V=π⋅D⋅N(cm/min)
Implementation steps:
Pilot test parameters: Record the diameter D(small) and the rotation speed N(small) of the pilot test roller, and calculate the linear speed V(small).
Enlargement adjustment: The diameter of the large production roller is D(large), so the speed needs to be adjusted to N(large) = V(small) / (πD(large))
Example:
Small test: D(small) = 10 cm, N(small) = 20 r/min → V(small) = 628.3 cm/min.
After enlargement, D(large) = 30 cm, then N(large) = 628.3/(3.14×30) = 6.67 r/min.
Principle: The compression thickness t is determined by the feeding rate Q and the roller linear speed V:
Q = V⋅W⋅t⋅r (g/min)
Implementation steps:
Pilot test benchmark: Determine the pilot test feeding rate Q, small corresponding compression thickness t.
Scaling adjustment: The width of the large production roller, W(large) = k⋅W(small), needs to adjust the feed rate to: Q(large) = k⋅Q(small)
The feeding system (screw feeder) needs to be scaled up synchronously to ensure that the feed amount matches the increase rate of the roller surface area. When the feed is insufficient, the compact density is low and the particles are loose. When the feed is excessive, the material accumulates and the roller is blocked.
After scaling up, the roller surface area increases, and the lubricant ratio needs to be appropriately increased (such as increasing magnesium stearate from 1% to 1.2-1.5%) to prevent roller sticking.
The surface area of the roller of large equipment is larger, and the friction heat accumulation is more significant. It is necessary to monitor the roller temperature (such as <50℃), and add a cooling system if necessary.
After scaling up, it is necessary to check whether the particle characteristics (particle size distribution, bulk density, fluidity) are consistent with the pilot test, and adjust the crushing and screening parameters if necessary.
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