SOP-style road-map to fix (establish) tablet compression parameters for a new product.

 SOP-style roadmap to fix (establish) tablet compression parameters for a new product.

1) Prep: know your powder/granules

• Material data: PSD (D10/D50/D90), true density, LOD, bulk/tapped density, flow (angle of repose, Carr’s, Hausner), cohesiveness, stickiness risk.

• Blend readiness: lubricant type/level (e.g., Mg stearate 0.5–1.0%), lubrication time (often 2–5 min; too much → soft tablets, poor dissolution).

• Moisture window: set an LOD window that avoids capping/lamination (too dry) and sticking/picking (too wet).

2) Define targets & CQAs

• Tablet weight (±3–5%), hardness/tensile strength, thickness, friability (<1% typical), disintegration, assay/content uniformity, dissolution (Q at time).

• Convert hardness to tensile strength to compare across sizes:
  For flat-faced, round tablets: $\sigma_t = \frac{2F}{\pi D t}$
  where F=breaking force (N), D=diameter (mm), t=thickness (mm).
  Typical IR tablets target 1.5–3.0 MPa tensile strength.

3) Choose tooling & geometry

• Tooling: B/BB/D as per size; cup depth/land to mitigate capping, embossing risk for picking.

• Profiling: deep cup may lower lamination risk but can increase sticking—balance with finish & film coat.

4) Plan your trials (screen then refine)

Start on a development/single-station or compaction simulator if available, then move to the production press.

Primary knobs on the press

• Fill depth / dosing cam → tablet weight.

• Feeder speed/agitation → weight uniformity (avoid segregation).

• Pre-compression force → removes air, shapes the plug (start 10–30% of main).

• Main compression force → integrity (map force vs tensile strength).

• Turret speed (rpm) → dwell time; too fast = capping/weight variability.

• Ejection/Take-off (ejection force, scraper, vacuum) → sticking/picking control.

5) DOE (fast, effective)

Run a fractional DOE to map effects and interactions:

Factor (typical range to start)	Low	High	Notes
Main compression force (kN)	6	16	Adjust by blend; fragile APIs may need less
Pre-compression (% of main)	10%	30%	Helps de-aeration, reduces capping
Turret speed (rpm)	15	40	Aim for dwell ≥ 10–12 ms for brittle systems
Feeder speed (relative)	Low	High	Keep die fill consistent; avoid segregation
Lubrication time (min)	2	5	Watch hardness/dissolution shifts
Blend LOD (%)	Spec low	Spec high	Tighten as needed after screening

Responses (IPC at press): weight, RSD of weight, thickness, hardness, tensile strength, ejection force (if available), defects (capping/lamination/sticking %), friability, disintegration.
Fit models, then pick a design space that meets all CQAs with margin.

6) Build your compaction profile

• Generate tabletability (σₜ vs pressure), compressibility (solid fraction vs pressure), compactibility (σₜ vs solid fraction) plots.

• Choose main force that gives target σₜ with ≥20% safety margin from the “defect onset” region (where capping or lamination begins).

• Set pre-compression to minimize capping while not over-working the blend.

7) Lock provisional set-points & ranges

(Example for a 9–10 mm IR tablet on a rotary press—illustrative)

• Weight set-point: 320 mg (range to keep RSD ≤2%)

• Main force: 10–12 kN (range 8–14 kN) → σₜ ≈ 2.0–2.4 MPa

• Pre-compression: 2–3 kN (≈20% of main)

• Turret speed: 20–30 rpm (ensure dwell ≥10 ms; slow down if capping appears)

• Feeder speed: set to maintain weight control without over-shear

• Ejection/Take-off: confirm smooth ejection (<1 kN if measured); polish tooling, adjust scraper & vacuum

• Blend LOD window: e.g., 1.5–2.5% (product-specific)

8) In-process control strategy (Stage 2 PPQ ready)

• Start-up verification: 10–20 tablets—check weight, thickness, hardness; tweak fill depth & force.

• Routine IPC:

  • Weight every 15–30 min (or X tablets)

  • Hardness & thickness every 30–60 min

  • Visual defects continuously

  • Friability & DT: at start, mid, end (or per batch plan)

• Alarms/adjustments:

  • If weight drifts → adjust fill cam/feeder; check segregation.

  • If hardness low → increase main force slightly or reduce speed; verify LOD/lubrication time.

  • If capping/lamination → increase pre-compression, slow turret, ensure moisture in window, reduce main force peak, check granule size (increase fines slightly).

  • If sticking/picking → ensure LOD at low end, consider punch polish/coat, raise Mg stearate a notch, lower speed, optimize de-dusting.

9) Scale-up notes (pilot → commercial)

• Keep specific compaction force & dwell time comparable (adjust rpm by dwell arc length).

• Match shear history (feeder type/speed).

• Re-verify weight control (die fill dynamics change with wider turrets).

• Re-check CQAs—especially dissolution (thickness/porosity shifts).

10) Document the control ranges (for PV/Annex 15)

Create a one-page Compression Parameter Sheet:

Product/Strength/Tooling

• Die: __ mm; Punch: FF/BCD; Cup depth: __ mm

Set-points (Ranges)

• Weight: __ mg (± __ %)

• Main force: __ kN (– kN)

• Pre-compression: __ kN or __% of main

• Turret speed: __ rpm (– rpm)

• Feeder speed: __ % (qualitative if needed)

• Thickness target: __ mm (range)

• LOD window: – %

• Lubrication time: __ min

IPC & Frequency

• Weight/Hardness/Thickness/Friability/DT with sampling plan

Defect control

• Limits for capping, lamination, sticking; corrective actions

11) Quick troubleshooting cheat-sheet

• Capping/Lamination: increase pre-compression; reduce main force peak; slow rpm; adjust LOD upward slightly; enlarge fines fraction modestly; ensure adequate dwell; check tooling land wear.

• Sticking/Picking: lower LOD; improve punch face finish/coating; increase lubricant slightly; reduce speed; add anti-adherent (e.g., talc, silica) if formulation allows.

• Weight variability: stabilize feeder; reduce rpm; verify blend flow/segregation; re-tune fill cam.

• Excessive ejection force: increase lubricant or optimize type; polish dies; reduce main force slightly.