Analysis of HPMC industrial production process

1. Raw material refining

Raw materials: α-cellulose (wood pulp/cotton linters, polymerization degree ≥800, ash content ≤0.2%)

Pretreatment:

Alkali boiling delignification (NaOH 10-18%, 170℃/6bar, Kappa number <5)

Multi-stage bleaching (ECF process, whiteness ≥88% ISO)

2. Etherification reaction engineering

Alkali activation:

Cellulose impregnation 18-25% NaOH solution, low temperature (-10℃ to 5℃) pre-expansion (crystallinity reduced to ≤40%)

Methylation stage:

Introduce methyl chloride (molar ratio 1:2.5-3.0), 70-90℃/4-6bar reaction for 3-5h (DS control 1.8-2.2)

Hydroxypropylation stage:

Propylene oxide gradient addition (molar ratio 1:0.1-0.3), temperature segmented control (50℃→85℃), MS target 0.15-0.25

3. Post-reaction treatment

Neutralization purification:

Acetic acid adjusts pH to 6.5-7.5 (conductivity <500μS/cm)

Membrane separation and purification:

Tangential flow ultrafiltration (MWCO 50kDa), remove oligomers (GPC monitors Mw distribution PDI <2.3)

Energy-saving drying:

Three-stage spray drying (inlet 180℃→outlet 60℃, moisture ≤5%, in line with USP<731>)

4. Finished product standardization

Particle engineering:

Airflow milling (D50 80-120μm, span <1.8), metal foreign matter control (XRF detection limit <10ppm)

Functional modification:

Surface siliconization (contact angle <30°) or ionic crosslinking (applicable to controlled release preparations)

5. Quality control system

Key CQA:

Degree of substitution (NMR method, USP<202>)

Gel temperature (DSC determination, ±1℃ accuracy)

2% solution viscosity (Brookfield LV, 23℃±0.5℃)

EHS compliance:

Closed-loop solvent recovery (DMSO recovery rate ≥98%), VOCs emission <50mg/Nm³ (GB 31571)

6. Process innovation direction

Continuous reactor (CSTR series connection, yield increased by 15-20%)

Enzyme catalyzed etherification (cellulase pretreatment, energy consumption reduced by 30%)

Digital twin control (PAT technology real-time control of DS/MS)