Material Overview

Peptide drugs, as an important branch of biopharmaceuticals, have a global market size of over 40 billion US dollars. The production of its formulation requires high requirements for the mixing process: content uniformity (RSD ≤ 3%), activity retention rate (≥ 95%), and metal ion control (≤ 0.5ppm). The square cone mixer has become the first choice mixing equipment for peptide freeze-dried powder injections, liposomes and other formulations through three-dimensional spatial motion and shear free mixing principle, with a coverage rate of over 70% in innovative pharmaceutical companies.

Equipment structure

-Square cone hopper: made of 316L ultra-low carbon stainless steel, with electrolytic polishing of the inner wall (Ra ≤ 0.3 μ m), and 8 edges and corners using R30 transition arcs

-Drive system: dual support structure of driving shaft and driven shaft, cycloidal pinwheel reducer (0.5-15rpm stepless speed regulation)

-Sealing device: Triple sealing design (silicone rubber sealing ring+PTFE liner+mechanical seal), leakage rate ≤ 1 × 10 ⁻⁶ Pa · m ³/s

-Online monitoring: Integrated NIR probe (wavelength 1200-2400nm) and temperature and humidity sensor (accuracy ± 0.5 ℃)

working principle

1. Movement trajectory: The hopper undergoes translational rotation in three-dimensional space, and the material undergoes three types of movements simultaneously: diffusion, convection, and shear

2. Mixing mechanism:

-Lifting stage: The material rises along the bucket wall to the critical angle (35 ° -45 °)

-Waterfall stage: Materials scatter along a parabolic path under the action of gravity

-Turbulence stage: mutual permeation and fusion of different component materials

3. Motion parameters:

-Turning radius: 0.8-1.2m

-Revolution speed: 5-12rpm

-Rotation/revolution ratio: 1.5-2.5:1

Advantage features: Three dimensional motion enables full area mixing of materials without mechanical stirring, reducing peptide particle breakage rate by 80% compared to slot mixers, and increasing activity retention rate to over 97%.

Key technological advantages in peptide formulations

-Content uniformity: Passed the FDA required content uniformity test (AV value ≤ 15), with RSD controlled at 1.5% -2.8%

-Cross contamination prevention and control: using quick release interface and CIP/SIP system, residual amount ≤ 0.01% (meeting the requirements of drug production)

-Temperature sensitivity protection: During the mixing process, the temperature rise of the material should not exceed 2 ℃ to avoid thermal degradation of the polypeptide chain

Comparison of Process Efficiency

Innovative technology application

1. Breakthrough in anti adsorption technology

-Nanocrystallization surface: The inner wall of the hopper is coated with nanoscale zirconia, reducing the surface energy to 25mN/m and decreasing peptide adsorption by 95%

-Micro electric field anti adhesion: Apply a 5-10V micro electric field on the hopper wall to form an electrostatic shielding layer

-Inert gas protection: equipped with a nitrogen replacement system (oxygen content ≤ 0.5%) to prevent peptide oxidation

2. Intelligent control system

-Power curve monitoring: Real time monitoring of motor power changes, automatic determination of mixed endpoints (recognition accuracy ≥ 99%)

-Quality comes from design: Establishing design space based on QbD concept, real-time control of key process parameters (CPP)

-Blockchain traceability: Record the parameters of the entire mixing process, in compliance with FDA data integrity requirements (21 CFR Part 11)

3. Modular design

-Volume series: 50L-2000L, covering the entire range to meet clinical sample to commercial production needs

-Aseptic connection: using ISO 2852 standard quick release clamps to achieve aseptic transfer

-Isolator compatibility: The overall size meets the installation requirements of the isolator and satisfies the production of high activity products

Optimization of process parameters