Grinding of API in Oral Solid Dosage Process

In the production process of oral solid dosage forms, bulk drug crushing is often an extremely critical unit operation. On the one hand, the particle size of the API may affect drug absorption. For poorly soluble oral solid preparations, the smaller the particle size of the raw material, the faster the dissolution, and the bioavailability of the drug may also be improved. In addition, the particle size of the API has an important impact on the fluidity of the powder, the mixing process and the stratification of the powder, and these factors have an important impact on the stability of the production process.

In the synthesis process, raw materials for oral solid dosage forms are often obtained by crystallization. By controlling the crystallization process, the particle size of the raw material drug can be controlled to a certain extent. However, in many cases, the particle size and particle size distribution of the API obtained by crystallization often cannot meet the needs of the preparation. Therefore, it is necessary to further process the API during preparation production, that is, crush the API to control the particle size within the target range.

Generally speaking, grinding methods can be divided into dry and wet methods according to the different media dispersed during grinding. The wet method is to disperse the API in a liquid medium for pulverization, while the dry method is to pulverize the API in a gas (air, nitrogen, etc.). The dry method is mostly used for crushing raw materials of solid preparations.

The crushing principle of the hammer mill is mainly to continuously beat the raw drug particles through high-speed rotating hammers/hammers, and the particles further collide with the crushing cavity or between particles. These processes can effectively reduce the particle size. When the particle size is small enough to pass through the selected sieve holes, it will be discharged from the crushing chamber. The hammer mill has a large production capacity and low energy consumption, and is more suitable for crushing brittle drugs. Some viscous materials are not prone to particle breakage through mechanical beating and are not suitable for hammer crushing. However, the materials can be cooled to increase the brittleness of the materials and increase the ease of crushing. In addition, hammer crushing generates serious heat, so attention must be paid to the stability of the material. Compounds with a melting point lower than 100°C are not suitable for mechanical crushing methods such as hammer crushing. Hammer mills are generally suitable for crushing particle sizes above 10 μm. Factors related to the crushing effect of the hammer mill generally include the shape and installation method of the hammer blade, rotation speed and feed speed, etc.

Spiral jet pulverizer is a relatively common airflow pulverizer with relatively simple mechanical structure and crushing operation. The pressurized air flow brings the materials into the crushing chamber at a certain speed through the feeding nozzle. There are several nozzles on the same plane around the annular crushing chamber, which spray airflow with a speed of up to 300~500 meters/second into the crushing chamber, forming a vortex airflow, causing the particles entering the crushing chamber to move at high speed with the airflow, and the particles and other particles or the crushing chamber The body was shattered by violent collision and friction. The crushing process mainly involves the collision between particles, followed by the collision between particles and the crushing cavity. The circular motion of particles in the airflow will generate a certain centrifugal force. As the crushing progresses, the particle size and mass decrease, and the centrifugal force received becomes smaller and smaller. When the centrifugal force is small enough, the airflow discharged from the crushing chamber will bring the particles to the center of the vortex airflow, and then be discharged from the crushing chamber with the airflow to complete the crushing process. This vortex airflow allows the crushing and classification processes to be carried out simultaneously, which is beneficial to obtaining a final product with a narrower particle size distribution.