Industries & Machines

Particle Design

Summary

Composing or coating of particles by dry processing using mechanical energy is used to increasing the performance and quality of pharmaceuticals. Dry coating different particles (API; pharmaceutical agents or diluting agent) with various fine particles, polymers, and waxes and API increases dissolution rate, amorphizes medical agents, controls tablet hardness, and enables carrier particle surface modification of inhalation agents. Compared to wet processing, dry processing is simpler and lower cost due to not needing solvents and short processing times.

Examples for pharmaceutical use

Bitterness masking using Mechanofusion (multiple coating of API on diluting agent)

An example of processing using acetaminophen as a model drug: The base particle (crystalline cellulose granules), acetaminophen and binder are feed into the Mechanofusion AMS-LAB and composed. Acetaminophen and binder is fed into the machine and composed an additional 2 times resulting in a multi layer composite. Finally, hydrogenated castor oil is coated as a masking agent. The result is shown in Fig.1 showing a particle with a core of crystalline cellulose with a coating of multiple fine particle layers.

Control of dissolution speed and bitterness masking can be achieved with dry processing by optimizing processing conditions and types of waxes used.

Fig.1 SEM of particle surface

Fig.2 SEM images (surface)

Fig.3 Mechanofusion AMS-Lab-GMP in pharma design

Amorphization processing using Nobilta

An example of amorphization of API using dry composing process: A poorly-soluble API, nifedipine is composed with a cellulose derivative. Fig.2 shows the composite of nifedipine and cellulose derivative after processing in a Nobilta NOB-130.

The nifedipine is dispersed and coated on the surface of the cellulose derivative by the processing. As the processing proceeds, the coating becomes more even. During this processing, there is very little change to the particle size.

Amorphization process

Analyzing the processed material with an X-ray Diffraction (XRD) Instrument, material processed for 1 minute had a lower amount of crystals in the API compared to material that was just mixed. This shows that amorphization has already started. Material processed for 30 minutes shows no peaks indicating crystals, showing that almost all the crystals have been amorphized.

Dissolution Speed

The dissolution speed is the same between raw nifedipine and physically mixed material. On the other hand, the dissolution speed of the composite particles is improved.