Micronisation or fine milling is a process to significantly reduce the size of particles by grinding. The link between particle size of key constituents of a pharmaceutical product and its performance is well documented with regards to dissolution, absorption rates and content uniformity. Particle size reduction can generally improve the biopharmaceutical performance and hence support the formulation of active substances with poor water solubility or other unfavourable substance characteristics. Proper matching of active ingredient and excipient particle size is an important factor for various manufacturing steps.

 

Micronized powders are used in different branches of industry e.g. pharmaceutical, nutraceutical and biotech industries. Crystals or particles of about 100 microns to 1000 microns are reduced in size to a range of 1 microns to 100 microns. For certain applications, a narrow particle size distribution is required, which can be achieved by our specific micronization technology. A growing demand for micronized raw materials of pharmaceuticals and excipients can be observed during the last years, be it for overcoming said implications or to modify surface properties.

 

Advantages of particle size reduction

• Increase in the specific surface is an important factor for many interactions with the environment (for
  example, diffusion processes, dispersing)

• Increasing the bioavailability of poorly soluble substances

• Specified particle size distributions and particle shapes can be obtained

• Physical and chemical substance changes (morphology)

• Improvement of dispersion in suspensions

• Favourable dissolution or solubility kinetics are obtained

• Better mouthfeel (particle size less than 40 microns are desired to work around grittiness)

• Improving skin sensation e.g. avoiding the perception of solid particles on the skin (particle size less
  than 70 microns are desired)

• Improve the viscosity, e.g. of creams, gels and lotions

• Improving texture of preparations

 

Impact of Micronization on manufacturing

• The particle size can be adapted to the particle size of other ingredients

• Less issues with content uniformity

• Less segregation during manufacturing and transport

• Shorter blending times due to similar particle sizes

• Homogenous suspensions for granulation or coating

• Less clogging of nozzles due to small and constant particles

• Smaller particles can result in a better “taste”/ ”mouthfeel”

 

Impact on products

• Better absorption in the body due to modified diffusion characteristics

• Constant and reproducible dissolution profiles

• Better content uniformity

• Impact of particles size can be measured during development by micronisation of the products in
  different grades (QbD)

• Less impact of API and ingredients (source, inter-batch variability) during product- and process

• Development due to a constant particle size

 

MCKO is a privately owned GMP certified micronization enterprise with US-FDA approval, German health authority inspection and Japan accreditation and is demonstrating excellence and providing meticulous customer attention when it comes to particle size reductions.

 

The site in Oberrot/ Germany comprises of four separated manufacturing areas, all class D equipped with corresponding airlocks. Micronisation can be performed with nitrogen or oil free compressed air. Temperature of the milling gas is fully controlled. The company works with constant and controlled product feeding and uses dedicated filter sets per product. Particle sizes are controlled by classifier wheels (full scale) and monitored by IPC equipment.

 

Equipment at site in Oberrot

Various different mills are available at MCKO production site in Oberrot, Germany, to provide the best

solution for each product.

 

• Fluidized bed jet mills: CGS 16 and CGS 32

• Spiral jet mills: AS 50, AS 100 and AS 315

• Cutting mill: CM 1000

• Swing mill: LM2-P

• Basket type mill: BM 200 (de-agglomeration)

• Pin mill: PM-3-A

 

MCKO offers processing at lower temperatures in closed systems and air conditioned rooms – depending on product requirements. Micronisation using small scale mills can be performed under full GMP with batch sizes of 10g.. Batch size for full scale mills is about 3 kg to tons. As a matter of course, cleaning validation and verification is performed for each product.

 

Services at MCKO

In addition to the micronization of products MCKO can provide the full spectrum of related and complementing services, such as:

 

• Development service incl. statistical test designs

• Analytical testing

• Particle size using laser diffraction system

• Particle size measurements using microscope

• Sieving analysis for particle size above 100 microns.

• Laser scattering method for particle size below 100 microns.

 

Different methods for evaluation can be used, i.e. the Fraunhofer method. A dry powder module or a

  module for liquids are available.

• Identity testing (e.g. NIR, UV-VIS) and NIR.

• Additional tests by external and qualified labs

• Stability storage according ICH

• Shipment with qualified logistic partners

• Storage of products at ambient temperature, cooled at 2°C – 8°C or freeze conditions

• Assistance in GMP, pharma development and quality management 

• Retention samples are stored for 11 years for any requests.

 

Why MCKO

• MCKO has long term track record and experience in micronisation and employs well trained and well
  versed staff.

• Different milling technologies to provide the best solution

• Scale up options from 10g in development to tons for commercial

• Privately owned company with high degree of flexibility

• Well established in the markets,  serving several big pharma companies

• All services at one site in Oberrot Germany

• High standards in quality and manufacturing (US-FDA, Japan, Germany inspected)

 

Contact:

For all enquiries, please contact our dedicated business development partner: