Nanonization of Active Pharmaceutical Ingredients

The comminution or desagglomeration of Active Pharmaceutical Ingredients (API) is called micronization. Nanonization is a term for reducing particle size to the nanometer range and brings about several advantages. It further increases the surface area of API’s which could result in enhanced solubility and drug bioavailability. Reducing the particle size of an API possessing poor solubility characteristics can lead to higher specific surface area, thereby increasing bioavailability and dissolution rate. Due to the increased bioavailability a lower amount of API is required which in turn leads to a more cost-efficient product with less risks and side effects for the patient.

NETZSCH is an international, successful family-owned German company. The Business Unit Grinding & Dispersing offers equipment for all process engineering tasks in the fields mixing, dispersing, deaeration, wet- and dry grinding and classifying.

Based on comprehensive experience with GMP-conform production of pharmaceutical products all sizes of NETZSCH machines ranging from small laboratory- to production-size machines, illustration 1 shows a medium-size laboratory mill, excel by the following specific features:

• All product wetted parts are manufactured and certified according to FDA standards
• Material-, production- and calibration certificates are supplied together with the machine
• Optional Sterilization in Place (SIP)
• All direct and indirect product-wetted surfaces are made of stainless steel
• Optional data recording and formulation management.
• Password protection operator management providing different levels of security
• Laboratory mills can be used with variable grinding chamber sizes
• Variable ZrO2, stainless steel 316 or nylon grinding chamber designs on offer
• Splash-proof machine stand
• Comprehensive testing and qualification documentation including FAT, IOQ, FRS, SDS
• Production of GMP compliant machines in the USA
• Trainings and seminars.

Besides the machine design there are other essential conditions for the successful comminution or dispersion of solids. These are the right formulation of the product suspension as well as the selection of the best grinding media and the optimal operating parameters of the mill.

The development of the formulation and the optimisation of the operating parameters can be conducted in laboratory mills. In particular when it comes to the selection of the operating parameters of the mill NETZSCH-Feinmahltechnik GmbH can revert to a pool of experience of more than 6 decades. Illustration 2 shows the development of the particles size distribution of APIs during a grinding test on a laboratory bead mill. The customer aimed at a close particle size distribution with x99,3 < 400>

Once the operating parameters have been optimised the results can be transferred to production-size mills. An essential parameter for the scale-up is the specific energy input, which states the energy input with reference to the product quantity produced. Illustration 3 shows the results of the scale-up from a laboratory agitator bead mill to a production-size mill.

The illustration clearly shows that the results of the laboratory test can be exactly transferred to the production-size plant.

-- Issue 18 --