We deliver APIs with a tailor-made PSD
We deliver APIs with a tailor-made PSD (Particle Size Distribution) through micronisation and other technologies
Particle size distribution is a key attribute of quality
Polpharma API, US FDA-approved manufacturing plant offers full-service API process development and contract manufacturing, applying all the available technologies required to obtain the preferred particle size distribution.
Particle size distribution (PSD), in addition to polymorphic form, plays a key role in the dissolution and bioavailability of drugs.
Therefore, it is one of the major concerns in the pharma industry. Determining the correct PSD and polymorphic form and then obtaining it repeatedly is becoming one of the most challenging phases of drug product development and manufacturing.
Many technologies are used during API manufacturing processes to achieve the correct PSD: Crystallisation, micronisation, milling or sieving.
The methods chosen depend on the needs.
Solid State Chemistry study for proper understanding of crystallisation
The Solid State Chemistry (SSC) study performed at Polpharma API enables us through a suitable process to understand crystallisation.
During this study, we determine the relationships between process parameters and particle size distribution (or polymorphic forms). The most important part of this study, the design space, often called ‘safe space’ is determined, which includes the ranges of the crystallisation process for which the proper quality is expected.
During this study, the metastable zone (MSZ) of the crystallisation process is also established. The MSZ can be useful to define a correct point of seeding.
In many cases, the use of seeds can help in obtaining the correct distribution of particle size (or the correct polymorphic form) directly from crystallisation. The use of seeds reduces process variability and is a guarantee for the repeatability of the process, contrary to a process without using seed, for which typically much greater variability is observed.
Many systems that we use also support and help to analyse the crystallisation process in real time.
cGMP Pilot Plant for process verification and validation
During the pilot plant, the process is verified and validated in a full cGMP environment at Polpharma API manufacturing plant, and transferred to manufacturing scale, if needed.
A microniser is available at this scale, which helps us in the preparation of a different size of particles for our customers for their first stability tests, bioavailability tests and formulation, and in the end, it helps us to choose the correct and final particle size.
Micronisation, milling or sieving as alternative techniques
As opposed to obtaining the desired PSD directly from crystallisation, other technologies such as micronisation, milling or sieving can also be applied.
Polpharma API cGMP-compliant multipurpose plant offers a full service for all the above techniques. We have a highly qualified team of professionals with many years of experience in particle size reduction technologies.
Depending on the needs, one of the above-mentioned techniques is applied and the process is optimised with the application of statistical methods for the design of experiments, in accordance with the QbD approach, if required.
Finally, the optimal conditions for the above processes are defined in order to guarantee that the desired PSD is obtained ‘for the first timeְ’ and this can be repeated. Such an approach ensures low variability and maximum process efficiency with minimal manufacturing costs. As a consequence, a stabilised process that achieves APIs with a repeatable PSD is achieved.
Micronisation: the key technology for particle size reduction
Polpharma API has two jet-mill micronisers in manufacturing scale and one in pilot plant. They all compliant with cGMP procedures.
The micronisation process facilitates the reduction of the particle size of a substance in powder form down to micrometre size, greatly increasing the exposed product surface. This technique is especially intended for heat-sensitive products, because the temperature remains relatively constant throughout the whole process.
Particle size reduction occurs without the intervention of mechanical components, but a pressurised process gas is used to impart high velocity to particles and cause high energy impacts between particles.
Particle size reduction is obtained through particle collisions inside the micronisation chamber.
Milling and sieving are additional useful techniques
As an alternative to a microniser, various types of mills (pill mills, classifier mills, etc.) that we own are also often considered, especially when very small size of particles obtained through micronisation are not required (above 10 microns).
In many cases, sieves can also be suitable and are especially recommended when a specific fraction with narrow particle size distribution is expected in the end.
Polpharma B2B, your European API supplier
Our professional equipment and qualified team enable us to offer all these techniques at our production site. The equipment eliminates production downtimes owing to possible delays in production or supplies by third parties.
We can provide various molecule sizes for testing your dossiers.
Our knowledge and experience facilitate a smooth scale up.
We offer full Contract Manufacturing services for all the above techniques.
We strive for the integrity of our processes to save time and deliver quality.
Expert in Development and Technology Transfer