Siegfried has vast experience with reactions from the following classes including scale-up of those reactions to commercial quantities:

Looking for something else? We can make it happen!

We would be pleased to answer all your questions regarding these and other types of reactions. 

Siegfried offers a broad spectrum of technologies for the development and manufacture of solid dosage forms, ranging from rapid-release tablets to controlled-release formulations.

Based on more than 30 years of experience and application with an extensive range and type of products, our customers gain more knowledge, Innovation and technological expertise through the following services: 

• API characterization
• Excipients compatibility
• Pre-formulation for early safety studies 
• Small scale formulation work
• Packaging screening for up-front stability
• Up-front stability testing
• Development and validation of analytical methods 
• Validation of manufacturing process according to cGMP
• Process optimization
• Production and release of clinical trial material (CTM)
• Stability testing (ICH)
• Compilation of source documents for registration
• Regulatory support and advanced services
• Scale-up and technology transfer to the commercial site

Our state-of-the-art equipment and development department offers a wide range of the following technologies:

• Powder blending
• Wet granulation with high shear mixer
• Fluid bed spray granulation / drying
• Roller compaction
• One-pot granulation
• Pellet extrusion and spheronisation (IR, DR, SR)
• Tablet compression (IR, SR, Oral Disintegrating Tablets, minitablets)
• Coating (granules, pellets, tablets, IR, DR, SF)
• Hard gelatin capsule filling (granules, powder, pellets)

We also offer development of other administration forms (e.g., injection preparations, eye drops, etc.) under non-GMP conditions.

The increasing trend seen for active pharmaceutical ingredients (API) currently under worldwide development is towards ever higher potency levels and pharmacological activity. Such increased compound potency involves, however, associated potential occupational health hazards that require adoption of a range of special containment measures to ensure safe operation through all phases of development and manufacture.

These measures relate to:

• Protection of personnel 
• Protection of product 
• Protection of the environment

For highly potent materials, segregated high containment facilities and production areas are used at Siegfried to control the specific material risks, adopting the following basic principles:

• Siegfried protects its employees from hazards & risk of harm.
• Exposure to harmful chemicals must be avoided.
• Management and employees are well trained to take responsibility for the correct implementation of protective measures. Risk assessment and standard operating procedures about how to handle highly potent materials are established and in place. 
• Technical, engineering and organizational control measures are adopted as the first measure of choice and are augmented with additional measures such as personal protective equipment (PPE) where necessary (risk based approach).

High Containment Facilities and Capabilities

Drug substance (Zofingen and Evionnaz sites, Switzerland)

• Handling of drug substances with OEL down to 1μg/m³
• Modern state-of-art development & analytical building with specific separate controlled areas for synthesis, process & analytical development
• Segregated cGMP production facility for high-potency material process scale-up & API manufacture
• Commercial scale cGMP production facility
• Separate material, waste & personnel workflows 

Drug product (Barberà del Vallès, Spain)

• Completely segregated cGMP production area (550m²) dedicated to high-potency material handling
• Handling of drug substances based on risk assessment with OEL down to 0.1μg/m³
• Complete production train for manufacturing of high-potent products offered:
  • dispension
  • blending
  • granulation
  • roller compactation (under evaluation)
  • fluid bed processing
  • encapsulation
  • tableting
  • pan coating
  • packaging in blisters and bottles 
• Equipment fully contained
• IPC lab to handle highly potent materials implemented
• Analytical processes suitable to perform all kinds of DP testing for high-potent products on-site
• Dedicated high-potent capabilities for blister and bottle packaging; brite stock packaging concept to perform further packaging operations (secondary, tertiary) in standard area
• Operating in external breathing air suits available
• Separate material, waste & personnel workflows

Physical Operations are crucial steps in API Manufacturing which have to be understood and controlled. We at Siegfried understand the importance of physical operation steps like e.g. extraction, distillation, crystallization, filtration or centrifugation and drying technologies. We have implemented dedicated tools, equipment and experimental protocols to investigate and optimize physical operations whenever needed.

The physical properties of an Active Pharmaceutical Ingredient (API), such as flow properties and particle size distribution, are crucial for the success of a drug formulation and its bioavailability. Therefore, we continually invest in the necessary physical operations (from crystallization, filtration and drying technologies to milling, micronization and spray drying) which best tailor an API’s properties to the needs of a formulation. By bridging the gap between bulk API manufacture and drug product formulation, Siegfried provides you with the physical processing capabilities you need and can expect.  

We offer you more through a range of equipment and technical expertise for crystallization, drying and milling, and we further can manipulate an API’s physical properties through spray drying and micronization.

Milling and Micronization
The last operations in the manufacturing of a bulk API are milling and micronization. Here the physical properties are finalized and c-GMP requirements for manufacturing are high. The requirements for defined and robust Particle Size Distribution of APIs have increased with the years. Siegfried provides milling and micronization services and expertise from lab to manufacturing scale. 

Certain prevailing trends in pharmaceutical development are driving the increasing need for micronized API with mean particle sizes below 10 µm. One factor is that APIs are becoming more potent such that a fine and narrow particle size distribution is needed to guarantee e.g. content uniformity of the formulation. Secondly, APIs increasingly have lower solubility, and micronization is needed to increase the surface to volume ratio to increase bioavailability.

To meet this growing market need for micronized API, Siegfried is expanding its Jet Mill capabilities. By using Design of Experiment and Quality by Design approaches, we evaluate robust parameters for micronization and milling to ensure reliable particle size distribution, working with our customers to achieve the desired specification.