Technologies

Handling hazardous processes safely is an integral part of Dipharma’s culture since our beginning, in 1949, as a civil explosives manufacturer. A constant theme for our business has been building a culture to handle dangerous chemicals and perform hazardous processes in a safe manner.
This extensive experience has shaped our ability to safely carry out complex and hazardous reactions used in the production of APIs, while also in compliance with cGMP protocols and meeting customers’ quality expectations.
The implemented technologies, the culture of safety and the experience in managing reactions couldn’t have been achieved without our talented employees.
The support we provide to our customers, in both our generic and custom synthesis businesses, is the result of having put those skills in capable hands.

We put emphasis on the strategic cooperation with our sister company Biazzi SA, the engineering company that leads the market in the development and optimization of niche technologies, special equipment and high-performance manufacturing complexes throughout the world, including many tailor-made continuous production sites.
Biazzi SA is the reference company for explosives, nitration and hydrogenation, hence it is a perfect partner for Dipharma’s technological growth.

In terms of complex reactions and processes, our portfolio includes:

Hydrogenation is a widely used technology, but only a few companies are able to offer a fully cGMP-compliant hydrogenation plant.
Dipharma has historically adopted industry leading Biazzi hydrogenation equipment, for highly efficient patented technology that delivers low impurity levels.

Both our pilot and industrial hydrogenators are able to perform reactions at a pressure up to 40 bar and at a temperature up to 220°C. All parts of the equipment have been properly designed, positioned and maintained in accordance with cGMP.

Our capabilities include:

  • High pressure hydrogenation up to 40 bar
  • High temperature hydrogenation up to 220°C
  • Heterogeneous hydrogenation
  • Homogeneous hydrogenation
  • Reductive amination
  • Catalyst expertise (Ni, Pd, Pt, Rh, Ru…)

Dipharma’s first technological expertise was on nitration processes. Although today nitration reactions are widely used at lab scale, the potentially explosive nature of these reactions increases the complexity of managing the reaction, particularly during the scale-up. We bring differentiation, with our unique expertise derived from the explosives industry and explosive production technology design. This background provides us with a special insight into the best ways to manage the risks of nitration reactions, so we end up with a safe process, whether in a batch or continuous environment.

Our long-lasting strategic partnership with Biazzi SA, a world leader in nitration technologies, our extensive skill and experience in process design, and our in-house facilities for process’ safety testing, are the pieces of the puzzle where Dipharma is the ideal partner to develop your nitration process.
We have a strong track record in batch and continuous processes for the synthesis of:

•  NITRO AROMATICS
•  NITROHETEROCYCLES

Whatever your nitration requirements, we’ll study them and develop the best way to perform them safely and efficiently.

Nitroesters are molecules with a high-energy content which can decompose and become explosive if not handled appropriately.  We have a deep knowledge of nitroesters’ safe production, mixing, storage, transportation and regulation of explosives.
Dipharma frequently utilizes continuous process manufacturing of nitroesters, like the one originally developed to make nitroglycerine, so to minimize the inherent risks while keeping a high level of productivity.
In addition to the knowledge and the experience in handling explosive compounds, we also offer in-house equipment to measure explosive properties of materials like:

  • Koenen test
  • Fall hammer test
  • Friction test

Azides are very versatile compounds, although inherently-explosive. They can either be active compounds, or further processed towards the synthesis of:

  • TETRAZOLES
  • ISOCYANATES
  • CARBAMATES
  • AMINES
  • ALPHA-AMINOCARBONYLS

A specifically designed plant and the capability to safely handle the process are two key ingredients required for the manufacture and supply of azides as Active Pharmaceutical Ingredients or intermediates. Dipharma can offer production facilities specifically designed for the handling of azide compounds under cGMP conditions, as well as considerable experience in the safe execution of complex azide reactions. We have specifically dedicated a full-cGMP facility for the production of tetrazoles.

Sugars and aza-sugar derivatives are a special niche of products among APIs.
Our strategies to manufacture these compounds has proven to be effective, thanks to establishing protocols that can be easily scaled-up to full industrial scale.

Our industrial skill allows us to safely handle highly reactive compounds like Hexyl-lithium, Grignard reagent, Magnesium diisopropylamide, which can easily promote the formation of reactive intermediates at scale.

In addition to our experience gathered on ton-scale processes, we have mastered cross-coupling reactions, designing the most efficient process and then scaling it up to industrial volume.

Suzuki, Negishi and Sonogashira reactions are widely carried out at all our manufacturing sites; a special focus is put on precious metal scavenge & recovery, so to achieve a competitive process without any compromise on the quality of the final product.

On top of safely carrying out complex and hazardous chemistry, we are able to cover a wide range of synthetic reactions.

Our portfolio of expertise includes:

  • Use of nitroalkanes (Henry reaction)
  • Wolff-Kishner reduction
  • Borane reduction
  • Curtius reaction
  • Hoffman reaction
  • Hydrogen peroxide oxidation
  • Epichlorohydrine chemistry
  • Dissolved-metals reduction
  • Synthesis of enantio-pure compounds:
    – Asymmetric synthesis
    – Optical resolutions
  • Enzymatic Chemistry

Dipharma’s manufacturing sites and people are also skilled and equipped for the handling of hazardous raw materials such as chlorine, hydrazine hydrate, gaseous ammonia, hydrogen peroxide, sodium, dimethylsulphate and nitroalkanes.