Manufacturing pharmaceutical syrups with high-shear mixers

Published: 4-Mar-2024

Silverson Machines shares success stories from three customers who manufacture pharmaceutical syrups and suspensions, and showcases how switching to high-shear mixing equipment has benefitted their production processes

Ibuprofen suspension: manufactured faster with better results

A Silverson in-tank high-shear batch mixer, sold to a pharmaceutical company that produces an ibuprofen suspension in sugar syrup, improved both the mixing process and the end product.

The company had been developing this new product with traditional agitators using kaolin — a type of silicate material — to keep the active ingredient in suspension and make it more stable. Ideally, they wanted to remove the kaolin from the formulation and reduce the size of the ibuprofen particles.

This was not possible with the agitator they were using, however, as it did not provide the shear energy needed to accomplish the task. They had been creating a premix of water, ibuprofen, kaolin and an emulsifier that’s commonly used in oral medication.

After a lengthy mixing time, the solution was then incorporated into a sugar syrup that was produced in a separate vessel (using another agitator to dissolve the sugar in warm water).

Heating the water and cooling the sugar syrup before adding it to the ibuprofen mixture further increased the processing time. The company was mixing batches of 150 L but were keen to increase this and remove the kaolin from the formulation.

They knew that their current process and mixing equipment would make this increase very difficult to achieve, so they contacted Silverson. At first, there was a discussion about running some trials with an in-tank batch mixer; it was thought that this would be most suitable for the application.

But, before a trial could be arranged, the company found out that their counterpart in Pakistan had purchased a Silverson mixer and was producing high-quality products with great results.

On this basis, the company immediately purchased the recommended batch mixer. Once the mixer was delivered, the company used it to produce their ibuprofen suspension and the results were significantly better than they had previously achieved with the agitator.

The batch mixer was able to reduce the ibuprofen particles down to 2–5 microns in a much shorter mixing time. What’s more, the sugar solution could be made at ambient temperature, further reducing the processing time and costs.

The manufacturers were able to achieve the stable suspension they were aiming for without the need to add the kaolin.

Successful scale-up from the laboratory to full-scale production

Another company has purchased multiple Silverson mixers for a variety of applications, such as producing generic pharmaceutical suspensions in liquid form as an alternative to pharmaceutical tablets including Claritin and Prozac.

Manufacturing pharmaceutical syrups with high-shear mixers

These are viscous products that pose the challenge of achieving an acceptable dispersion without agglomerates in varying batch sizes and viscosities. The company first contacted Silverson when they were just beginning to test their application and trialled a Silverson laboratory mixer.

At the same time, they were also assessing equipment from another supplier of high-shear mixing equipment. Evidently, the Silverson technology performed better than that of the competitor and the company invested in the laboratory mixer for batch formulation work.

Shortly after that, they returned to trial a Verso, a laboratory scale inline mixer, which they also purchased for their inline formulation work.

As all Silverson equipment is engineered to the same tolerances, once the company had concluded their batch formulation work, it was easy to scale-up the process from the laboratory to 200 L batches for the small-scale production of the suspensions using a BX60 in-tank batch mixer.

Owing to increasing demand, the company returned to scale-up their inline process. This time, they purchased a Silverson Flashmix powder/liquid mixer, which is used on 4000 L batches containing 175 kg of active powder.

The operating temperature can be anywhere from 25–75 °C and, therefore, the viscosity varies widely depending on the suspension being produced and the formulation … but is mostly in the range of 500–10,000 cps.

Not only is the company now using Silverson rather than a competitor for full-scale production, but they also continue to grow their production line using Silverson mixers.

High viscosity syrup made agglomerate-free with high shear

Another major pharmaceutical company has also purchased a Flashmix powder/liquid mixer, this time for the preparation of a viscous heartburn- and indigestion-relief syrup.

The product was being manufactured using mixers that were not equipped to handle the range of difficult powders that needed to be incorporated or the very high viscosity of the end product. As such, the company was struggling to optimise their desired product, even with very long mixing times.

No matter how long the solution was mixed for, the extant equipment could not break down the agglomerates that had formed and unhydrated powder remained.

More time was subsequently required to complete the overall process as the solution needed to be put through a filtration stage to remove the agglomerates.

After this lengthy and additional step, the company was still not happy with the result and wanted a more uniformly mixed/homogenised product that would be consistent batch after batch.

Manufacturing pharmaceutical syrups with high-shear mixers

The company got in touch with Silverson Machines and a trial was arranged with a FMX25 Flashmix powder/liquid mixer.

It was recommended for this application as the difficult powders could be fed from the powder hopper straight into the liquid stream — immediately passing through a rotor/stator work head — to eliminate any agglomerates.

The powders being mixed were a combination of sweeteners, sugar substitutes, preservatives and 10% sodium alginate to thicken and emulsify the product. During the trial, the FMX25 handled the powders and the increasing viscosity well.

Unlike many powder/liquid mixers, which use a vacuum to entrain powders, the Flashmix literally forces powder into the liquid stream.

This not only allows it to disperse and hydrate large volumes of powders, but it also means that it can be used at higher temperatures and with higher viscosity mixes; this facilitates the high-shear mixing of a wide range of applications that were previously not possible.

The mixer was able to produce an agglomerate-free solution in a significantly shorter mixing time and was also able to eliminate the filtration stage. Consistent results were achieved throughout the trials and the company was very happy with the results.

They have now purchased an FMX25 Flashmix to make the syrup in 130-gallon (US) batches. They are currently in the process of testing their other pharmaceutical syrups using the FMX25 to see if they can further increase the quality.

Silverson Machines has an unrivalled knowledge of the particular requirements of pharmaceutical applications and regulatory bodies, with a wealth of knowledge about a range of pharmaceutical applications.

“Standard” Silverson high-shear mixers offer a high level of hygienic construction and, for more advanced requirements, the company offers a wide range of specially designed ultra-hygienic mixers.

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