Segregation Challenges in Pharmaceutical Manufacturing

by: August Jorgensen and Brandon Johnson

The pharma industry is one of the largest growing markets due to advances in biotechnologies and market shifts from Covid-19. Unfortunately, it is also one of the most challenging industries to design equipment for because of the sanitary requirements, government regulations, material/ingredient properties, (and hard-to-pronounce words). The food industry can be a good starting point with some similarities in hygienic design and regulations. Still, the material characteristic difficulties are unique, causing segregation challenges in pharmaceutical manufacturing that cannot be overlooked.

Industrial plants can often be dirty with carbon black in every nook and cranny (at no fault to the plant – carbon is messy!) On the other hand, food plants can be enjoyable to walk into with a cleaner environment. Often, there is an aroma of sweets or familiar foods. While you can get away with unsanitary environments in industrial plants, or the sights and aromatic smells in food plants, this would be unacceptable in the pharma industry due to the potency of ingredients. If you walk into a pharma plant and see any indication of by-products on the ground or smell the aroma of an ingredient, you could be at risk of ingesting harmful levels of potent ingredients.

Pharmaceuticals Ingredients

There are many unique ingredients and common ingredients in the Pharmaceutical Industry (Pharma Manufacturing).

Active Pharmaceutical Ingredients (API)
An example of an API is acetylsalicylic acid, commonly found in aspirin. Or Atorvastatin Calcium, which can be found in Lipitor. These powders are critical to the end product i.e., medication, that a person needs.

A correctly designed pneumatic conveying system is crucial to handling these ingredients. Whether it’s a hospital or dietary supplement company, if they’re making their products with the right ingredients and handling system then consumers will have no problem using them. Pneumatic conveying systems are crucial for transporting materials in an efficient manner which leads to better quality end products. 

If a material handling system is not designed correctly, then the breakdown or contamination of the product can cause damaging repercussions.

In many of the medications consumers take, fillers or binders are added to the API to help round out the medication. These fillers are called Excipients. Designing a well-functioning, efficient system to handle these excipients is just as critical, or even more critical, than handling the API. 

An example of an excipient is Sorbitol, which is found in antibiotics another is Starch found in pain-reliever over-the-counter medications. Corn, Sodium Starch Glycolate, Pregelatinized (cooked and dried), Cellulose, Hydroxypropyl (water and organic solubility), Microcrystalline, Calcium carbonate, Candelilla wax, Croscarmellose sodium, NF, lactose monohydrate, magnesium stearate, microcrystalline cellulose, Colloidal Anhydrous Silica, Gelatin, Titanium Dioxide, Lactose are also common powders. These excipients and others are found in many of the common medications used by American consumers.

The consequences of a material handling system that is not designed correctly can be devastating. From the loss of product and time to potential injury or even death – it’s important that these systems are precisely designed with safety in mind from day one!

Sorbitol is a Carbohydrate (sugar alcohol) that behaves very similarly to sugar. HaF Equipment has installed many sugar handling systems. They are tricky. A few of the challenges is that Sorbitol is Hygroscopic, Combustible, and is Poor-flowing! Every surface, every hopper, every transfer point needs to be reviewed and designed with expert precision.

Cellulose is a common excipient. It is 0dorless, white, and fibrous. The fibrous structure of cellulose particles and the fact that cellulose is very fine and light causes many challenges when trying to transfer cellulose and ensure you don’t have a dust cloud in your plant!

Using pressurized air to move cellulose only packs the particles tighter and tends to plug. Also, when a plug forms, the backpressure in the system increases, and the chances of a dust cloud increase. Not good. The alternative is a vacuum convey system. Instead of packing the particles together, a vacuum system pulls them apart and allows them to flow. And guess what, with a vacuum system, if there are any leaks in the piping system, air leaks INTO the system, instead of cellulose blowing OUT OF the system.

Titanium Dioxide 
A very difficult to handle excipient is Titanium Dioxide. TiO2 is used in pharmaceuticals as a pigment. It is also used in most sunscreens, like zinc oxide. Although this powder is a common ingredient in medication, it is difficult to handle. Titanium Dioxide is easy to compact because it has adhesive-like properties. The result is that when TiO2 is stored in a vessel, it can bridge (meaning it does free flow out of the vessel discharge point), rathole (meaning it sticks to the sidewalls of a vessel and the whole middle column empties while the other material stays in the vessel), and segregate (meaning various particle sizes separate inside a hopper). Great care is needed when handling TiO2. 

Common Segregation Challenges

When handling ingredients, every powder and liquid has unique properties; bulk density, particle shape, particle size, aeration capacity, etc., all impact how the powder behaves.

Segregation of particles in a system can cause many challenges from plugging in the hopper, buildup, and inconsistent batch integrity. There are several ways that segregation can occur.

When the powder enters a storage hopper, segregation can occur as fine powders accumulate at the top. The powder particles are fluidized, and the lighter materials float to the top. The storage hopper is now full of a non-homogenous mixture of powder particles. 

Fine particles have lower permeability than coarse and retain air longer. This is common for mixtures below 100µm in size, making them more difficult to vent or filter out when high rates are used (as opposed to low). 

Dusting (Segregation)
Dusting is an example of particle entrapment. The dusting process occurs when larger particles separate from a mixture because of their slower settling speed and is seen more often with mixes below 50microns.

Sifting (Segregation)
Sifting Segregation is the sifting phenomena that causes segregation to occur in a lateral, or side-to-side motion. When this happens, fines (lighter materials) collect in the center under the point of impact, coarse particles roll off the pile and locate on the sides. Small particles move through a matrix of larger ones, and then segregation occurs. It happens when the difference in particle size is greater than 2:1, and the large average particle size is greater than 500µm and free-flowing.  

The Challenge of Degradation

A spray-dried powder or a delicate powder structure needs to be handled gently. Yet, it can be a challenge because the system has to be gentle while transferring the necessary API or excipient powder from one part of the plant to the other and do it fast enough to keep up production rates! So, how is this done?

The key is to handle the powder at low velocities. It is possible to use compressed air and move the powder very slowly. Dense Phase Pneumatic Conveying technology is one of the best and most efficient ways.


With the growing demand for pharmaceutical manufacturing, precise material handling is more important than ever. HaF’s material handling equipment for pharmaceuticals is engineered to handle your pharmaceutical powders and materials with precision and accuracy. With our equipment, you’ll be able to optimize your production process and ensure that you’re meeting the high standards of the pharmaceutical industry.

CONTACT US today to discuss your pharmaceutical manufacturing equipment needs. 


About HaF Equipment

HaF is a Minnesota-based company with employees spread out across the USA and capabilities world-wide. We’re ready to support your manufacturing industry needs no matter where you live or what type of industry – we’ve got our finger on the pulse Ready to Connect. 

For more information about how we can help you meet your goals, don’t hesitate to call us at (651) 653-5098, or complete the Contact Form on our website.