Making the Case for Continuous Processing

Other industries show what is possible in pharma, aided by open control systems.

By Bren Kindelsperger and Delmar Schmidt

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Pharmaceutical manufacturers are using continuous processing but have not been quick to convert from batch to continuous processing, due to concerns about the difficulty and risk of process change. But the basic processes that are used in pharmaceutical manufacturing, such as wet mass granulation, encapsulation, powder wetting, and addition of multiple ingredients have been run on a continuous basis for many years in the food and chemical industries.

This article will explore some of those proven methodologies for continuous processing that may be the basis for many of the existing pharmaceutical manufacturing processes.

It’s Been Done
The types of processes used to manufacture a typical product, regardless of exact formulation, may involve some or all of the following processes or operations:

  1. Addition of some type of fluid to a base (wetting)
  2. Microscopic homogenization of an ingredient throughout the base (dispersion)
  3. Completing the reaction of the active drug with the base to achieve the intended result         (reaction)   

Instead of examining the entire process, break it down to its individual operations, then ask: Have any of the operations been conducted on a continuous basis, and if so, what knowledge could be gained from that experience? In this brief summary, we attempt to do that for the hypothetical process above.

Wetting: There are many applications in operation of simple continuous wetting of powders. The liquid content of these powders can range from a few weight percent to as much as 50 weight percent. Production rates range from kg/hour to hundreds of kgs/hour. Although it is used primarily in the food industry, many chemical and specialty industries also use this process.

Dispersion: The combining capability of continuous processing extends to as high as 99 to 1 (% base to % active addition) with complete dispersion and repeatable results. This is also being accomplished at multiple levels of throughput rates and under a wide range of viscosities. The products involved cut across a wide spectrum of food and chemical applications.

Reactions: In the continuous process, it is possible to utilize the shearing intensity of continuous mixing to conduct reactions within the process and still maintain high through put rates. This is possible because of the tradeoff between time for intensity—in this case, one applies high shear to a small amount of product for a short period of time. This is the opposite of long cycle times of large batch processes, and has been done successfully in many food and chemical applications for decades, as shown in the Table 1.

Shearing/Kneading/Heating Medical/surgical, adhesive, nicotine patch, chocolate conching, cocoa dutching
Shearing/Kneading/Cooling Sorbitol, lethicin medication, Schaffer’s salt, hot breaking of vegetables
Reactions Herbicides, pigments, sodium benzoate, cellulosic ethanol
Wet Mass Granulation Time released blood pressure medication, hormone dispersion, coatings
Grinding Peanut butter pastes and crèmes, microcrystalline cellulose (MCC), chitosan production
Crystallization Vitamin E, sorbitol, by-pass fat
Wetting Carbon black (pacemaker battery paste, motor brushes, magnetic ink), dairy powder (cheese mixing and cooking)
Ingredient Encapsulation Confection flavoring, drug time release, PVOH, Zein solution coatings
Additions of Fillers Composites, wall board, nutrition bars
Homogenization Nutraceuticals

Table 1. Process Steps Successfully Converted to Continuous Processing

Figure 1 illustrates a process that is already being used by many food manufacturers. In this example, materials are fed via feeders, pumps or other conveying method, by electronic control of each piece of equipment and of the process itself, into a single processing unit. The design of the processing unit enables these operations to take place in a continuous method, in order to achieve the same results as in the original manufacturing process, done in separate batch type method. 

Continuous Processing

                                              Figure 1

The general principal of the continuous approach allows the use of a wide variety of equipment to provide continuous, metered feedstock of single or multiple dry ingredients, that are combined with single or multiple liquid type ingredients. The characteristics of the ingredients will dictate the size and type of feeding and pump equipment needed for the application. However, it is possible to obtain equipment that will allow a broad spectrum of ingredient types to be fed, metered, and controlled in the processing unit.

The single processing unit can be configured to provide customized mixing conditions for product specific designs, and highly controlled, consistent results.   

Control System Concerns
One of the major drawbacks when evaluating continuous technology is the difficulty or inability to design both a centralized and simplified control system that will accept a multitude of input signals from disparate manufactures of support equipment. Many manufacturers of support devices such as pumps, feeders, and conveyors also provide proprietary electronic control packages for their individual pieces of equipment. Attempting to communicate with all of these “black-boxes” is a significant barrier. This attempt to specialize their product for a distinct market advantage makes system integration much more complex. 

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