GxP-Blog

Criteria for selecting a suitable capsule-filling machine
There are various requirements and selection criteria to consider when choosing suitable technologies and configurations for a capsule-filling machine.

To decide which capsule-filling machine technology is appropriate for a particular application, it is important to put together the right team of operators, engineers and technical project managers so that they can jointly specify the required selection criteria.

The following essential criteria must be included when selecting a suitable technology:
· physical and chemical properties of the product
· product toxicity and microbial specifications for the planned form of administration/application for capsules (containment strategy)
· complexity of the capsule-filling machine (line configuration and individual machine component selection)
· dosing system
· production and operation concept (number of products)

The suitability of the filling technologies is determined largely by the physical and chemical properties of the relevant product (there are different dosing systems for solid or liquid products):
· inside and outside of the capsule-filling machine as well as its product transport systems
· capsule specifications (formats and materials)

The physical and chemical properties of the product are divided into three main areas:
· particles
· bulk
· structure

All three areas interact with each other and influence each other in various ways, as shown in figure 1 below.

Among other things, the electrostatic and mechanical properties of hypromellose capsules (HPMC capsules) and hard gelatin capsules (HGC capsules) vary.

The mechanical properties of hard gelatin capsules depend on their moisture content, as water works as a plasticizer. These capsules should therefore be used only when the relative moisture content is between 30 and 60%.

HPMC capsules, on the other hand, can be used for larger ranges of relative moisture content. They are less vulnerable to electrostatic charging when the moisture content is higher, for example. In any case, it must be borne in mind that HPMC capsules with lower moisture content can be electrostatically charged more frequently than HGC capsules.

To evaluate the behavior of the capsules to be processed during transport in the capsule-filling machine line, you need to know their physicochemical composition. Additional technical approaches can then be applied in the planning phase, such as the use of conductive materials (or their retrofitting or replacement) to combat the risk of electrostatic charging in advance.

The planned form of administration/application of capsules (e.g. as an inhalation product or oral product) indicates the required containment system and containment strategy, which determine the appropriate system design with regard to cleaning and decontamination and any subsequent process steps for hermetically sealing the capsules.

For example, a double-barrier design (capsule-filling machine in containment, closed housing including a pressure level concept between the containment and the environment) with glove ports can be considered, where the operator works in normal cleanroom clothing. Or conventional equipment may be chosen, in which case the operator is clothed entirely in a personal protective equipment (PPE) suit.

The entire line of the capsule-filling machine including all peripheral systems must be considered. These include capsule transport, the capsule checkweigher and capsule bagging at the end of the process chain. The cleaning of the system should also be included in the overall considerations. The longer and more complex the full line of the capsule machine line and the accompanying peripherals (interfaces via pipeline connections), the greater the risk of product dust getting into them from capsules damaged during the process. And the more complex an entire system is, the more difficult the implementation of GMP- and HSE-compliant cleaning of the system will be. These difficulties can be prevented using technical solutions, such as combining various systems and omitting machine configurations (e.g. capsule weight checks integrated in the capsule-filling machine instead of separate external systems).

Dosing systems There are three basic filling systems on the market that can be used for filling capsules with powders: (see figures 2, 3, 4):
· Drum filler
· Dosator
· Tamping pin

These different types of dosing systems are suitable for different applications, as shown in table 1. At a minimum, these criteria should be used as the basis for selecting a suitable dosing system.

Production and operation concept
The production volume, number of products and the planned operating concept (e.g. campaign concept) for the system determine:
· optimal batch sizes based on suitable machine performance and machine technology
· product changeover times, cleaning times, set-up and format change times.

The aforementioned requirements must be taken into account when selecting a capsule-filling machine for launch or production operation.

Other criteria can also be reflected in the costs and should be taken into account:
· prototype character of the capsule-filling machine (percentages new development/standard)
· investment costs

· service and availability of the supplier
· experience with suppliers
· cleaning strategy for the entire system
· delivery time to handover, completion of OQ, validation expenses
· system capacity utilization in operation

These criteria are evaluated using a rating matrix, so that in the end the most appropriate capsule-filling technology can be selected.

Chemgineering looks forward to supporting you in the evaluation of suitable capsule-filling machines and capsule-filling technologies. We offer workshops, review offers and provide support in choosing a supplier.

We offer a comprehensive range of services from conceptual planning, basic planning and detailed planning to commissioning and transitioning your capsule-filling line into production. Moreover, we will be pleased to support you in the individual phases of qualification required for clean room production in compliance with the regulatory provisions.

¹ Carr’s index = Carr’s Compressibility Index, Indicator for powder compaction