Ease of powder transfer and mixing both depend on a powder's characteristics and the equipment design. Eddie McGee, technical director at Ajax Equipment explains the basics for optimising these processes
Increasingly potent active pharmaceutical ingredients (APIs), high levels of containment, and the need for sterility and rigorous clean-in-place regimes, make the process of designing materials handling equipment for pharmaceutical manufacture particularly challenging. Moreover, once the equipment is in place, dismantling it to resolve blockages and other problems may be impractical in the short-term and highly disruptive to production timetables. Add these manufacturing issues to the commercial drivers of reducing time-to-market and the high value of the API, and it follows that knowing as much as possible about the material's flow characteristics is important if production problems are to be avoided.
Virtually every pharmaceutical material will be in powder form at some point during manufacture. Typically 'pure' API manufacture will begin with a crystalline material which is then purified and filtered to produce a wet powder, dried and milled to a consistent particle size for the secondary stage of production when the dry powder is bulked up by mixing in preparation for tabletting and vial production, for example.
As the powder moves through the manufacturing process its flow behaviour will often change and not always in ways that are expected. Therefore when designing plant equipment the engineer has to consider subsequent processing by a mixer, dispensing by screw feeder or handling in a conveyor used to transfer the API to the next stage.
A milled or micronised material may have a consistent particle size but show poorer flow properties than the unmilled powder. By knowing the powder's flow characteristics at each production stage, combined with experience of similar materials, the pharmaceutical engineer and solids handling equipment supplier are better able to ensure a consistent and predictable flow of material through the process.
The pharmaceutical engineer and equipment supplier can use a range of powder testing techniques to identify the powder properties that determine bulk flow characteristics. The most important tests are considered to be:
- Bulk Density - this provides the driving force for gravity flow for filling a hopper or screw feeder, for example.
- Wall Friction - this determines the resistance to slip on a contact surface, for any given contact load, for example, the way in which a material slips against a hopper wall, mixer blade and a screw auger flight.
- Shear Strength - the feature that inhibits deformation of the bulk material. This is important when considering how compounds disperse when being mixed. If the combined materials produce a powder that is slightly cohesive, this can be better than a free-flowing material that might de-mix (segregate) at the next processing stage.
The measured values can be used to adopt a quantitative approach to equipment design. For example in hopper design, powder test results are determining factors for establishing the design requirements for mass flow in a hopper and avoiding arching at the outlet. To ensure that a hopper will completely discharge the flow channel must be sufficiently large to destabilise any rathole that may form and the wall angle steep enough to allow the contents to self clear. Inserts may be employed as integral to an original design, or used to modify the flow behaviour in an existing hopper.
For difficulties associated with non-mass flow conical hoppers, inserts can sometimes generate slip at the walls by converting the radial flow to planar type or a complex, but more favourable flow form. Shielding outlets can also provide local areas of reduced pressure in which the material flows more readily and reduces the compacting conditions that lead to blockage formation.
Further powder measurements including tensile and cohesive strength can be used to indicate the nature of particle-to-particle attractive and transverse interference values. These tests are useful for quality or comparative tests, compaction characteristics and for fundamental research into powder behaviour. In addition density/compaction tests can provide an important guide to how a material will gain strength with change of density.
Recent research has shown that a useful overall approach to predicting flow behaviour is to take the measured characteristics of wall friction (Øw) shear strength (ts) bulk density (?b ) and add three further factors: mass flow wall angle (ßc) outlet size (Dcrit) and Hausner ratio (H.R. - The ratio of tapped to loose bulk density; the greater the ratio the more sensitive the powder is to handling and hence, likely to be poorer flowing). Using these factors we can produce a "spider" diagram comprising a series of three concentric circles that are divided by axes for each of the characteristics.
These axes intersect with the smallest diameter circle where that particular characteristic describes "easy flow" with subsequent bigger diameter circles defining "modest" and "poor flow". Two idealised situations can then be presented in figure 1 for an "easy flow" material and figure 2, a "poor flow" one with the in-filled part of the "web" detailing the particular characterisation attributes.
The above methodology was recently applied in a pharmaceutical project concerning the design of an agitated screw feeder. From a powder handling perspective, the approach was to treat the hopper and screw feeder as a single construction from which powder was fed to a jet mill for further processing.
The pharmaceutical manufacturer had commissioned independent testing of a variety of milled and unmilled powders. Wall friction, bridging and bulk density characteristics were secured. These indicated that agitation of the powder produced the best material condition for handling both milled and unmilled powders.
The state-of-the-art volumetric screw feeder was designed with a stepped shaft and variable pitch to pick up material progressively from the full length of the agitated hopper outlet, to provide a consistent feed rate to the mill. The agitator and screw feeder drives are controlled by separate invertors to maximise co-ordination between agitation and screw feed for optimum powder discharge. Using the powder handling analysis data, the equipment supplier was thus able to ensure a reliable and controlled feed from the agitator via the screw to the milling machine, successfully metering pharmaceutical powder out of the feeder at a variable rate of between 20 to 100 kg / hour.
Of course, powder testing assumes there is enough powder available for testing in the first place. As pressure on reducing time-to-market grows, so competition for the small quantities of lab-scale API for clinical trials can often leave little material for powder testing. This may be as little as 5 grams, in which case the engineer is forced to either make a flow prediction based on their experience of processing a similar compound or use a simulant (a material that resmebles the compound) and extrapolate results from the powder tests on this material. Both responses must be considered to minimise risk, however.
In conclusion, powder characterisation can go a long way to reducing the risk of materials handling problems during pharmaceutical manufacture. Flow reliability and process functions like mixing depend on the interplay of the powder's characteristics and the design of the equipment being used. A best practice of securing measured values on the compound coupled with design features built into plant which promote flow means a project can deliver product in the right condition and at the right time.