Powder Filling

The types of filling machines available for filling hard-shell capsules and their operating principles have been the subject of a number of reviews (30,58-63). Four main dosing methods may be identified for powder filling:

Auger Fill Principle

At one time, nearly all capsules were filled by means of semiautomatic equipment wherein the powder is driven into the capsule bodies by a rotating auger, as exemplified by the type 8 machines (Fig. 7). The empty capsule bodies are held in a filling ring, which rotates on a turntable under the powder hopper. The fill of the capsules is primarily

Figure 7 Type 8 semiautomatic capsule-filling machine. (A) "Sandwich" of cap and body rings positioned under rectifier to receive empty capsules. Vacuum is pulled from beneath the rings to separate caps from bodies. (B) Body ring is positioned under foot of powder hopper for filling. (C) After filling the bodies, the cap and body rings are rejoined and positioned in front of pegs. A stop plate is swung down in back of rings to prevent capsule expulsion as the pneumatically driven pegs push the bodies to engage the caps. (D) The plate is swung aside, and the pegs are used to eject the closed capsules.

Figure 7 Type 8 semiautomatic capsule-filling machine. (A) "Sandwich" of cap and body rings positioned under rectifier to receive empty capsules. Vacuum is pulled from beneath the rings to separate caps from bodies. (B) Body ring is positioned under foot of powder hopper for filling. (C) After filling the bodies, the cap and body rings are rejoined and positioned in front of pegs. A stop plate is swung down in back of rings to prevent capsule expulsion as the pneumatically driven pegs push the bodies to engage the caps. (D) The plate is swung aside, and the pegs are used to eject the closed capsules.

volumetric. Because the auger mounted in the hopper rotates at a constant rate, the rate of delivery of powder to the capsules tends to be constant. Consequently, the major control over fill weight is the rate of rotation of the filling ring under the hopper. Faster rates produce lighter fill weights because bodies have a shorter dwell time under the hopper. Ito et al. (64) compared an experimental flat blade auger with an original screw auger and found that the screw auger provided greater fill weight (30-60% greater for a test lactose formulation) and smaller coefficients of weight variation (up to 50% smaller at the two fastest ring speeds). The formulation requirements of this type of machine have been the subject of only a limited number of reports. In general, the flow properties of the powder blend should be adequate to assure a uniform flow rate from the hopper. Glidants may be helpful. Ito et al. also studied the glidant effect of a colloidal silica using a Capsugel type 8 filling machine (64). They found that there was an optimum concentration of colloidal silica for minimum weight variation (approximately 0.5% for lactose capsules; approximately 1% for corn starch capsules). Employing a similar Elanco machine in a multivariate study involving several fillers, Reier et al. found that the presence of 3% talc as a glidant reduces weight variation compared with 0% talc (65). On the basis of a multiple stepwise regression analysis of their data, these investigators came to two important conclusions: (i) Average fill weight was dependent on machine speed, capsule size, and the formulation specific volume, in that order and (ii) weight variation was a function of machine speed, specific volume, flowability, and the presence of glidant, but independent of capsule size.

Lubricants, such as magnesium stearate and stearic acid, are also required. These substances facilitate the passage of the filling ring under the foot of the powder hopper and help prevent the adherence of materials to the auger.

Vibratory Fill Principle

The Osaka machines (Fig. 8) use a vibratory feed mechanism (66,67). The capsule bodies held in a rotating turntable pass under the powder held in a chamber. A perforated resin plate that is connected to a vibrator is positioned at the bottom of the chamber. The powder bed tends to be fluidized by the vibration of the plate; this action assists the flowing of the powder into the capsule bodies through holes in the resin plate (67). Fill weight is controlled by the vibrators and by setting the position of the bodies under the powder feed mechanism. The capsule bodies are supported on pins in holes bored through a disc plate. While they pass under the feed area, the pins may be set to drop the bodies to below the level of the disc, thereby causing overfill. However, the capsules are eventually pushed up so that their upper edges become level with the surface of the disc plate. When this occurs, the excess powder is forced out and eventually scraped off. This process affords some light compression of the powder against the resin plates and offers the opportunity to modify the fill weight. Weight variation has been related to the formulation flow properties. Kurihara and Ichikawa reported that the fill weight variation with model

Figure 8 Osaka model R-18O automatic capsule-filling machine. Courtesy of Sharpley-Stokes Division, Pennwalt Corp. Warminster, Pennsylvania, U.S.

OCF-120 was more closely related to the minimum orifice diameter than to the angle of repose (66). Apparently, the minimum orifice diameter is a better analogy of the flowing of powder into capsule bodies than the static angle of repose. No systematic studies of the formulation requirements for this machine have been reported; however, typical stearate lubricants may be indicated to prevent the binding of push rods and guides.

Piston-Tamp Principle

Most capsules are filled on piston-tamp machines. These are fully automatic fillers in which pistons or tamping pins lightly compress the individual doses of powders into plugs (sometimes referred to as "slugs"), and eject the plugs into empty capsule bodies. The compression forces are low, often in the range of 50 to 150 N, or about 50- to 100-fold less than typical tablet compression forces. Hence, plugs are very soft compacts that often are not able to be recovered intact from the filled capsules.

There are two types of piston-tamp fillers: dosator machines and dosing-disc machines. In a survey of equipment used by pharmaceutical companies, Heda found that dosator machines are used in production slightly more frequently than dosing-disc machines (68). Interestingly, about 18% of the companies responding to the survey reported that they use both types of filling machines.

Dosing-disc machines This type of machine is exemplified by the Bosch GKF models (formerly Hofliger-Karg) and the Harro-Hofliger KFM models, among others (Fig. 9).

Figure 9 Hofliger Karg model GKF 1500 automatic capsule-filling machine. Source: Courtesy of Robert Bosch Corp., Packaging Machinery Division, South Plainfield, New Jersey, U.S.

Bosch Dosing Disc Principle
Figure 10 Illustration of the dosing-disc filling principle: (A) view looking down on the dosing disc; (B) side view (projected) showing progressive plug formation. Note the placement of strain gauges on the piston to measure tamping and plug ejection forces (see text). Source: From Ref. 70.

The dosing-disc-filling principle has been described (69,70) and is illustrated in Figure 10. The dosing disc, which forms the base of the dosing or filling chamber, has a number of holes bored through it. A solid brass "stop" plate slides along the bottom of the dosing disc to close off these holes, thus forming openings similar to the die cavities of a tablet press. The powder is maintained at a relatively constant level over the dosing disc. Five sets of tamping pins (e.g., Bosch GKF machines) compress the powder into the cavities to form plugs. The cavities are indexed under each of the five sets of tamping pins so that each plug is compressed five times per cycle. After the five tamps, any excess powder is scraped off as the dosing-disc indexes to position the plugs over empty capsule bodies where they are ejected by transfer pins. The dose is controlled by the thickness of the dosing disc (i.e., cavity depth), the powder bed depth, and the tamping pressure. The flow of powder from the hopper to the disc is auger assisted. A capacitance probe senses the powder level and activates an auger feed if the level falls to below the preset level. The powder is distributed over the dosing disc by the centrifugal action of the indexing rotation of the disc. Baffles are provided to help maintain a uniform powder level. However, working with a GKF model 330, Shah et al. (70) noted that a uniform powder bed height was not maintained at the first tamping station because of its nearness to the scrape-off device.

Kurihara and Ichikawa reported that variation in fill weight was closely related to the angle of repose of the formulation; however, a minimum point appeared in the plots of the angle of repose versus coefficient of variation of filling weight (66). Apparently, at higher angles of repose, the powders did not have sufficient mobility to distribute well under the acceleration of the intermittent indexing motion. At lower angles of repose, the powder was apparently too fluid to maintain a uniform bed. However, these investigators did not appear to make use of powder compression through tamping, and this complicates the interpretation of their results.

In a more recent study running model formulations having different flow properties on a GKF 400 machine, Heda found that Carr Compressibility Index values (CI%) should be 18<CI%<30 to maintain low weight variation (68). Poorly flowing powders (CI% > 30) were observed to dam up around the ejection station. The Carr Compressibility Index is calculated from the loose and tapped bulk density as follows (71):

^Tapped where pTapped and pLoose are the tapped and loose bulk densities, respectively. Higher values indicate that the interparticulate cohesive and frictional interactions that interfere with powder flow are relatively more important. Thus flowability is inversely related to the CI% value.

Dosing disc machines generally require that formulations be adequately lubricated, for example, by adding magnesium stearate, to prevent powder from adhering to tamping pin faces and other metal surfaces, and to reduce friction between any sliding components with which the powder may come into contact. Some degree of compactibility is also important as coherent plugs appear to be desirable for clean, efficient transfer at ejection. However, there may be less of a dependence on formulation compactibility than that exists for dosator machines (61,68).

Harro-Hofliger produces a machine that is similar to Bosch GKF machines, except that it employs only three tamping stations. However, at each station, the powder in the dosing cavities is tamped twice before rotating a quarter turn to the next station. Another difference is that the powder in the filling chamber is constantly agitated to help in the maintenance of a uniform powder bed depth.

Dosator machines The dosator machines are exemplified by the Zanasi and MG2 machines pictured in Figures 11 and 12. Figure 13 illustrates the basic dosator principle. The dosator principle has been previously described (72,73). The dosator consists of a cylindrical dosing tube fitted with a moveable piston. The end of the tube is open, and the position of the piston is preset to a particular height to define a volume (again, comparable to a tablet press "die cavity") that would contain the desired dose of powder. In operation, the dosator is plunged down into a powder bed maintained at a constant preset level by agitators and scrapers. The powder bed height is generally greater than the piston height. Thus, as powder enters the open end, it is slightly compressed against the piston [sometimes termed "precompression" (72)]. While the dosator is at its lowest position in the powder bed, the piston is then caused to apply a tamping blow, thus further compressing the powder captured within the dosator. In the next step, the dosator, bearing the plug, is withdrawn from the powder hopper and is moved over to an empty capsule body where the piston is pushed downward to eject the plug. In Macofar machines, a bushing bearing the capsule body is rotated into position under the dosator to receive the ejected plug (74). For a given set of tooling and powder bed height, the setting of the initial piston height in the dosing tube determines the weight of a given formulation filled

Figure 11 Zanasi Matic 90 automatic capsule-filling machine. Source: Courtesy of IMA North America, Inc., Fairfield, Connecticut, U.S.

into the capsules. For a given piston height setting, increasing or decreasing the height of the powder bed into which the dosator dips also can affect the fill weight.

In one of the earliest reports evaluating the Zanasi machine, Stoyle suggests that formulations should have the following characteristics for successful filling (73):

1. Fluidity is important for powder feed from the reservoir to the dipping bed and also to permit efficient closing in of the hole left by the dosator.

2. A degree of compactibility is important to prevent loss of material from the end of the plug during transport to the capsule shell.

3. Lubricity is needed to permit easy and efficient ejection of the plug.

4. Formulations should have a moderate bulk density. It was suggested that low bulk density materials or those that contain entrapped air may not consolidate well, and capping similar to what occurs in tableting may result.

The relationship between formulation flow properties and weight variation on Zanasi machines has been studied. For example, Irwin et al. (75) compared the weight variation of capsules filled on a Zanasi LZ-64 machine with formulations composed of different diluents and lubricants. The formulations had different flow properties, as judged by a recording flowmeter. Generally, it was found that the better the rate of flow, the more uniform the capsule fill weight was. Chowhan and Chow (76) compared the powder consolidation ratio with the coefficient of variation (relative standard deviation) of capsule weight and found a

Figure 12 MG2 Futura automatic capsule-filling machine. Courtesy of MG America, Inc., Fairfield, New Jersey, U.S.

linear relationship for a test formulation containing 5% or 15% drug, 10% starch, 0.5% magnesium stearate, and lactose q.s. The capsules were filled on a Zanasi machine. Powder flow characteristics were inferred from the volume reduction (consolidation), which occurs when a series of loads are applied to the surface of the loosely packed powder bed in cylindrical containers. The powder consolidation ratio was the intercept of the plot of i V - V P

B V Po where V0 is initial powder volume, V the powder volume at a given surface pressure, P the surface pressure, and P0 = 1 kg/cm2. Further work to assess the usefulness and limitations of this approach appears warranted.

The effect of machine variables on fill weight and its uniformity was evaluated by Miyake et al. (77) using a Zanasi Z-25. In general, they found that the filling mechanism was a compaction process. The following relationship was found to apply:

where r is the density ratio, a(i) and b(i) are constants, and Pr the compression ratio = (H - L)/L, where H is powder bed height and L the piston height (within the dosator).

Figure 13 Dosator-filling principle. Source: From Ref. 83.

The quantitative retention of powder within the dosator during transfer from the powder bed to the capsule shell is essential to a successful filling operation. Applying hopper design theory, Jolliffe et al. (78,79) reported that powder retention requires a stable powder arch be formed at the dosator outlet, and this stable arch depends on the angle of wall friction. In general, there is an optimum angle of wall friction for which the compression force needed to ensure a stable arch is a minimum. That angle will be dependent on finish of the inner surface of the dosing tube as well as the properties of the powder. Generally, more freely flowing powders will require larger minimum compressive stresses than less freely flowing powders. But the rougher the surface, the lower the required minimum stress is likely to be. For example, Jolliffe and Newton showed that the rougher of two inner dosing-tube surfaces finishes promoted the formation of a stable arch by different size fractions of lactose by reducing the cohesive strength required within the powder plug for arching (79).

Heda (68) found that the optimum CI% for minimum weight variation for a Zanasi LZ-64 machine was between 25 and 35. Powders with high Carr Index values > 30 produced stronger plugs with lower weight variation. For more freely flowing powders having Carr Index values < 20, higher compression forces may improve powder retention in the dosator tube.

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