Syringe Siliconization Process Investigation and Optimization

Effect of Fixed-Position Spray on Coating Distribution Uniformity

Figure 2a–c shows distribution uniformity results for the fixed-position spray coating at 5, 20, and 35 mm past the flange, respectively. Spraying near the flange (5 mm) resulted in silicone deposition mostly on the flange side of the barrel and leaving the barrel on the needle side uncoated. When the nozzle was deeper into the syringe (20 mm), the middle section of the barrel was coated. Further into the syringe at 35 mm past the flange, coating occurred primarily at the needle side. This finding suggests that fixed-position spray yields uneven distribution and that the nozzle needs to spray and retract simultaneously. Spraying over the range of 5–35 mm past the flange along with nozzle movements may result in uniform coating over the entire barrel. This will be studied using the pilot-scale system and results will be discussed later.

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Figure 2

Glass powder testing on syringes coated with 0.5 mg of silicone oil at three fixed positions, (a) 5 mm, (b) 20 mm, and (c) 35 mm past the flange, using 5 psi air-to-nozzle pressure.

Effect of Spraying Nozzle Position, Nozzle Pressure, and Spray Rates on Coating Amount

The design of this experiment involved the variation of three process parameters—three nozzle spraying positions (10, 27, and 44 mm past the flange), two air-to-nozzle pressures (5 and 15 psi), and three spray rates (0.420, 4.316, and 8.210 mg/s). The selection of these spray rates was intended to cover a wide nozzle movement range, that is, deep dive with slow retraction and shallow dive with quick retraction. A full factorial experimental design set with these variables gives 18 sets of conditions, that is, a total of 180 samples at n = 10. The target dose is 0.3 mg silicone for all conditions.

The results for coated silicone amount (Figure 3) reveal an obvious problem: a significant number of under-coated samples (<0.1 mg), including no coating (zero silicone-coated). It appears that the siliconization bench-top unit occasionally mis-sprayed, or sprayed prematurely. As the nozzle dived in and out of the syringe, it pinched the Teflon tubing between the pump and the nozzle to flex. The flexing movement could squeeze a minute amount of silicone oil out of the nozzle and spray out of the cycle (not inside the syringe). When the tubing returned to a relaxed position, the silicone level retracted and left a void volume at the nozzle tip. Thus, the syringe in the next spraying cycle would be undercoated. The mis-spray problem confounded the data and allowed for few conclusions to be drawn. This problem occurred randomly and needed to be resolved or minimized before other experiments could be performed.

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Figure 3

Result summary of coated silicone amount for syringes coated at three fixed positions (10, 27, and 44 mm past the flange), two air-to-nozzle air pressures (5 and 15 psi), and three spray rates (0.420, 4.316, and 8.210 μL/s) with a target silicone dose of 0.3 mg.

Approaches to Resolve Mis-Spray/Premature Spray Issues due to Tubing Flex

A straightforward approach is to shorten the distance that nozzle travels as well as the length of tubing between the pump and the nozzle. To test this concept, an extension (95 mm) was inserted at the top of the syringe fixture (Figure 1d) to minimize the distance that the nozzle travels (only inside the syringe), and the tubing length was reduced to only loosely hang in the air. This setup was used to spray 0.3 mg of silicone during nozzle retraction over the range of 30 to 10 mm past the flange. Two parameters were varied at three levels, air-to-nozzle pressure (5, 10, and 15 psi) and retraction speed (50, 100, and 150 mm/s). Thus, this study involved nine conditions (n = 10) with a total sample size of 90 syringes.

The silicone amount results in Figure 4 show a great improvement in repeatability of the silicone dose, with only two samples coated with <0.1 mg silicone, including one with zero coating (5 psi/100 mm/s). This suggests that tubing flex was much reduced but not completely eliminated. Overall, the average coated silicone weight is less than the target dose (0.3 mg) for most of the conditions, suggesting that some silicone droplets may be lost to depositing on the nozzle and/or being blown out of the syringe. The effect of the air-to-nozzle pressure and the retraction rate on silicone loss is not clear from this study. Conceptually, faster retraction may result in greater silicone loss (less coating) because the downward movement of the nozzle can offset the upward velocity of the spray so that some droplets may flow with air out of the syringe instead of depositing on the barrel.

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Figure 4

Result summary of coated silicone amount with a modified experimental setup using a syringe extension (95 mm) and a shortest tubing length (∼25 cm). Syringes were coated with a moving nozzle that dived in 40 mm past the flange and sprayed across the range of 30–10 mm past the flange during retraction using three air-to-nozzle pressures (5, 10, and 15 psi) and retraction speeds (50, 100, and 150 mm/s) with a target silicone dose of 0.3 mg.

There are other approaches that may be able to completely eliminate the tubing flex issue. One is to mobilize the nozzle and the pump (including the tubing in between) as one unit. Unfortunately, the linear actuator in the current setup was not capable of carrying the weight of the pump module. However, the pilot-scale siliconization unit had such a feature (Figure 8) and was tested as discussed later.

Another approach is to keep the nozzle stationary but to move the syringe instead. The nozzle still sprays upwards but stays motionless during syringe fixture movement. With both nozzle and pump being motionless, there should be no tubing flex. However, this approach is not within the scope of this investigation and will present a different configuration to the pilot unit to be evaluated later.

Finding Key Process Parameters on Coating Uniformity

As determined earlier, for silicone droplets to be evenly distributed across the whole barrel surface, the spraying nozzle has to dive in the syringe and spray during retraction. Proper siliconization at the needle side of the barrel is important. For spring-based auto-injection devices, the most severe challenge will be at end of the stroke, when the available spring energy will be at its lowest level (11). To reach this area, the nozzle has to dive in the syringe barrel deep enough or spray silicone oil droplets far enough to cover the needle side. The upward velocity of the droplets is dictated by the change in air-to-nozzle pressure but can be offset by nozzle retraction velocity and gravity. Therefore, to evaluate the effect of changing the spraying process on silicone distribution, four process parameters were varied: nozzle retraction rate (50 or 200 mm/s), nozzle spray range (22–10 or 44–10 mm past the flange), air pressure to the nozzle (5 or 15 psi), and target silicone quantity (0.2, 0.5, or 1.0 mg). Please note that nozzle retraction rate is important for production speed. A normal production-speed siliconization spray should be under 1 s per cycle and 50 mm/s is near that mark, depending on dive-in depth. Samples created for this test are listed in Table II with n = 10, where three samples were used for glass powder testing and three for Instron glide force testing. The glide force testing results are also summarized in Table II, where the number of passing samples is listed out of three. Several observations can be drawn from these results.

I. Nozzle Retraction Speed:

Nozzle retraction rate plays an important role for distribution uniformity; the faster the retraction, the less uniform the coating. For example, glass powder testing for syringes coated with 0.2 mg silicone and sprayed in range of 10–44 mm past the flange using 15 psi air-to-nozzle pressure shows less uniform coating at the retraction rate of 50 mm/s (Figure 5a) than 200 mm/s (Figure 5b). Fast downward retraction offsets droplet velocity so that the droplets failed to reach the needle-end of the barrel despite a deep dive. This visual observation was confirmed by the glide force measurement. All three syringes coated at the 50 mm/s retraction rate show a constantly low glide force (<2 N) over the barrel length of 0–38 mm (Figure 5a). At the high retraction rate (200 mm/s) all three syringes display an increasing glide force profile, initially below 2 N (between 0 to 15 mm) and escalating dramatically for the rest of the barrel (Figure 5b), indicating the lack of lubrication on the barrel near the needle.

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Figure 5

Glass powder testing and Instron glide force profile for syringes coated with 0.2 mg silicone and sprayed in range of 10 to 44 mm past the flange using 15 psi air-to-nozzle pressure at the retraction rate of (a) 200 mm/s or (b) 50 mm/s (for the three syringes on the left).

III. Air-to-Nozzle Pressure:

By the law of conservation of energy, higher nozzle pressure can disperse droplets faster and farther. In Figure 6 for glass powder testing, despite the significant pressure difference, silicone coating is only marginally deeper using 15 psi air-to-nozzle pressure (three syringes on the right) than 5 psi (three syringes on the left). These syringes were coated under the condition of 22–10 mm spraying range, 50 mm/s retraction rate, and 0.2 mg target silicone amount. It should be noted that the air pressure coming out of the nozzle orifice may be significantly lower than the air pressure set by the pressure gauge due to pressure drop along the path between the pressure gauge and the orifice. The true pressure at the orifice is difficult to measure or predict. Another effect of air-to-nozzle pressure is on the size of silicone droplets; on the same photo it appears that 15 psi produced smaller droplets than 5 psi, which facilitated more even distribution of silicone coating.

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Figure 6

Glass powder testing on syringes coated using the condition of 22–10 mm spraying range, 50 mm/s retraction rate, and 0.2 mg target silicone amount with two air-to-nozzle pressures, 15 psi (three syringes on the right) and 5 psi (three syringes on the left).

Optimization Considerations

The parameter investigation above was used to support the selection of optimum siliconization conditions. In the optimization test, we targeted a 0.3 mg silicone coating dose, which is near the low range of the preferred silicone amount. The selection of nozzle retraction rate was based on two criteria: (1) the retraction rate should be as fast as possible to shorten the coating cycle and increase production speed, and (2) the retraction rate should not be too fast to compromise distribution uniformity. Thus, the nozzle retraction of 100 mm/s was chosen from the range of 50 to 200 mm/s. Ideally, slow and long spray range should promote distribution uniformity. Since previously the spray range of 44 to 10 mm past the flange displayed acceptable distribution uniformity, we tightened the nozzle spray range to 35–10 mm past the flange to further benefit cycle time reduction. For air-to-nozzle pressure, 10 psi represents the mid-point of the tested range (5–15 psi) and appears to be appropriate because 5 psi might be too low to generate small droplets and 15 psi might be so high that it might disturb droplet flow for smooth deposition. In addition, to further improve the atomization condition to produce finer droplets without using higher air-to-nozzle pressure, silicone was heated to a higher temperature, in the range of 85–100 °C (see Figure 1b for the heating mechanism) to reduce viscosity prior to atomization.

Five syringes coated under the optimum condition were tested by the glass powder method. Coating distribution appears to be uniform across the entire barrel for all syringes except for slightly lighter coating in the area near the needle (Figure 7a). Although these syringes (n = 5) passed the glide force testing (Figure 7b), the glide force profile of two syringes shows a slight increase at the end of the stroke (after 30 mm past the flange), confirming the weaker coating by glass powder testing. In another set of coating experiments under the optimum condition but with heating at 85 °C, all five syringes successfully passed the glide force test with flat glide force even at the end of the stroke (Figure 7c), suggesting that heating indeed facilitated distribution uniformity. Overall, the selected coating condition with nozzle heating could coat a low dose of silicone with acceptable distribution uniformity. More importantly, this condition offered a short coating cycle suitable for large-scale manufacturing process and proved to be optimum.

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Figure 7

Glass powder distribution of (a) syringes coated under the optimum condition (0.3 mg target silicone amount, 100 mm/s nozzle retraction rate, 10 psi air-to-nozzle pressure, and 35–10 mm past the flange for the spraying range) and glide force testing of (b) five syringes above and of (c) another set of five syringes coated under the same optimum condition but with heating at 85 °C.

Correlation of Bench-Top Coating Unit to Semi-Automated, Pilot Siliconization System

This pilot unit used the same IVEK nozzle and pump system as the bench-top unit but the nozzle and pump were integrated into one piece (Figure 8). The movement of the pump/nozzle unit is mediated by a mechanical mechanism controlled by a servo gear. The advantage of this design is the elimination of tubing flex. With the understanding of key siliconization parameters through bench-top siliconization investigation, the development and optimization studies on this larger pilot unit can be significantly reduced.

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Figure 8

Pump and nozzle arrangement in the pilot-scale siliconization system.

To evaluate the performance of this pilot unit on silicone amount and distribution uniformity, syringes were coated with three levels of silicone amount (0.2, 0.5, and 1.0 mg) using 10 psi air-to-nozzle pressure, 100 mm/s nozzle retraction rate, and 42–0 mm spray range. These are the optimum coating conditions derived from the bench-top study except for a wider spray range. The use of the wider spray range is mainly to ensure the needle end of the barrel can be effectively coated, particularly for the 0.2 mg group. In this experiment the nozzle was heated to 100 °C. Table III summarizes the coating amount results (n = 20). The averaged coating amount matched well within the targeted specification. In addition, all three groups showed a similar standard deviation (SD) at ∼0.05 mg. When comparing spray performance, particularly on the 0.2 mg target level between the bench-top units, this pilot unit indeed outperformed the bench-top unit (also in Table III based on 90 samples from Figure 4). With a similar averaged coating amount, 0.27 vs 0.24 mg, the SD is 0.05 mg for the pilot unit vs 0.07 mg for the bench-top unit. The most significant difference is that the bench-top unit resulted in one syringe with no silicone coating, which was attributed to tubing flex previously. For the pilot unit, the least-coated syringe is 0.16 mg. All three groups passed the glide force test (n = 5, Figure 9a), and the glass powder test (Figure 9b) confirmed the distribution uniformity for all targeted levels. This experiment demonstrated that the optimum coating condition derived from the bench-top unit is transferable to the pilot-scale unit. This optimum condition may be applicable to an even larger manufacturing-scale siliconization system if based on a similar coating mechanism and equipment components, such as nozzle, pump, and so on, because the scale-up strategy is to use multiple nozzles simultaneously instead of a faster coating cycle.

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Figure 9

Instron glide force profile for the 0.5 mg/syringe target (a) and glass powder testing (b) for syringes prepared using the BAT semi-automatic pilot siliconization unit.