Technical Bulletin No.     CD 0448

A Comparison of Aureo S 700® and Pennfield CTC+SMZ Premixes

Introduction

Aureo S 700 was approved in 1968 for cattle as an aid in the maintenance of weight gains in the presence of respiratory diseases such as shipping fever. Aureo S 700 Premix contains 35 g/lb each of Aureomycin chlortetracycline (CTC) and sulfamethazine (SMZ), and is added to cattle feed to provide an intended level of 350 mg/head/ day of each antimicrobial component. Aureo S 700 is totally granular, and each granule contains both Aureomycin and SMZ in a 1:1 ratio. The original dose titration studies for Aureo S 700 confirmed that this ratio was optimal for maintaining growth.1   Calves receiving Aureomycin alone at 350 mg/hd/day showed a 4.2% improvement in ADG over nonmedicated controls, but when sulfamethazine at 350 mg/hd/day was added to the diet, calves showed a 19.7% improvement (Table 1).

TABLE 1. Aureo S 700 historical dose titration studies.

Pennfield CTC+SMZ premix also is labeled to contain 35 g/lb each of CTC and SMZ. Microscopic examination of the premixes suggests that the Pennfield premix is not totally granular; rather, only the SMZ component is granular while the CTC is a meal. Microscopic analysis further shows that the Pennfield premix carrier is comprised of different materials than that found in Aureo S 700, and that while the Aureo S 700 premix particles are bonded (agglomerated) to their carrier, the Pennfield product has been blended with its carrier but not bonded to it and, thus, appears susceptible to segregation.2   Previous research comparing granular and meal premixes show advantages for granular in handling and flowability, distribution in feed, drug stability during feed manufacturing, and reduced carryover potential.3-10    A recent study comparing Aureo S 700 and Pennfield CTC+SMZ premixes was conducted by Behnke et al. at Kansas State University. The study confirmed that Aureo S 700 and Pennfield CTC+SMZ premixes are physically different products that have different performance in feed manufacturing.

Materials and Methods

The study was designed to manufacture 2 g/lb (4000 g/ton) crumbles, and while doing so, to evaluate a number of parameters including premix potency; premix particle size and drug activity distribution; flowability and handling; pelleting stability; and carryover potential. The study was conducted by Dr. Keith Behnke, a feed manufacturing expert from Kansas State University’s Grain Sciences Department, using the on-campus feedmill. The test premixes were obtained through distribution and confirmed to be within their expiration datings. Each premix was added to the feed based on the labeled level of drug (35 g/lb). Afterwards, samples of each premix were collected and submitted for potency verification using HPLC methodology. Feed samples were collected and assayed using microbiological and HPLC methodology for CTC and SMZ, respectively.

The horizontal ribbon mixer used for this study was thoroughly cleaned prior to the start of the study. For each premix, the following sequence of events occurred:
  1. one 500-lb batch of nonmedicated feed was made;
  2. one 500-lb batch of medicated feed was made and samples collected at various points of manufacture;
  3. one 1000-lb batch of medicated feed was made and samples collected at various points of manufacture;
  4. system was flushed with two 150-lb batches of flush material and samples were taken after each flush;
  5. clean-out of residual feed and sample collection.

Results

PREMIX POTENCY
The Aureo S 700 premix assayed at 107% and 103% of label for Aureomycin and sulfamethazine, respectively. The Pennfield CTC+SMZ premix assayed at 97% of label for CTC and 95% of label for SMZ. While both premixes were within FDA assay limits for Type A premixes (85-115%), the Pennfield premix supplied 10% less CTC and 8% less SMZ than the Aureo S 700 premix. Furthermore, the Pennfield premix would not have met Alpharma’s Potency Guarantee of 100% of label or better (Table 2).

PARTICLE SIZE AND DRUG ACTIVITY DISTRIBUTION
Based on the sieving analysis conducted at KSU, 60% of the Aureo S 700 premix consisted of larger-sized particles (>60 screen US, which is the "gold standard" for particle size), compared to only 35% of the Pennfield premix (Figure 1). When the Aureo S 700 larger-particle sieve fraction was assayed for drug activity, it was found to contain 63% of the Aureomycin activity and 60% of the SMZ activity vs 26% of the CTC activity and 4% of the SMZ activity for the Pennfield larger-particle fraction. This means that 74% of the CTC activity and 96% of the SMZ activity in the Pennfield premix were found in the fines and dust. Note also that the ratio of CTC:SMZ was near the desired 1:1 for the Aureo S 700 larger-particle fraction vs 6.5:1 for the Pennfield premix. This signifies uneven distribution of drug components within the Pennfield CTC+SMZ premix, promoting uneven distribution within the manufactured feed and potentially compromising antimicrobial efficacy in the calf.
FLOWABILITY AND HANDLING RESULTS
The angle of repose is a measurement used to determine flow characteristics of a given product. The data can be used to determine how well a product moves through a mill system. The lower the number, the better the flowability and the reduced tendency for bridging in the microingredient bin system.7   The angle of repose was 22% less for Aureo S 700 than for the Pennfield CTC+SMZ premix (Figure 2). This suggests that the Aureo S 700 premix will handle much better during feed manufacture, helping to ensure that the targeted level of medication ends up in the feed. Further, using Aureo S 700 could help to improve mill throughput by reducing the downtime required to address premix flowability and microbin bridging issues.

TABLE 2. Average premix potency for Aureo S 700 vs Pennfield CTC+SMZ.

FIGURE 1: Premix larger particle size and activity distribution for Aureo S 700 and Pennfield CTC+SMZ. FIGURE 2: Comparative flowability of Aureo S 700 vs Pennfield CTC+SMZ.

FIGURE 3: Percent potency loss during pelleting for Aureo S 700 vs Pennfield CTC+SMZ. FIGURE 4: Reduced sulfamethazine carryover potential with totally granular Aureo S 700.

STABILITY DURING PELLETING RESULTS
Multiple representative feed samples were collected pre- and post-pelleting and used to determine the average potency loss during pelleting. Pelleting temperature was approximately 180°F. For the Aureo S 700 premix, the Aureomycin retained 100% of its potency and the SMZ lost only 1.9% potency (Figure 3). For the Pennfield CTC+SMZ premix, the CTC lost 13.3% potency and the SMZ lost 8.5% potency. Larger particles have a decreased surface area compared to smaller particles.6   The increased potency loss seen with the Pennfield CTC+SMZ premix was likely due to the larger surface area associated with its higher percentage of fines and dust. As discussed earlier, the fines and dust held most of the drug activity for the Pennfield premix, and this larger surface area allowed increased drug exposure to the debilitating heat and moisture associated with the pelleting process. The pelleting stability evaluation also demonstrated another key point: all granules are not created equal. Though both Aureo S 700 and the Pennfield premix contain granulated sulfamethazine, the SMZ in Aureo S 700 retained its potency during pelleting much better than did the Pennfield SMZ.
REDUCED CARRYOVER WITH TOTALLY GRANULAR AUREO S 700
In 1983, Dr. Gary Cromwell, University of Kentucky, compared the sulfa carryover potential of a totally granular premix (Aureo S-P 250®) to that of a partially granular premix (i.e., only the SMZ was granular).8   Cromwell found that sulfa levels in mixer dust were 50% lower in feed manufactured with the totally granular vs partially granular premix. In the current study, as expected, residual sulfamethazine levels for both premixes were substantially reduced with the 1st flush (Figure 4). With the 2nd flush, the SMZ dropped to non-detectable levels for Aureo S 700. However, the Pennfield premix left a large amount of residual SMZ in the feed manufacturing system, as there was a sizeable amount of SMZ present in the 2nd flush. Clearly, additional flushes would be required to reduce the SMZ residue created by the Pennfield premix to a non-problematic level.

Conclusions

  • The Aureo S 700 premix met and exceeded the labeled potency, while the Pennfield CTC+SMZ premix did not.
  • The Aureo S 700 premix had 42% more larger-sized particles than the Pennfield premix.
  • The majority of Aureo S 700’s antimicrobial activity was found in the larger-sized particles, while most of the Pennfield premix activity was in the fines and dust, which are more easily lost during the feed manufacturing and delivery process.
  • Totally granular Aureo S 700 is formulated so that each granule contains both Aureomycin and SMZ in the optimal 1:1 ratio. With the Pennfield CTC+SMZ premix, only the SMZ is granular while the CTC is meal, promoting segregation and uneven distribution of antimicrobial components in the premix and in the feed.
  • Aureo S 700 had a 22% lower angle of repose than the Pennfield premix , signifying better handling and flowability characteristics and a reduced propensity for bridging in the microbin system.
  • Aureo S 700 withstood the rigors of pelleting better than the Pennfield CTC+SMZ premix, retaining almost all of its antimicrobial activity while the Pennfield premix lost 13.3% of its CTC activity and 8.5% of its SMZ activity.
  • The better pelleting stability seen with Aureo S 700 also showed that all granules are not created equal. Compared to the Pennfield SMZ granule, the Aureo S 700 SMZ granule better withstood the heat and moisture associated with pelleting.
  • Totally granular Aureo S 700 showed a reduced potential for SMZ carryover compared to the partially granular Pennfield CTC+SMZ premix.
  • The above points confirm the 'take-home message' for this study: Aureo S 700 is superior to Pennfield CTC+SMZ for feed manufacturing.

References

  1. Cyanamid Animal Feed Product Reference. 1978.
  2. Bates LS. Alteca Ltd. Consulting Laboratory and Technical Center. Manhattan, KS. 2003.
  3. Alpharma Inc. Comparison of Aureomycin chlortetracycline granular premix to generic chlortetracycline meal premix. Technical Bulletin RCD 9283.
  4. Alpharma Inc. Comparison of mixing characteristics of Aureomycin granular premix and two generic chlortetracycline meal premixes. Technical Bulletin RCD 9321.
  5. Alpharma Inc. Comparison of segregation and active ingredient retention of Aureomycin granular premix and generic chlortetracycline meal premix in feed from mixing through delivery. Technical Bulletin RCD 9317.
  6. Alpharma Inc. Quality of Aureomycin granular premix vs. chinese generic chlortetracycline premix. Technical Bulletin RCD 9419.
  7. Alpharma Inc. The effect of premix formulation on flowability in microingredient bins. Technical Bulletin SD 0318.
  8. Cromwell GL. Whipping the sulfa residue problem in pork. Feed Management 1983; February.
  9. Laing N. Granulated ingredients: reducing drug potency loss. Feed Management 1994; December.
  10. Wolff T. Evaluation of premix characteristics and pelleting stability for Aureomycin granular and Terramycin® meal premixes in a large midwestern USA feedmill. Proc Amer Assoc Swine Practitioners 2003.




Aureomycin,® Aureo S 700,® and Aureo S-P 250® are registered trademarks of Alpharma Inc.
Terramycin® is a registered trademark of Phibro Animal Health.
Data in Alpharma research file.

Copyright © 2003 Alpharma Inc. All rights reserved.

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