Protecting the actives in your premix

The objectives of feed supplementation are to manufacture medicated feeds whose concentration in active ingredients fulfils with two criteria: conformity and homogeneity.
Conformity is defined as consistency between active ingredient theoretical and actual mean concentrations in feed. Conformity can be impacted by degradation of the active ingredient during feed manufacture or during storage.

Homogeneity is defined as the acceptable range in distribution of the active ingredient concentration in medicated feed. Homogeneity can be impaired by demixing occurring during feed manufacture.

Amoxicillin is widely used in feed for the control of pig bacterial infections due to Streptococcus suijsHaemophilus parasuisor respiratory pathogens. Nevertheless diferent factors can lead to amoxicillin degradation during medicated feed manufacture and storage: high temperature, humidity, and feed components such as enzymes.

In order to protect amoxicillin from degradation, a specific hydrophilic coating process has been developed (Stavibac patented process, Virbac). Compared to crystalline particles of standard amoxicillin (median particle size: around 20μm), coated amoxicillin is made of spherical particles inside which amoxicillin is protected (median particle size: 380μm, Figure 1).

Comparative stability studies between standard amoxicillin premix and Suramox premix (containing Stavibac amoxicillin, Virbac) have been performed in order to check amoxicillin concentration in feed after pelleting and during medicated feed storage. Standard pig starter feeds and usual pelletization conditions were used. Amoxicillin assay in feeds was performed by high performance liquid chromatography.
In a first study, pelleted feeds were checked over a six months after pelleting (storage conditions: 25°C and 60% relative humidity).

Amoxicillin concentration in pelleted feeds supplemented with Suramox remained above 95% of initial content. In feeds supplemented with standard amoxicillin premix, an initial amoxicillin relative degradation of 19% was observed after pelleting. A regular decline was then recorded over the sixmonth storage period, down to 35% of initial content before pelleting (Figure 2).

In a second study, four medicated feeds were stored at 40°C with a relative humidity of 100% during one month.

No degradation of amoxicillin was noticed in feeds supplemented with Suramox whereas relative degradations of 41% and 64% were observed in feed supplemented with standard amoxicillin premix after 8 days and 30 days of storage, respectively (Figure 3).

Therefore the Stavibac coating process protects amoxicillin from degradation during feed pelleting and during feed storage even according to drastic conditions (temperature, humidity).
Demixing of medicated feeds can occur by difeerent phenomena among which elutriation. Elutriation is a demixing phenomenon due to diferent speeds of powder particles while falling through the air. This process often occurs during transfer of feeds through ducts in plants.

A standardized test has been developed by a Technical Research Centre for Feedstufs (Tecaliman, This test consists in dropping a homogeneous medicated feed sample in an 8m high tube. After fall, top and bottom feed samples are taken for antimicrobial assay. A tracer is also assayed to validate the test. An elutriation index (EI) is calculated to quantify the demixing by elutriation: France) to assess elutriation potential of medicated premixes in feed.

Where Ct and Cb are respectively concentrations in top and bottom samples.
This index ranges from –200 to +200, extreme values corresponding to maximal demixing whereas zero value corresponds to lack of demixing.

This test has been correlated with demixing of supplemented feeds in plants: the higher the elutriation index, the higher the risk of demixing between plant feed mixer and plant feed outlet. The elutriation test has been applied to Suramox premix in two starter feeds difering by median particle size (respectively 420μm and 276μm).

In both feeds elutriation index was low, thus showing limited demixing. By comparison, this index was 4-fold higher with a standard amoxicillin premix, exhibiting a significant demixing.
Elutriation index of the tracer (known for its ability to demixing) was in the same range as the index obtained with standard amoxicillin (Figure 4).

Low demixing with Suramox can be explained by particle size of Stavibac amoxicillin (median: 380μm) consistent with particle size of pig feeds. On the contrary, standard amoxicillin is much thinner (median particle size: circa 20μm).

Thus during the elutriation test, standard amoxicillin particles fall more slowly than majority of feed particles, inducing a segregation of amoxicillin inside top of the sample after test. As a consequence, a positive elutriation index around 100 is obtained, increasing the risk of demixing in feed plants according to the correlation above mentioned between elutriation test and demixing of industrial batches.

In conclusion the amoxicillin coating process described here fulfils with requirements of feed supplementation, ie conformity and homogeneity of active ingredient concentration in feed. This specific hydrophilic coating process does not delay in vitro dissolution of amoxicillin, thus having no negative effect on amoxicillin oral absorption whereas other types of hydrophobic coating process have been shown to reduce amoxicillin oral absorption in pigs.

by Eric Bousquet - Virbac