Comparison of solubility profiles for pioneer and generic monensin premixes in biorelevant simulated intestinal fluid based on shake flask extractions.

In the United States, a generic Type A medicated article product can gain the FDA approval by demonstrating bioequivalence (BE) to the pioneer product by successfully conducting a blood level, pharmacodynamic, or clinical BE study. A biowaiver can be granted based on several criteria, assuming the dissolution of the test and reference products represents the only factor influencing the relative bioavailability of both products. Monensin is practically insoluble in H2O per the USP definition. Previously published data from a comparison study of monensin dissolution profiles from the pioneer product and four generic products using biorelevant media showed that generic monensin products demonstrated different dissolution profiles to the pioneer product in these USP biorelevant rumen media. This follow-up study compared the solubility profiles in simulated intestinal fluid (cFaSSIF, pH 7.5) for the pioneer product and four generic products. The generic monensin products demonstrated different in vitro dissolution profiles to the pioneer product in biorelevant media. The differences demonstrated in solubility and dissolution profiles are of concern regarding the potential efficacy of generic monensin in cattle. There are also additional concerns for the potential development of Eimeria resistance in cattle receiving a sub-therapeutic dose of monensin from a less soluble generic product.

Investigation of monensin Type A medicated article dissolution profiles in biorelevant media.

In the United States, a generic Type A medicated article (premix) product can gain government approval by demonstrating in vivo bioequivalence (BE) to the pioneer product in a blood level, pharmacodynamic, or clinical BE study. A biowaiver can be granted based on several criteria including solubility or a dose adjusted method. Monensin is practically insoluble in H2 O per the USP definition. A comparison was conducted of monensin dissolution profiles from the pioneer product and four generic products using biorelevant media. Dissolution profiles were obtained in both Bovine Simulated Rumen Fluids - High Forage and High Grain diets. Data from twelve vessels (6 vessels per dissolution run × 2) were collected across 8 hrs for each lot and media. Data are reported as % dissolved, based upon the corresponding lot potency (mg/g). With demonstrated acceptable intra-lot variability, data were analyzed using f1 (difference factor) and f2 (similarity factor) procedures. The generic monensin products did not demonstrate similar in vitro dissolution profiles to the pioneer product in these USP biorelevant media. Differences in physical parameters (particle size, flow characteristics, and physical composition) were observed between the pioneer and generic products, but these differences had no apparent impact on biorelevant dissolution.