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  5. Laboratory Study Shows Oral Antacid Drug Performs Differently When Mixed with Various Food Vehicles
  1. Spotlight on CDER Science

Laboratory Study Shows Oral Antacid Drug Performs Differently When Mixed with Various Food Vehicles

Generally, patients prefer to take drugs by mouth (orally).1 Solid oral drugs, such as capsules and tablets, are common because they are cost-effective to make, and it is easy to scale up production. However, many patient populations — including children, older adults, and those with cancer or neurological conditions — may have a condition called dysphagia, leading to difficulty swallowing solid foods or medications.

“Sprinkling” a drug into food vehicles can be an alternative for these patients. Sprinkle formulations are drug-containing pellets or granules that can be mixed with soft foods or drinks before administration.1 Sprinkling can improve patient compliance. More than 75% and 93% of children preferred drugs sprinkled into their foods to syrup and oral drops, respectively.1

While food vehicles help patients take their medications, it is important that these vehicles do not affect the medication’s safety and effectiveness. Research2 has shown that mixing incompatible foods and drugs may impact the drug’s rate of dissolution in the gastrointestinal tract, potency (strength), and may even lead to undesired side effects. On a related note, researchers are also interested in efficient ways and methods to analyze food vehicles’ effect on medication, such as in vitro (laboratory) studies instead of typically more time-consuming in vivo (in living organisms) studies.  

To those ends, CDER researchers recently conducted a study on this topic, The effect of food vehicles on in vitro performance of pantoprazole sodium delayed release sprinkle formulation.2 Researchers focused on pantoprazole sodium, which treats stomach and esophagus problems, such as gastroesophageal reflux disease, by decreasing the amount of acid the stomach makes. Current pantoprazole sodium labeling advises patients to mix the medication with applesauce or apple juice, as supported by in vivo data described in the labeling.3

Researchers wanted to see if an in vitro test would produce consistent results, which could show the potential of using in vitro testing in this capacity. This can accelerate development of generic versions of products and ensure the generic products can be used in accordance with the product labeling. As of now, generic versions of pantoprazole sodium delayed release (DR) granules need to include an in vivo study examining the drug mixed with applesauce.

The study evaluated several food vehicles and their effect on the in vitro performance (i.e., the process of dissolving in the body) of the drug. Researchers chose apple juice and applesauce, as well as pudding, yogurt, and milk. The foods differed in their viscosity (thickness), pH level (or how acidic/basic an item is), and water content.

In the study, the researchers sprinkled the pantoprazole sodium granules on the food vehicles for different amounts of contact time (30, 60, or 120 minutes). Then they placed the mixture into a dissolution apparatus for in vitro dissolution testing and took samples after various time periods. They evaluated the in vitro performance of pantoprazole sodium DR granules in the different environments and made comparisons across the food vehicles as well as the control group, which was the DR granules not mixed with any food.

Researchers found that the food’s pH and the length of time it was mixed with the drug affected drug performance. When researchers mixed the drug into low pH food vehicles, such as applesauce or apple juice, the drug performed similarly to the control group. Conversely, high pH food vehicles, such as milk, with a long contact time (e.g., 120 minutes) caused premature drug release, drug degradation, and loss of performance. Interestingly, drugs mixed in the high pH foods for short time durations, like 30 or 60 minutes, had little performance change, although researchers did observe more deformed drug granules.

In conclusion, researchers confirmed that an in vitro assessment can detect the effect of the food vehicle on drug performance, which has implications for evaluating drug safety and efficacy. For pantoprazole sodium, researchers found that mixing the drug with milk and pudding can change in vitro performance compared to apple juice and applesauce, which are the food vehicles recommended for use in the label. This is consistent with our previous understanding. The study shows the potential of in vitro studies to analyze a drug’s performance in different food vehicles.

It is important to use the recommended food vehicles for sprinkle administration, and patients should ingest all the food vehicle-drug mixture to get the full benefits of the drug.

1 Lee HS, Lee JJ, Kim MG, et al. Sprinkle Formulations-A Review of Commercially Available Products. Asian Journal of Pharmaceutical Sciences. 2020 292-310. https://doi.org/10.1016/j.ajps.2019.05.003

2 Wu KW, Zheng K, Tian L, et al. The Effect of Food Vehicles on In Vitro Performance of Pantoprazole Sodium Delayed Release Sprinkle Formulation. International Journal of Pharmaceutics. 2023, Vol. 635, 122737.

3 Pantoprazole Sodium Drug Labeling. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/020987s058,022020s021lbl.pdf. Accessed June 6, 2023.

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