Enteric beads versus enteric coated tablets:
Which is the better option?
Enteric polymers have been used for decades by the pharmaceutical industry to prevent drug dissolution in the stomach. The decision to use an enteric polymer is based on one of three specific requirements for a drug. The most obvious use is for prevention of irritation to the stomach. In addition, some drugs degrade in the gastric environment. This not only results in loss of potency; the drug degradation products may also produce harmful side effects. Lastly, enteric polymers are sometimes used to target drug delivery to a specific region of the gastrointestinal tract.
One important property of enteric polymers has never received the attention it deserves, due to its impact on drug absorption. Rather than acting as an inert substance, enteric polymers undergo a dynamic transformation in the gastric environment. Longer gastric residence time and lower pH result in the polymer becoming gradually more resistant to dissolution in neutral intestinal fluid. Since the drug and polymer are moving through the gastrointestinal tract while dissolution occurs, increasing resistance to dissolution means dissolution may occur lower than expected in the gastrointestinal tract. However, the constantly changing physical properties of enteric polymers in the gastric environment has different implications for enteric beads and enteric coated tablets.
One of the functions of the stomach is to reduce larger materials to sub-millimeter particles. Enteric beads are typically below this size threshold and don’t require size reduction, so individual beads are free to begin exiting the stomach almost immediately after the dose is administered. Enteric beads exit the stomach independently, while those remaining in the gastric environment become gradually more resistant to dissolution. The effect produced by this process is a robust, extended drug release throughout the gastrointestinal tract, with relatively low day to day variability, within individual patients.
The same process produces the opposite effect on enteric coated tablets. Since tablets are typically much larger than the sub-millimeter size threshold for exiting the stomach, a prolonged and futile attempt at particle size reduction occurs before the tablet is passed to the small intestine. While enteric beads consist of multiple individual drug delivery units with variable dissolution properties, the enteric coated tablet is one drug delivery unit with a uniform dissolution property throughout the tablet coating. Depending on the pH and gastric residence time, an enteric coated tablet may dissolve soon after exiting the stomach or it may pass from the body intact, without any drug being absorbed. As a consequence, systemic exposure for a drug delivered via enteric coated tablets tends to be extremely variable across patient populations.
The action of the gastric environment on enteric beads makes them a useful option for extended drug release, as well as for prevention of gastric irritation and gastric drug degradation. The variable dissolution properties of individual enteric beads permits drug release from the upper small intestine and throughout the gastrointestinal tract. The same gastric acid effect on enteric coated tablets, coupled with the stomach’s attempt to reduce the tablet to particles, results in extremely variable systemic exposure. So while enteric beads are a useful addition to the formulations scientist’s toolbox, enteric coated tablets appear to be an undesirable option in all cases. The lesson here is that formulation choices for new medicines should be driven by clinical performance rather than by the marketing department's desire for an attractive tablet design.