The Mystery of the Drug Case: "Escape Plan"

Author: Shi Yanling

"Golden Cicada Shedding its Shell" refers to the cicada shedding its shell when it turns into an adult. It is a metaphor for escaping cleverly so that the opponent cannot detect it in time. This is also the 21st of the famous Thirty-Six Stratagems. This technique is used by people from insects to humans. Now let's introduce the "Golden Cicada Shedding its Shell" in the pharmaceutical industry. The story begins with a consultation at a pharmacy clinic......

One afternoon, my colleagues and I were sorting documents in the pharmacy clinic as usual. Suddenly, an uncle came in excitedly and said, "Pharmacist, I have a question!" Then he took out a plastic bag and took out the wrapped pills, and then said, "This is the pill I took yesterday. I pulled it out today intact! Look, this is the pill that was pulled out! Was this medicine absorbed? Is there a problem with the quality of the medicine!" The uncle became more and more excited and indignant. My colleagues and I walked closer to look at the pills and immediately recognized that they were the antihypertensive drug nifedipine controlled-release tablets. I understood the reason in my heart. The small pill seemed to be crying out for injustice, so we comforted the uncle and explained in detail to the uncle to "vindicate" the small pill.

The principle of the drug " Jinchan Shehu "

Nifedipine controlled-release tablets are covered with two layers of high-tech "outer coats". The outer layer is a "moisture-proof coat" to prevent moisture intrusion, and the inner layer is a semipermeable membrane coat (insoluble skeleton structure) with laser-punched micropores. The two layers of "clothes" wrap the drug layer and the booster layer.

After the nifedipine controlled-release tablets enter the human body, the "moisture-proof coat" dissolves in the digestive tract, and the booster layer absorbs water and swells, slowly increasing in volume, pushing the drugs in the drug layer to be released quantitatively and evenly from the micropores, keeping the blood drug concentration constant. The drug effect lasts for up to 24 hours, exerting a steady and lasting effect of lowering blood pressure, and only needs to be taken once a day.

After the active ingredients of nifedipine controlled-release tablets are absorbed, the empty tablets are excreted intact through the intestines, and intact tablets can be found in the feces [1], just like "a cicada shedding its shell", so the phenomenon of being excreted intact as mentioned by the uncle in the previous article occurs. In addition to nifedipine controlled-release tablets, the hypoglycemic drug glipizide controlled-release tablets also have a similar structure and will also "shed its shell" after being taken.

The mystery was solved and the "wrongful charge" of nifedipine controlled-release tablets was cleared. After listening to the explanation, the uncle left with satisfaction.

I thought the story was over, but it wasn't. A few days later, the uncle came to the pharmacy clinic for consultation again. This time, the uncle took out the packaged nifedipine controlled-release tablets. My colleague and I looked at each other in bewilderment. Didn't we explain it clearly last time?

The uncle said slowly: "Pharmacist, after listening to your explanation last time, I went home and soaked the tablets in a cup of warm water. I didn't observe any changes in the released medicine for the whole morning. When I took it out and touched it, it was still hard. What's going on?" It seems that the "injustice" of the small tablet has not been completely cleared, and the pharmacist is waiting to vindicate it.

Drug dissolution conditions

The absorption site of oral administration is the gastrointestinal tract. The pH value of gastric contents is 1.0-3.0, and the pH value of intestinal contents is 4.8-8.2[2]. The pH value, temperature and other conditions of warm water are very different from those of the human digestive tract. The dosage form of the drug is designed to simulate the physiological conditions of the human body. The drug can only be effectively released in the human body, and the release of the drug is not necessarily visible to the naked eye. Therefore, it is not possible to judge whether the drug is released normally based on the phenomenon observed when the drug is soaked in a cup of warm water.

My colleagues and I also reminded this adventurous uncle not to bite, chew or break open these tablets before taking them, because this would damage the "outer coat" of the tablets and expose the inner core containing the medicine directly. The medicine would be released quickly, resulting in the inability to maintain stable drug efficacy. It may also cause excessive absorption of the medicine in a short period of time and even cause drug poisoning.

The uncle suddenly realized what was going on, thanked him repeatedly and left. The story ends here. The two "wrongs" of nifedipine controlled-release tablets were cleared, and the truth of the "case" caused by the drug dosage form was revealed. The "escape plan" in the pharmaceutical industry is actually a product of high technology, which can help people better use drugs to treat diseases.

References:

[1]Nifedipine controlled-release tablets instructions. Bayer AG. 2021-10-21.

[2] Li Jun. Clinical Pharmacology. 6th Edition[M]. People's Medical Publishing House, 2018.