- (1) Biological half-life: For drugs with a short half-life, if sufficient controlled release is to be maintained, the dose per unit of dosage must be large, resulting in an increase in the dosage form. In general, drugs with a half-life of less than one hour are not suitable for use as a slow release form. Drugs with a long half-life (t1/2>24h) have a long-lasting effect, and generally do not use controlled-release formulations.
- (2) Absorption: The purpose of preparing a sustained-release formulation is to control the release rate of the drug, which generally is much slower than the absorption rate. Most drugs run in the gastrointestinal tract for 8 to 12 hours, and the absorption half-life is approximately 3 to 4 hours. If the drug is released too slowly, the drug has not been completely released before they left the absorption site, resulting in low bioavailability. Therefore, a drug having a very low absorption rate constant is not suitable for a controlled release formulation.
- If the drug is absorbed by active transport, or is absorbed in a specific part of the small intestine, it is not suitable for the controlled release of the drug to be absorbed. For example, riboflavin is mainly absorbed by active transport at the upper end of the small intestine, so it is not suitable for making a controlled release agent. Although riboflavin is present in multivitamin controlled release preparations, it has been demonstrated that the controlled release formulation does not have any superiority compared to the conventional preparation.
- (3) Metabolism: If a drug that has a metabolic effect before absorption, then the bioavailability of a sustained-release drug is generally reduced, because most of the intestinal wall enzyme system's drug metabolism is saturated. If a small amount of drug continues to be slowly released into these areas, the action of the enzyme will convert a larger amount of the drug into a metabolite. Designing such drugs as controlled release formulations can significantly reduce the bioavailability of the drug. If the drug can be combined with a specific enzyme inhibitor to form a controlled release preparation, such as levodopa and a dopa-decarboxylase inhibitor together with a controlled release preparation, the drug absorption can be increased, and the therapeutic effect can be prolonged.
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