What is Bioavailability?

Bioavailability refers to the speed and extent to which drugs in the preparation are absorbed into the human circulation. Bioavailability is the ratio of the amount of a given drug that enters the body's circulation. It describes the percentage of the oral drug that is absorbed by the gastrointestinal tract and passed through the liver to the systemic blood. Including the degree of bioavailability and the rate of bioavailability.

Bioavailability refers to the speed and extent to which drugs in the preparation are absorbed into the human circulation. Bioavailability is the ratio of the amount of a given drug that enters the body's circulation. It describes the percentage of the oral drug that is absorbed by the gastrointestinal tract and passed through the liver to the systemic blood. Including the degree of bioavailability and the rate of bioavailability. ^[1]

The concept of bioavailability was proposed by oser in 1945. Since the 1960s, some pharmaceutical preparations have been found to comply with the pharmacopoeia of the time. The chemical composition is the same and the content is the same, but when used in animals and humans, the blood concentration and absorption rate Different and serious medical accidents caused by repeated drug bioavailability problems have been fully recognized and acknowledged. For example, the phenytoin sodium tablets produced in Australia in 1968 have consistently good effect on patients. Later, some people changed the supplementary CaSO ₄ in the prescription to lactose, and the others did not change. As a result, continuous poisoning incidents occurred during clinical application, which attracted special attention. After research, it was found that after changing the CaSO ₄ in the prescription to lactose, the in vitro release and in vivo absorption of the compressed tablets were greatly improved, causing the blood drug concentration to exceed the minimum poisoning concentration, so a poisoning event occurred, so its research has been increasingly People value it.

In vitro studies on bioavailability Generally, the dissolution studies of oral drugs are used as control indicators. For example, the United States Pharmacopeia (USP) in 1970 stipulated that some preparations should be subjected to in vitro dissolution tests as indicators to control bioavailability in the future. More and more preparations contained in the Pharmacopoeia of various countries need to be subjected to in vitro dissolution testing. The appendix of the Chinese Pharmacopoeia since 1975 (Part Two) records the dissolution test methods for tablets, capsules, and solid dosage forms, and half of the 1995 edition has The above tablets and capsules need to be measured for dissolution.

Bioavailability in vivo studies are usually based on the area under the plasma drug concentration-time curve (C-t curve) (AUC) and the highest blood concentration (peak concentration, peak, Cmax) that can be reached after administration and the highest blood concentration Time (peak time tmax). ^[2]

Many factors affect the bioavailability of oral medications, such as:

Physical and chemical properties of the compound: stereochemical structure (including chirality), ratio of entering the cell membrane, molecular weight, molecular volume, pKa, solubility, permeability, hydrophilic and lipophilicity, compound stability, partition coefficient, dosage form properties (such as disintegration Time limit, dissolution rate) and some process conditions.

Gastrointestinal tract environment and anatomical and physiological status: the role of fluids in the gastrointestinal tract (intestinal pH, bile effects, lymph fluid flow, etc.), drug transport in the gastrointestinal tract (various specific transport systems in small intestinal epithelial cells And multidrug resistance (MDR), p-glycoprotein, etc.), the surface area of the absorption site and local blood flow, the effects of drug metabolism, intestinal strains, etc.

Other factors: pathological status, genetic differences, individual differences, ethnic differences, drug interactions, drug and diet, nutrition interactions, etc. ^[3]

The reasons for the low bioavailability of oral drugs can be summarized into three types: less drug solubility and dissolution rate; poor gastrointestinal mucosal permeability of drugs; and rapid elimination of drugs in the body. The improvement methods based on the low solubility and dissolution rate of drugs leading to low bioavailability of oral drugs are mainly based on methods such as increasing the surface area of drugs, increasing the solubility of drugs, or a combination of two methods, such as traditional salt formation and increasing solubilization , Cosolvent and other methods. In addition, by changing the molecular structure of poorly soluble drugs, selecting appropriate carriers and formulation technologies to improve their physicochemical properties, their affinity with the gastrointestinal mucosa and their permeability, etc., and also improving their oral bioavailability Effective methods, such as ultra-fine pulverization technology, solid dispersion technology, molecular inclusion technology and emulsification technology developed in modern times. The improvement methods based on the poor permeability of the gastrointestinal tract mucosa due to the low oral bioavailability of drugs are mainly based on methods such as the use of absorption enhancers and prolonged drug retention time in the gastrointestinal tract. Residual preparations, etc., some drugs that are actively absorbed in specific parts of the gastrointestinal tract can be made into localized release preparations. Because the elimination of drugs is mostly proportional to the concentration of the drug, slowing the release of the drug and maintaining the blood concentration at a relatively low concentration can slow the elimination of the drug, so the drug that is quickly eliminated in the body is made slower. Controlled release formulations may improve bioavailability. In addition, some of these methods, such as microemulsion technology, may have multiple effects such as increasing the surface area of the drug, increasing the solubility of the drug, and promoting the absorption of the drug. Surfactants limit the widespread use of microemulsion technology. ^[3]