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Analysis on the role of drug dissolution test in the determination of human bioavailability

2021-02-18
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The dissolution rate and extent of solid dosage forms such as tablets, capsules, or granules in a prescribed medium refer to the dissolution rate of the drug. Since the dissolution of the drugwill directly affect the absorption and utilization of the drug in the body, the drug dissolution test is an important indicator to evaluate the quality of the drug preparation and the production process. The dissolution of oral solid preparations is an important factor that affects the bioavailability of the human body. For the determination of the bioavailability of the human body, the dissolution test can be used to effectively evaluate it. Analyzing and researching various factors that affect the dissolution rate of solid preparations, and formulating a reasonable prescription and process design are essential to improve the bioavailability of poorly soluble drugs and ensure the bioequivalence of drugs.

drug development

Drug preparations that are poorly soluble in water are one of the types of drugs that require dissolution testing as specified by the Pharmacopoeia. Recent studies have shown that in addition to poorly soluble drugs have dissolution problems, easily soluble drugs can also cause drugs due to different formulations and processes. The difference in dissolution rate, which affects the bioavailability and efficacy of the drug.

Correlation between in vitro dissolution rate and in vivo bioavailability

Bioavailability refers to the speed at which the drug enters the target organ or tissue and the extent to which it is used by the target organ. Studies have found that the bioavailability of different dosage forms of pharmaceutical preparations with the same content are different, and the bioavailability of the same dosage form produced by different manufacturers, or even products with different batch numbers produced by the same manufacturer, is not consistent. Drugs or preparations with different bioavailability must have different efficacy. In vitro correlation refers to the correlation between the changes of pharmaceutical dosage forms in vitro and their biopharmaceutical-pharmacokinetic changes in vivo, and is a function of in vitro dissolution and in vivo bioavailability parameters. The purpose of studying the in vivo and in vitro correlation of a certain pharmaceutical preparation is to establish an in vitro quality standard that can explain the bioavailability and use it as a quality control index for the mass production of the preparation.

Because the operation process of drug bioavailability test is more complicated than that of dissolution test, in actual work, for drugs with good in vivo and in vitro relevance, the in vitro dissolution rate is measured to predict the in vivo bioavailability of poorly soluble drugs, and then screen The formulation of preparations and the control of their quality are of great significance.

Research content of drug dissolution test

The drug dissolution test is generally formulated to simulate the state of the drug preparation in the gastrointestinal tract, usually in terms of temperature, rotation speed, medium pH and enzymes. The purpose of the in vitro dissolution test is to understand the biopharmaceutics of the preparation and predict the release and absorption of the drug in the body, so that the data obtained in vitro release can be more closely correlated with the data in vivo. The second part of the Chinese Pharmacopoeia (2005 edition) mainly uses ultraviolet spectrophotometry and HPLC to determine the dissolution of drugs. The content of the dissolution determination research includes the comparison test of the pulp method and the rotating basket method; the certification of the detection method, including the recovery rate test and the linear relationship test, etc.; the drawing of the dissolution curve; the rotation speed selection; the determination of the blood concentration in the body; the dissolution rate The test is a one-of-a-kind test; selection of dissolution media; determination of dissolution correlation and pharmacokinetic parameters.

When the dissolution rate of the drug is equal to or lower than the absorption rate of the drug in the body, the dissolution rate becomes a time-limiting factor, and there may be a certain correlation between the two. If this correlation is good, the results of the in vitro test are meaningful for predicting the behavior of the drug in the body.

In vitro dissolution test to evaluate the bioavailability of ibuprofen sustained-release capsules

The data obtained from the dissolution test is processed to obtain some parameters, and the quantitative relationship between the in vivo drug absorption characteristics calculated from the blood drug concentration data is established, that is, the relationship between in vitro dissolution characteristics and in vivo drug absorption characteristics. This relationship can be described by linear equations. Taking ibuprofen sustained-release capsules as an example, first calculate the cumulative dissolution rate and the absorption percentage (F%) at each time through the in vitro dissolution test; then take 0.2ml of blank blood, and precisely add different concentrations of ibuprofen standard solutions. , Make the plasma concentration respectively 0.5, 1, 5, 10, 20 and 40μg/ml, the plasma sample is processed, chromatographic separation and determination are performed, and finally the standard equation is obtained by linear regression of the peak area (A) against the concentration (C).

The results show that the method has a good linearity within 0.5-40μg/ml; at this time, the subjects’ plasma samples at different times are taken, processed and injected, and the measured plasma drug peak area values are substituted into the plasma standard curve equation to calculate Calculate the blood drug concentration; finally, take the absorption fraction at time t as the dependent variable F and the cumulative in vitro dissolution percentage at the corresponding time as the independent variable X. Use the least squares method to regress to obtain the in vivo and in vitro correlation data, and obtain the correlation equation. There are significant differences between the two Correlation. Once the dissolution rate results are correlated with the blood drug concentration in the body, the in vitro dissolution test can effectively control the bioavailability of the drug formulation.

In addition, it is also possible to obtain the dissolution characteristics in the body by the deconvolution integral method or use the principle of statistical moment analysis to obtain the average residence time in the body and the average dissolution time in the body. Then establish the correlation between the in vivo and in vitro parameters, and the result can indicate whether the correlation of the preparation is significant. If there is a significant correlation in vivo, a dissolution test can be used to effectively evaluate the in vivo bioavailability of the drug. You can start with this newer quality control method and select the appropriate prescription and process conditions.

The test results of drug dissolution testing have a certain correlation with the results of in vivo and in vitro drug bioavailability. The dissolution test is to evaluate the bioavailability of drugs and to research alternative methods, and also to evaluate the quality difference of each batch of solid oral dosage forms. And drug quality control methods can ensure the production process of solid pharmaceutical preparations. With the development of work on bioavailability, the scope of dissolution work is gradually increasing. It can not only be applied to tablets, but also widely used in other dosage forms, and even some preparatio

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