Glimepiride belongs to the third generation of sulfonylureas and is widely used clinically in the treatment of type 2 diabetes. Tablets and pills are common dosage forms of glimepiride. Using in vitro dissolution tests to determine the bioavailability of glimepiride tablets and dropping pills can evaluate the quality of glimepiride in different dosage forms produced by different manufacturers. At present, there have also been multiple clinical trials to prove that glimepiride combined with metformin or saxagliptin also has a hypoglycemic effect with less adverse reactions.
Glimepiride is absorbed more quickly by oral administration. Compared with the first and second generation hypoglycemic drugs, it has better hypoglycemic effect, low incidence of hypoglycemia and less severe degree. It has become the most important drug in clinical practice. The plasma concentration of glimepiride reaches its peak 2 to 3 hours after taking it, and the duration is the longest. It is a long-acting preparation. Since the drug is excreted through dual channels, it can be used for diabetic patients with mild renal insufficiency.
The in vivo bioavailability measurement can reflect the clinical efficacy of the drug. The in vitro dissolution test can determine the drug dissolution curve in a variety of pH dissolution media under certain test conditions, and simulate and predict the release and absorption of the drug in various populations in vivo environments behavior. Bioavailability refers to the extent and speed at which the active ingredients of the drug are released and absorbed from the preparation into the systemic circulation. Medicilon can provide customers with bioavailability measurement services.
The Japanese study found that compared with the BE test, the dissolution test can sharply reveal whether the dissolution behavior of preparations from different sources is consistent. When the in vitro dissolution behavior of a generic drug is consistent with that of the original drug, not only is the probability of the two in vivo bioavailability consistent, but the probability of passing the BE test is also very high. Therefore, with the aid of discriminative dissolution test conditions, scientific and rigorous determination of the in vivo bioavailability of drugs will help to promote the improvement of pharmaceutical production processes, thereby enhancing the inherent quality and clinical efficacy of generic drugs.
The in vitro dissolution test is one of the important methods for evaluating the intrinsic quality of solid forms. For solid formds of the same dosage form produced by different manufacturers, the objective and accurate drawing of the dissolution curve and the comprehensive and in-depth study of the dissolution rate can be used to reveal that each manufacturer is producing The inherent quality of the time and the difference in the preparation process can also provide references for the level of bioavailability in the body and whether the organisms are equivalent.
Comparing the in vitro dissolution rates of glimepiride tablets and dripping pills, the test drug used glimepiride tablets with a specification of 1mg/tablet produced by company A, and glimepiride dripping pills with a specification of 1mg/tablet produced by company B. The reference substance is prepared by recrystallizing the glimepiride raw material provided by a certain company for 3 times. Methods Ultraviolet spectrophotometry was used to determine the content of glimepiride, and then the cumulative dissolution percentages of glimepiride tablets and dripping pills were calculated, and Weibull was used to determine the relevant parameters (r), shape parameters (m), and drug The time to release 63.2% (Td) and the time to release 50% of the drug (T50) were analyzed by fitting. Results The r, m, Td and T50 of dripping pills and glimepiride tablets were 0.988 6, 0.998 4, 1.161, 1.083, 9.03, 22.48, 6.59, 15.68, respectively. It was found that the dissolution rate of glimepiride tablets was slower than that of dripping pills.
Glimepiride is difficult to dissolve in water, so the main problem of this kind of drugs is how to increase the dissolution rate in vitro and improve the bioavailability. Generally, there is a big difference in in vitro dissolution between different dosage forms of the same drug. Dropping pills are liquid or solid drugs that are dissolved, emulsified or suspended in a matrix, and then dripped into the drug matrix. In the melted cooling liquid, it shrinks and condenses to become a partial or spherical pill. Compared with tablets, its curative effect is more rapid, reducing the particle size of the drug, increasing the area of diffusion, and improving the bioavailability.
The initial efficacy of glimepiride dripping pills is fast and the dissolution rate is high, which is conducive to the control of blood glucose after meals. Related substances are increasing rapidly, so attention should be paid to the influence of temperature and humidity on the drug in the production, storage, and transportation process and the area where it is used.
Some researchers have conducted a test on the short-term efficacy of glimepiride combined with metformin in the treatment of type 2 diabetes and its influence on neuropeptide Y (NPY), tumor necrosis factor-α (TNF-α) and other indicators. Methods Ninety patients with type 2 diabetes who were admitted to the Second Affiliated Hospital of Xi’an Medical College from February 2015 to February 2016 were selected as the research objects. The patients were randomly divided into group A and group B, with 45 cases in each group. Group A was treated with metformin, and group B was treated with glimepiride combined with metformin. Observe the fasting blood glucose (FPG), 2 h postprandial blood glucose (2 h PG), fasting insulin (FINS), and glycosylated hemoglobin (Hb A1c) before and after treatment. Levels, serum high-sensitivity C-reactive protein (hsCRP), TNF-α, interleukin-6 (IL-6), interleukin-8 (IL-8) levels and plasma NPY level changes, compare the clinical efficacy of the two groups And the occurrence of adverse reactions.
The results showed that the total effective rate of group B after treatment was 95.6% (43/45), which was significantly higher than that of group A’s 77.8% (35/45). The difference between the groups was statistically significant (P<0 . 05). After treatment, the levels of FPG, 2 h PG, FINS, Hb A1c, hs-CRP, TNF-α, IL-6 and IL-8 levels, and NPY levels of the two groups of patients were significantly improved compared with those before treatment, and the levels of group B The improvement was significantly better than that of group A (P <0.05). Therefore, glimepiride combined with metformin has a significant effect in the treatment of type 2 diabetes, which can significantly improve the levels of blood NPY, TNF-α and other indicators, and has small adverse reactions.
Glimepiride combined with saxagliptin can significantly reduce blood sugar in patients with type 2 diabetes
Some researchers have conducted clinical trials to explore the clinical effect and safety of glimepiride combined with saxagliptin in the treatment of type 2 diabetes. A total of 64 patients with type 2 diabetes who were admitted to the Shanghai Xuhui District Central Hospital from November 2016 to November 2017 were selected and randomly divided into a control group and a treatment group, with 32 cases in each group. In the control group, saxagliptin tablets were taken orally 0.5 h before breakfast, 5 mg/time, once daily. On the basis of the control group, the treatment group took orally glimepiride tablets 0.5 h before breakfast, the initial dose was 1 mg, and the maximum dose was no more than 6 mg/d, once a day. Both groups of patients were treated for 3 consecutive months. Observe the clinical efficacy of the two groups, and compare the fasting blood glucose (FBG), 2 h postprandial blood glucose (2 h PG), glycosylated hemoglobin (Hb A1c), fasting insulin (FINS), and insulin resistance index (HOMA-IR) of the two groups before and after treatment. ) And pancreatic β cell function index (HOMA-β) levels.
Results After treatment, the total effective rates of the control group and the treatment group were 84.38% and 96.88%, respectively, and the difference between the two groups was statistically significant (P<0.05). After treatment, the two groups of FBG, 2 h PG, Hb A1c, FINS, 2 h INS and HOMA-IR were significantly lower than before treatment, and HOMA-β was significantly higher than before treatment. The difference in the same group was statistically significant (P <0.05); and after treatment, the levels of these indicators in the treatment group were significantly better than those in the control group, and the difference between the two groups was statistically significant (P<0.05). Therefore, glimepiride combined with saxagliptin can significantly reduce blood sugar in patients with type 2 diabetes, improve insulin resistance and pancreatic β-cell function, without obvious adverse drug reactions.
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