ABSTRACT
Food and formulation characteristics are crucial factors affecting the gastrointestinal release and absorption kinetics of oral solid preparations. In the present study, the dynamic continuous release and bioaccessibility of metformin hydrochloride immediate-release (IR) and sustained-release (SR) tablets were investigated in the dynamic human stomach-intestine (DHSI-IV) system simulating fasted and fed states in healthy adults. Both tablet formulations (particularly IR tablet) exhibited a postponed release in the fed state compared to the fasted state. Correspondingly, the bioaccessible fraction of metformin from IR tablets in the presence of high-fat meal was significantly reduced to 76.2 % of the fasted state. However, the in vitro bioaccessibility was less impaired by food for SR tablets with a fed/fasted ratio of 95.5 %. A convolution-based approach was used to convert in vitro bioaccessibility results to plasma concentration data. The predicted plasma concentration curve showed good agreement with human data in terms of pharmacokinetic (PK) parameters. In the fasted state, the predicted Cmax, Tmax and AUC0-24h of IR tablets were 943.9 ± 25.7 ng/mL, 2.0 ± 0.4 h and 7090.7 ± 112.0 ng.h/mL, respectively, mirroring values observed in healthy subjects. Overall, the DHSI-IV system has demonstrated potential to assess and predict the impact of meal intake on the in vivo release and absorption behaviors of oral solid preparations.
Subject(s)
Fasting , Metformin , Adult , Humans , Administration, Oral , Gastrointestinal Tract , Tablets , Delayed-Action Preparations/pharmacokinetics , Cross-Over Studies , Biological Availability , Area Under CurveABSTRACT
Objective To explore the effect of metformin hydrochloride tablets on the clinical efficacy, number of dominant follicles and ovarian volume of polycystic ovary syndrome. Methods 150 patients diagnosed with polycystic ovary syndrome who were diagnosed and treated in our hospital from January 2019 to March 2021 were selected .The patients were divided into observation group and control group by random number table. The control group was treated with letrozole + gonadotropin, and the observation group was treated with letrozole + gonadotropin + hydrochloric acid + Metformin tablets. The clinical efficacy, endometrial thickness, number of high-quality follicles, sex hormone levels, blood lipid levels, and adverse reactions were compared between the two groups. Results ① The effective rate of treatment in the observation group was 90.67%, which was significantly higher than that in the control group, 78.67% (P<0.05). ② After treatment, the endometrial thickness of the observation group was lower than that of the control group, and the number of high-quality follicles was more than that of the control group(P<0.05). ③ After treatment, the levels of Luteinizing Hormone-LH, Follicle Stimulating Hormone-FSH and Testosterone (T) in the observation group were lower than those in the control group (P<0.05). ④ After treatment, the total cholesterol (TC) and triglyceride (TG) in the observation group were lower than those in the control group (P<0.05). ⑤ The incidence of adverse reactions in the observation group was 8.00%, which was significantly lower than 20.00% in the control group (P<0.05). Conclusion Letrozole + gonadotropin + metformin hydrochloride tablets could significantly improve the sex hormone and blood lipid levels in patients with polycystic ovary syndrome, relieve the symptoms of the patients, and improve their uterine condition, which had a good clinical effect.
ABSTRACT
OBJECTIVE:To establish UV-spectrophotometry method in the determination of metformin hydrochloride in compound metformin hydrochloride tablets.METHODS:The determination was carried out with water as the solvent under the detection wavelength of233nm.RESULTS:There was a good linear relationship between metformin hydrochloride and its absorbability(r=0.9999)within the concentration range of1～10?g/ml.The average recovery was99.3%with RSD at0.24%(n=9).CONCLUSION:The method is accurate,fast,convenient,and which can be used to determine the contents of metformin hydrochloride in compound metformin hydrochloride tablets directly without isolation.
