ВПЛИВ РОЗМІРУ ПОР ТА МОРФОЛОГІЇ МЕЗОПОРИСТОГО КРЕМНІЮ НА ВИВІЛЬНЕННЯ МЕТОПРОЛОЛУ ТАРТРАТУ

Purpose. Study pore size effect and morphology of mesoporous silica on metoprolol tartrate release.Methodology. A sample of hollow mesoporous silicon dioxide with amino-functional groups containing 12.7 wt. % metoprolol tartrate has been investigated as potential carriers for the controlled release of active substance. Studies of the release profiles of metoprolol tartrate were performed under the following conditions: dissolution medium was buffer solution with a pH of 7.4 (phosphate buffer); sampling time: from 0.5 h before 18 h. The metoprolol concentration in the liquid phase was evaluated by a UV-Vis spectrophotometer (Persee TU-190, Beijing, China) by use of quartz cuvettes with an optical path length of 1 cm at a maximum wavelength of 274 nm.Findings. In this work we have studied mesoporous silica as possible carrier to controlled release of metoprolol tartrate, a drug used in the treatment of some diseases of the cardiovascular system. The material for research was a sample of hollow mesoporous silicon dioxide with amino-functional groups 200–400 nm in size and 20–30 nm in shell thickness. A calibrated curve to determine the amount of metoprolol was constructed by determining the absorption dependence of the concentration of metoprolol in the range from 10 to 300 ppm. The same drug concentration was obtained as calculated from the drug release test formula, which concludes that the release of metoprolol is controlled.Originality. The controlled release of a sample of hollow spheres of mesoporous silicon dioxide filled with metoprolol tartrate was studied, which was synthesized by the School of Chemistry and Chemical Engineering, Qilu University of Technology, using a new technology, where hollow spheres of mesoporous silicon dioxide with amino groups were synthesized using CO2 gas bubbles as templates.Practical value. The metoprolol release amount could achieve a 50% release amounts within 1 hour and 90% within 5 hours, indicating that the synthesized mesoporous hollow sphere could achieve controlled drug release, and shows the potential of carriers with stimulus response and targeted therapy.

Evaluation of Clinical Efficiency of Cardioprotective Therapy in Patients with Acute Myocardial Infarction

Aim. To evaluate the efficiency of cardioprotective therapy using intravenous metoprolol in combination with a high dose of atorvastatin in the prevention of myocardial remodeling (MR) and heart failure (HF) in patients with acute ST-segment elevation myocardial infarction (STEMI).Material AND methods. A prospective study included 100 STEMI patients who underwent primary percutaneous intervention (PCI). Depending on the regimens of drug cardioprotection, three groups of patients were formed: the first (2014–2015) — 34 patients who received 80 mg atorvastatin as a part of the basic therapy on the first day of STEMI, then 20–40 mg/day for 30 days. The second group (2017–2018) — 34 patients who received atorvastatin 80 mg/day for a month from the onset of STEMI. The third group (2018–2019) — 32 patients who received intravenous metoprolol tartrate (5–15 mg) and atorvastatin 80 mg/day before PCI for a month from the onset of STEMI. On days 1 and 2 of STEMI and one month later, patients were assessed for serum levels of cardiac biomarkers; on the 1st, 7th days and one month later, echocardiographic studies (EchoCG) were performed. At the end of the observation, clinical and imaging outcomes (MR and HF) were assessed, which were compared with the dynamics of biomarkers between the groups of patients.Results. The combined use of atorvastatin 80 mg/day for a month from the onset of STEMI and a single intravenous injection of metoprolol tartrate (5–15 mg) in the acute phase of STEMI before PCI showed the most significant effects in the prevention of the development of structural and functional myocardial disorders and clinically severe heart failure, and also caused the minimal serum activity of cardiomarkers in the third group of patients in comparison with the first and second groups of patients without this drug combination. Also, correlations between biomarkers and echocardiography indicators were established in the third group of patients who received cardioprotective therapy.Conclusion. The combined use of high-dose atorvastatin for a month with a single intravenous injection of metoprolol tartrate in acute STEMI before PCI prevents the formation of MR and clinically significant HF in the post-infarction period. Comprehensive dynamic assessment of cardiac biomarkers and echocardiography parameters within a month after post-STEMI is a highly informative tools for monitoring the efficiency of cardioprotective therapy.

Heat Treatment Induced Specified Aggregation Morphology of Metoprolol Tartrate in Poly(ε-caprolactone) Matrix and the Drug Release Variation

Hot-melt blending has been widely used in the pharmaceutical industry to produce drug delivery systems, however, realizing the controlled drug release behavior of a hot-melt blended medicament it is still a tough challenge. In this study, we developed a simple and effective heat treatment method to adjust the drug release behavior, without the addition of any release modifiers. Thin metoprolol tartrate (MPT)/poly(ε-caprolactone) (PCL) tablets were prepared through hot-melt processing, and different morphologies of MPT were obtained by altering processing temperatures and the following heat treatment. MPT particles with different particle sizes were obtained under different processing temperatures, and fibrous crystals of MPT were fabricated during the following heat treatment. Different morphological structures of MPT adjusted the drug diffusion channel when immersed in phosphate-buffered saline (PBS), and various drug release behaviors were approached. After being immersed for 24 h, 7% of the MPT was released from the blend processed at 130 °C, while more than 95% of the MPT were released after the following heat treatment of the same sample. Thus, flexible drug release behaviors were achieved using this simple and effective processing manufacture, which is demonstrated to be of profound importance for biomedical applications.