Formulation Development and In-vitro Evaluation of Sustained Release Tablets of Metoprolol Succinate

Metoprolol succinate is a β1 selective antagonist used an anti-arrhythmic, antiagina, antihypertensive. sustained release tablet of metoprolol succinate were formulated using polymers. The half-life of drug is relatively 4-6 hours. The formulation of metoprolol succinate tablet were produced by direct compression or wet granulation method. The formulations were evaluated for thickness, hardness, weight variation, friability and dissolution, drug content all the physical characteristics of the formulated tablets were within acceptable limits. The dissolution studies of Metoprolol succinate sustained release tablets reflects USP specification NMT 25%by 1 hours, 20-40%by 4 hours,40-60%by 8 hours and more than 80% by 20 hrs.

Morpho-functional indicators changes of rats’ myocardium in experimental doxorubicin-induced chronic heart failure and its pharmacological modulation with new 4-amino-1,2,4-triazole derivative

Bromide 1 - (β-phenylethyl)-4-amino-1,2,4-triazolium (Hypertril) has the properties of a beta-blocker and of NO-mimetic, is assigned to the IV class of toxicity. All these effects make Hypertril a promising drug for the treatment of cardiovascular diseases. The aim of this paper was to study the cardioprotective action of Hypertril in terms of the effect on the morpho-functional parameters of the myocardium in rats with experimental chronic heart failure (CHF). CHF was modeled on 80 white outbred rats weighing 190–220g by administering doxorubicin at a cumulative dose of 15 mg/kg. Hypertril and the reference drug metoprolol succinate were administered within 30 days after CHF modeling, intragastrically at doses of 3.5 mg/kg and 15 mg/kg. Morphometric analysis of the cellular structure of the myocardium was carried out on an Axioskop microscope (Zeiss, Germany), in an automatic mode using a macro program developed in a specialized programming environment VIDAS-2.5 (Kontron Elektronik, Germany). The administration of Hypertril to animals with CHF led to an increase in the density of nuclei of cardiomyocytes, the area of myocardiocyte nuclei, an increase in the nuclear cytoplasmic ratio and an increase in the concentration of RNA in the nuclei and cytoplasm of cardiomyocytes compared with the group of untreated animals, which indicated the presence of a pronounced cardioprotective effect in the drug candidate. In terms of such indicators as the density of surviving cardiomyocytes and the content of RNA in them, the nuclear-cytoplasmic ratio of Hypertril is significantly (p < 0.05) superior to metoprolol.

Formulation and Development of Metoprolol Succinate Sustained Release Matrix tablet using Remusatia vivipara tubers mucilage

The purpose of this research was to formulate and evaluate sustained release tablet by using novel polymer Remusatia vivipara tubers mucilage. Currently natural gums and mucilages are being used extensively comparable to synthetic drug release modifiers. Natural plant materials possess various advantages. These are very cheap, biocompatible, biodegradable and free from side effects. In present research Metoprolol succinate matrix tablets were prepared by using Remusatia vivipara tubers mucilage. For the formulation of sustained release matrix tablets, direct compression method was used. The formulated matrix tablets were then evaluated for thickness, diameter, hardness, weight variation, friability, drug content, swelling index, in-vitro drug release and stability studies. The formulated sustained release tablet passed all tests required. The dissolution profile of prepared tablets showed sustained release of drug up to 11 hours compared to the reference tablet formulation PROLOMET XI 100. Drug release data were then fitted in to release kinetic models such as zero order kinetic, first order kinetic, Higuchi model and Korsmeyer-Peppas model to study the release pattern of drug from each formulation. The prepared sustained release tablet formulation was compared with marketed formulation (reference formulation) for drug release study and factor f1 (difference factor) and f2 (similarity factor) were determined. From this study it can be concluded that as the concentration of Remusatia vivipara mucilage increases, there is decrease in the rate of drug release from the formulation. The best formulation was found to be F3 which consists of 20% Remusatia vivipara mucilage but did not give comparable drug release profile to the reference formulation with factor f1 69.4 % and f2 34.8%. But it can be said that Remusatia vivipara gum mucilage can be used in tablet formulation to give sustained release effect up to 10 hours or in combination with other natural gum mucilage it may enhance the release retardant effect of drug up to or more than 20 hrs. The release kinetic study showed that the prepared sustained release tablet formulation shows anomalous (non-fickian) diffusion pattern and follows both diffusion controlled and swelling controlled mechanisms for drug release.

Perspective on the role of four beta-blockers in heart failure

Background: The current recommendations of the American College of Cardiology/American Heart Association and a previous Bayesian analysis clearly show a mortality benefit with the use of β- blockers in chronic HF, especially for bisoprolol, carvedilol, and sustained-release metoprolol succinate. Objective: The main objective was to report the evidence on the use of the afore-mentioned β-blockers in subjects with heart failure and to characterize the stages of heart failure in response to the four different β-blockers. Furthermore, it shed light on the patient’s satisfaction and improved quality of life using the afore-mentioned β-blockers in subjects with heart failure. Method: The current perspective presented the clinical outcomes, including hospitalization, morbidity, mortality, patient’s satisfaction, and quality of life, of four beta (β)-blockers, namely bisoprolol, carvedilol, metoprolol succinate, and nebivolol in different stages of heart failure. Results : The use of these three agents should be recommended for all stable subjects with current or previous symptoms of heart failure and heart failure with reduced ejection fraction unless there is any contraindication. The fore-mentioned β-blockers (bisoprolol, carvedilol, and metoprolol succinate) can be initiated early, even in stable and symptom-free (at rest) subjects with heart failure. β-blockers in heart failure should be commenced at small doses and then titrated upward as tolerated to achieve the desired clinical effects on heart rate and symptom control. Conclusion: Cardiologists should weigh the benefit-risk in subjects with heart failure and other co-existing cardiovascular problems such as atrial fibrillation and diabetes.

Development of a Scalable Process of Film-Coated bi-Layer Tablet Containing Sustained-Release Metoprolol Succinate and Immediate-Release Amlodipine Besylate

The development of new drugs that combine active ingredients for the treatment hypertension is critically essential owing to its offering advantages for both patients and manufacturers. In this study, for the first time, detailed development of a scalable process of film-coated bi-layer tablets containing sustained-release metoprolol succinate and immediate-release amlodipine besylate in a batch size of 10,000 tablets is reported. The processing parameters of the manufacturing process during dry mixing-, drying-, dry mixing- completion stages were systematically investigated, and the evaluation of the film-coated bi-layer tablet properties was well established. The optimal preparation conditions for metoprolol succinate layer were 6 min- dry mixing with a high-speed mixer (120 rpm and 1400 rpm), 30-min drying with a fluid bed dryer, and 5-min- mixing completion at 25 rpm. For the preparation of amlodipine besylate layer, the optimal dry-mixing time using a cube mixer (25 rpm) was found to be 5 min. The average weight of metoprolol succinate layers and bi-layer tablets were controlled at 240–260 mg and 384–416 mg, respectively. Shewhart R chart and X¯ charts of all three sampling lots were satisfactory, confirming that the present scalable process was stable and successful. This study confirms that the manufacturing process is reproducible, robust; and it yields a consistent product that meets specifications.