EVALUATION OF DIFFERENT SYNTHETIC AND NATURAL POLYMERS AS PROTECTIVE LAYER ON HIGHLY SOLUBLE AND HIGH DOSE DRUG METOPROLOL SUCCINATEFOR MANUFACTURING OF CONTROL RELEASE MULTI UNIT PELLETS TABLETS

Objective: Evaluation of different natural and synthetic polymers as protective layer (PL) in the manufacturing of control release (CR) multi-unit pellets (MUPS) tablets, highly soluble and high dose drug metoprolol succinate (MS) was selected as model drug. The function of PL is to protect CR functional coating layer of pellets from damage during compression of MUPS tablets. Methods: MS is highly soluble biopharmaceutics classification system(BCS) Class–I molecule, hence selected aqueous solution layering method for drug loading in fluid bed processor (FBP), optimized formulation was manufactured by using seal coating on microcrystalline cellulose (MCC) pellets followed by drug loading (DL) and CR coating, applied by using the solution layering method in FBP. Given coating on these functional coated pellets with different natural and synthetic polymers like hydroxypropyl cellulose (Klucel LF), polyethylene glycol 6000 (PEG 6000), hypromellose 5 cps (HPMC 5cps), guar gum (GG) and xanthan gum (XM). Evaluated these pellet's for physical characterization and chemical characterization.Results: Drug release profiles of CR MUPS tablets containing PL coating were compared to those CR pellets and f2 values observed was 81.83, 49.92, 89.35, 66.44, and 85.25 with Klucel LF, PEG 6000, HPMC 5 cps, GG and XM coated MUPS tablets respectively. The dissolution data indicated that, there was no significant change were observed with MUPS containing Klucel LF, HPMC 5 cps, GG and XG PLs whereas faster release profiles were observed with PEG 6000PL MUPS tablets.Conclusion: Based on these dissolution profiles it was concluded that by applying low viscous natural or synthetic binders like Klucel LF, HPMC 5 cps, GG and XG on functional coating pellets given good protection to functional coating pellets from damage during compression. It is a very effective and potent strategy for manufacturing of MUPS tablets. Whereas PEG 6000 polymer not able to give protection to functional coating pellets from damage during compression, it may be due to its very low viscosity of PEG 6000

Health-status outcomes with invasive or conservative care in coronary disease

BACKGROUND In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients. METHODS We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency. RESULTS At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina). CONCLUSIONS In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline

Initial invasive or conservative strategy for stable coronary disease

BACKGROUND Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, 121.8 percentage points; 95% CI, 124.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used