Conventional Propranolol Research Articles

Design and evaluation of sustained-release and buccal adhesive propranolol hydrochloride tablets

The release of propranolol hydrochloride incorporated into sustained-release and buccal adhesive tablets was studied in vitro. The formulation containing 20% hydroxypropyl methylcellulose (HPMC) yielded good sustained-release matrix tablets. Buccal adhesive controlled-release tablets were prepared by compression of HPMC with polycarbophil (PAA), which served as the bioactive adhesive compound. The release behaviour of buccal adhesive tablets was found to be non-Fickian. The adhesion force was significantly affected by the mixing ratio of HPMC and PAA in the tablet and the weakest adhesion force was observed at the ratio of 1:1 (HPMC:PAA). Interpolymer complex formation was confirmed between HPMC and PAA in acidic medium by turbidity, viscosity and FT-IR measurements. The kinetics of sustained-release and buccal adhesive tablets of propranolol were examined in nine healthy volunteers. Conventional propranolol (Dideral®) was also studied for comparison purposes. As compared to conventional propranolol (40 mg), a single dose of 20% HPMC (160 mg) produced a smoother plasma level profile, with lower and delayed peak times. Dose corrected AUC 0–8 values were greater after Dideral® than after 20% HPMC (168.7 ± 80.3 vs 97.3 ± 36.1 ng h ml −1 p < 0.05). The buccal delivery of propranolol caused ulceration and serious irritation that took weeks to heal. There was no significant difference ( p > 0.05) in the AUC 0–4 values between 20% HPMC and buccal adhesive tablets.

Decreased Absorption as a Possible Cause for the Lower Bioavailability of a Sustained-Release Propranolol

The influence of sustained absorption on the oral availability of propranolol (P) and the metabolic disposition of P were investigated by obtaining the partial metabolic clearances (CLm) following long-acting P (LA) dosing in comparison with the conventional propranolol tablet (CP). Ten healthy volunteers were given a single oral dose of an LA capsule (60 mg) and CP (20 mg × 3) using a crossover design. Blood and urine samples were collected over 24- and 48-h postdose periods, respectively. Concentrations of P, propranolol glucuronide (PG), 4-hydroxypropranolol (4P), 4-hydroxypropranolol glucuronide (4PG), 4-hydroxypropranolol sulfate (4PS), and naphthoxylactic acid (NLA) were determined by HPLC with fluorescence and UV detection. Significant differences were observed between LA and CP in the area under the plasma concentration–time curves (AUCs) for P, PG, and NLA and in the amounts excreted into urine (Ae) for all measured metabolites (i.e., PG, 4P, 4PG, 4PS, and NLA). The parallel decrease of the AUC for P and the excreted amounts of all measured metabolites following LA dosing resulted in partial metabolic clearances (CLm) and renal clearances (CLr) for P and its metabolic that were similar to those observed for CP. Therefore, the hepatic metabolism of P would not be affected by the slower absorption at a single oral dose of 60 mg. These results indicate that the poor absorption of P from the gastrointestinal tract might be one of the factors causing the low bioavailability of P observed after administration of the sustained-release formulation.

Propranolol in the Prevention of First Upper Gastrointestinal Tract Hemorrhage in Patients with Cirrhosis of the Liver and Esophageal Varices

We conducted a prospective, randomized, multicenter, single-blind trial of propranolol as compared with placebo in the prevention of first upper gastrointestinal tract bleeding in patients with cirrhosis of the liver. A total of 230 patients (90 percent with alcoholism and 46 percent with a Child-Pugh grade C classification) with large esophageal varices without previous bleeding were randomly assigned to receive either propranolol (n = 118) or placebo (n = 112), after they had been divided into two groups according to the severity of their liver disease. The end points of the study were bleeding and death. The dose of propranolol was progressively increased to decrease the heart rate by 20 to 25 percent. The final doses were 40 mg of conventional propranolol and 160 and 320 mg of long-acting propranolol daily in 22 percent, 60 percent, and 18 percent of patients, respectively. The mean (+/- SD) follow-up time among survivors without bleeding was 436 +/- 172 days. The cumulative percentages of patients free of bleeding two years after inclusion in the study were 74 percent (95 percent confidence limits, 61 and 83) in the propranolol group and 39 percent (95 percent confidence limits, 15 and 69) in the placebo group (P less than 0.05). Cumulative two-year survival was 72 percent (95 percent confidence limits, 60 and 81) in the propranolol group and 51 percent (95 percent confidence limits, 37 and 64) in the placebo group (P less than 0.05). The advantage of propranolol over placebo was maintained when potentially confounding variables were adjusted with use of the Cox model. Side effects occurred in 17 percent of the patients who received propranolol and led to the stopping of treatment in 11 percent. We conclude that propranolol can decrease the incidence of first bleeding and death during a period of two years in patients with cirrhosis and large varices.

Comparison of a Long-Acting Form of Propranolol and Conventional Propranolol in the Treatment of Hypertension in Elderly Patients

Nineteen elderly hypertensive patients already being treated with a diuretic and, where necessary, another anti-hypertensive agent, were studied in a double-blind, randomized, crossover comparison of conventional propranolol, 40 mg three times daily, with a long-acting propranolol formulation, 160 mg once daily, as a second line agent. Patients were assessed before taking the morning's allocated medication. This was done as near as possible to 24 h after the last dose of once daily propranolol and as near as possible to 15 h after the last dose of three times daily conventional propranolol. Assessment was carried out at the time of randomization and after 4 weeks' treatment with both propranolol formulations. Heart rate and blood pressures were measured in the supine and standing positions and after exercise. Both propranolol formulations were effective as second line agents in these elderly patients and both were well tolerated. Patient compliance on both propranolol formulations was very good although the long-acting formulation may be of value in improving this still further.

Stable oral availability of sustained release propranolol when co‐ administered with hydralazine or food: evidence implicating substrate delivery rate as a determinant of presystemic drug interactions.

A study was made of the influence of hydralazine on the oral availability of a sustained release formulation of propranolol (Inderal LA). Sustained release propranolol 160 mg was given orally either alone or in combination with oral hydralazine 25 mg on separate occasions to six healthy volunteers. Blood and urine samples were collected post-dosing over 34 h. Peak concentrations of propranolol, time to peak and area under the plasma concentration-time curve (AUC) were not altered by co-administration of hydralazine with sustained release propranolol. Similarly, there was no change in recovery of 11C-labelled propranolol and metabolites in those individuals to whom tracer label was given. These results contrast with previous reports of marked interaction between the conventional formulation of propranolol and hydralazine or food. Interactions were confirmed between hydralazine and conventional propranolol in three subjects who had been studied previously with sustained release propranolol. Analysis of metabolite profiles in one of these subjects established that the major metabolites do change under hydralazine stimulus. These results indicate that substrate delivery rates may determine presystemic drug interactions, suggesting capacity limitations of hydroxylation processes or short-term flow redistribution following hydralazine, resulting in functional shunting past the hydroxylation enzymes. These results exclude global or lasting enzyme inhibition by hydralazine or simple flow-sensitivity of presystemic clearance.

Comparative oral bioavailability of conventional propranolol tablets and a new controlled-absorption propranolol capsule

AbstractThe relative bioavailabilities of a new once-a-day propranolol formulation (Duranol) and conventional propranolol tablets (Inderal) were evaluated in six healthy male volunteers in a randomized balanced cross-over study. During the first treatment period, subjects were administered either a single 160 mg Duranol capsule at 9 a.m. or 80 mg Inderal at 9 a.m. and 9 p.m. Plasma propranolol concentrations were measured at 0, 2, 3, 4, 5, 6, 8, 10, 12, 13, 14, 15, 16, 24 and 36 hours after the 9 a.m. dose.Mean peak plasma propranolol concentrations (Cmax) of 92.7 ng/ml at 2 hours and 53.9 ng/ml at 2.8 hours were recorded after administration of the first and second Inderal doses, respectively. After Duranol dosing, the Cmax of 85 ng/ml was not significantly different than the Inderal values; however, Duranol's tmax of 8 hours was significantly greater (p < 0.05) than either tmax recorded for Inderal. Compared to data obtained after administration of conventional propranolol tablets, mean propranolol conc...

The use of long-acting propranolol ('Inderal' LA) in the management of elderly hypertensive patients.

Fifteen elderly patients whose hypertension was controlled by conventional propranolol 80 mg twice a day had their medication changed to one capsule of 'Inderal' LA (160 mg) daily. The blood pressure, heart rate and propranolol concentrations were measured at various time points when the patients were receiving the conventional preparation and these assessments were repeated when the long-acting preparation was administered. Although the heart rate was lower with conventional propranolol than with 'Inderal' LA there was no significant difference in the blood pressure levels. The mean peak blood level of propranolol was, however, significantly lower with 'Inderal' LA compared with conventional propranolol and occurred later. At 12 h the plasma propranolol levels were higher after 'Inderal' LA then following the intake of conventional propranolol (p less than 0.01); there was no difference in the plasma levels at 24 h. The area under the concentration time curve was significantly higher on conventional propranolol. Compared with published data, the plasma levels were higher than those in younger patients. 'Inderal' LA was well tolerated and side effects were minimal.

Comparative Efficacy of Three Long-Acting β-Receptor-Blocking Agents against Conventional Propranolol: β-Receptor Blockade in the 24Th Hour after a Single Dose

Comparative Efficacy of Three Long-Acting <i>β</i>-Receptor-Blocking Agents against Conventional Propranolol: <i>β</i>-Receptor Blockade in the 24Th Hour after a Single Dose

Comparison of a Once Daily Long-Acting Formulation of Propranolol with Conventional Propranolol Given Twice Daily in Patients with Mild to Moderate Hypertension

The effect of conventional propranolol tablets given twice daily has been compared with an equivalent dosage of a long-acting formulation of propranolol ('Inderal' LA)p given once daily in twenty-nine patients with mild to moderate hypertension. The study lasted 10 weeks. There was no significant difference in clinical response to the two treatments which were equally effective and well tolerated. A once daily dosage schedule should greatly aid patient compliance.