Pharmacokinetic Properties of a New Controlled-Release Formulation of Carvedilol

Tenero, David M.; Henderson, Linda S.; Baidoo, Charlotte A.; Harter, Angela H.; Campanile, Andrea M.; Danoff, Theodore M.; Boyle, Duane

doi:10.1016/j.amjcard.2006.07.014

Cited by 27 publications

(28 citation statements)

References 13 publications

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“…This value is consistent with the proposed approximate 30% increase in the CR carvedilol free-base daily dose that was based on calculation of the CR exposure using the traditional noncompartmental analysis. 11 Carvedilol pharmacokinetics has shown consistent diurnal variability with lower rate of absorption and lower C max for the evening administration of IR carvedilol when compared with the morning administration. 11 Similar diurnal phenomenon was observed with the majority of the IR data analyzed in the present report.…”

Section: Discussionmentioning

confidence: 99%

“…11 Carvedilol pharmacokinetics has shown consistent diurnal variability with lower rate of absorption and lower C max for the evening administration of IR carvedilol when compared with the morning administration. 11 Similar diurnal phenomenon was observed with the majority of the IR data analyzed in the present report. Consequently, we assigned different bioavailability factors and absorption rate constants for the morning and evening doses since the difference cannot be regarded only as a consequence of the random variability of the study occasion.…”

Section: Discussionmentioning

confidence: 99%

“…11 The pharmacokinetics of the CR dosage form of carvedilol was evaluated and previously reported. 11 , 12 The CR dosage form has shown a prolonged release profi le as compared with the IR dosage form in healthy volunteers as well as in patients with hypertension and congestive heart failure.…”

Section: Introductionmentioning

confidence: 99%

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Population pharmacokinetics of S(−)-carvedilol in healthy volunteers after administration of the immediate-release (IR) and the new controlled-release (CR) dosage forms of the racemate

Othman

Tenero

Boyle

et al. 2007

AAPS J

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Carvedilol is a b 1 -, b 2 -, and a 1 -adrenoreceptor blocker indicated for treatment of hypertension and mild-tosevere congestive heart failure. The objective of this study was to develop and evaluate a single population model that describes S ( -)-carvedilol pharmacokinetics from both the immediate-release (IR) and the new controlledrelease dosage forms of the racemate. Carvedilol IR data (1270 measurements) were obtained from 2 open-label studies (50 mg/25 mg Q12 hours for 2 doses). Carvedilol CR data (2058 measurements) were obtained from an open-label, nonrandomized, dose-rising (10, 20, 40, and 80 mg), 4-period balanced crossover study. All data were simultaneously analyzed using NONMEM V. Leverage analysis and internal evaluations were conducted for the final model. A 2-compartment model with first-order absorption and elimination provided the best fi t. The model included different absorption rates (KAs) for the CR and IR morning (IR AM ) and evening (IR PM ) doses; incorporating change-points at certain times. Estimates of KAs indicated that the absorption was slower at equivalent times and extended for CR relative to IR carvedilol. Oral clearance of S ( -)-carvedilol was 149 L/h. The IR PM and the CR doses had bioavailability (F rel ) of 0.80 and 0.76, respectively, relative to the IR AM dose. The inter-subject variability in KAs was lower for the CR dosage form than the original IR dosage form. Estimation of interoccasion variability on KAs and F rel for the CR dosage form improved the fi t. The model performed well in simulation and leverage analysis indicated its robustness. The model will be a useful tool for future simulation studies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Population pharmacokinetics of S(−)-carvedilol in healthy volunteers after administration of the immediate-release (IR) and the new controlled-release (CR) dosage forms of the racemate

Othman

Tenero

Boyle

et al. 2007

AAPS J

Self Cite

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“…3 Conventional tablet dosage form of carvedilol is used to treat mild-to-moderate hypertension and angina pectoris. 4 Carvedilol is rapidly and extensively absorbed following oral administration, with an absolute bioavailability of approximately 25 to 35% due to a significant degree of first-pass metabolism. 5 The half-life of carvedilol is between 7 and 8 hours.…”

Section: Optimizationmentioning

confidence: 99%

Assessment of Once Daily Sustained Release Hydrophilic Matrix Tablet of Carvedilol

Kumar

Islam

Halder

et al. 2017

Dhaka Univ. J. Pharm. Sci

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ABSTRACT:The objective of the present study was to design and evaluate once daily sustained release tablet of carvedilol, using two molecular weight grades of hydrophilic polymers (methocel ® K4M CR and methocel ® K15M CR) as release retarding materials. Two sets of formulations were prepared, where first set of four formulations (F1-F4) contained variable ratios of methocel ® K4M CR and methocel ® K15M CR (15% : 15%, 15% : 13%, 15% : 11%and 15% : 9%) to optimize the composition of polymers in the tablet matrices such that the drug and polymer interaction was sufficient for sustaining release up to 24 hours and second set of five formulations (F5-F9) contained variable percentages of sodium lauryl sulfate (SLS) (1.0, 1.25, 1.5, 1.75 and 2.0%) to enhance the dissolution rate of the drug from the tablet matrices because of its poor aqueous solubility. The tablets were prepared by direct compression method and evaluated for hardness, thickness, friability, weight variation and in vitro drug release. The in vitro dissolution studies were carried out in simulated gastric fluid (900 ml, pH 1.2) for 24 hours using USP type II apparatus operated at 100 rpm and 37 ± 0.05°C. The release profiles were explored and explained by zero order, first order, Higuchi, Korsmeyer-Peppas and Hixson-Crowell models. From this study, the drug release profiles for formulations F6 to F9 were found to be satisfactory and the release mechanism followed both diffusion and erosion.Due to lower percentage of SLS used, F6 was considered as the best formulation.

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“…A once-daily, controlled-release (CR) formulation of carvedilol has been developed that provides levels of exposure similar to those achieved after administration of the current twice-daily formulation. Over a 24-hours period, carvedilol CR has been shown to maintain a steady plasma concentration time profile (Tenero et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Design and evaluation of Carvedilol nanocrystals sustained release tablets

2017

J App Pharma Sci

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The present study was undertaken to develop and evaluate the carvedilol nanocrystals sustained release (SR) tablets. The tablets were prepared by direct compression method using hydroxy propyl methyl cellulose (HPMC) and ethyl cellulose (EC) polymers. The prepared tablets were evaluated in terms of their precompression studies, post-compression parameters, in vitro dissolution and drug release kinetic. The tableting of blend showed good pre-compression properties and the formulated tablets were exhibited desired postcompression characters. The in vitro drug release were performed in the United States pharmacopoeia (USP) apparatus-II (Paddle) using phosphate buffer (pH 6.8). The formulation CT5 was selected as the optimized formulation by an in vitro drug release for 24 hrs with the release of 99.46%. Drug release kinetics showed the best fit to Higuchi's equation, and they exhibit diffusion dominated mechanism. The comparative in vitro release study showed that the formulation CT5 has better control over the release of drug (99.46%) when compare to reference product (73.64%) for 24 hrs. Thus overall result indicate that the carvedilol nanocrystal using SR tablets is more discriminative approach for better release and prolong action.

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Pharmacokinetic Properties of a New Controlled-Release Formulation of Carvedilol

Cited by 27 publications

References 13 publications

Population pharmacokinetics of S(−)-carvedilol in healthy volunteers after administration of the immediate-release (IR) and the new controlled-release (CR) dosage forms of the racemate

Population pharmacokinetics of S(−)-carvedilol in healthy volunteers after administration of the immediate-release (IR) and the new controlled-release (CR) dosage forms of the racemate

Assessment of Once Daily Sustained Release Hydrophilic Matrix Tablet of Carvedilol

Design and evaluation of Carvedilol nanocrystals sustained release tablets

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