|
KMID : 0613820230330030268
|
|
Journal of Life Science
2023 Volume.33 No. 3 p.268 ~ p.276
|
|
|
Formulation Optimization Study of Carvedilol and Ivabradine Fixed-dose Combination Tablet Using Full-factorial Design
|
|
Song Yu-Lim
Kim Kang-Min
|
|
|
Abstract
|
|
|
|
This study was conducted to optimize the formulation conditions of the immediate-release layer of carvedilol in the development of a two-layer tablet formulation for carvedilol and ivabradine. Using a 24+3 full-factorial design of experiments, excipients (microcrystalline cellulose, citric acid, and crospovidone) of the carvedilol immediate-release layer (wet granulation part) and process parameters for the tablet compression process (main compression) were optimized, and seven types of each dependent variable (assay, content uniformity, hardness, friability, disintegration, and dissolution [pH 1.2 and 6.8]) were evaluated using design expert software. The analysis of variance results confirmed that the main compression has a significant effect on hardness, friability, and disintegration time and that microcrystalline cellulose has a major effect on friability and dissolution. In addition, it was confirmed that citric acid has a significant effect on friability. Crospovidone affects friability and dissolution. According to the design space from the design of the experiment results, the optimized range is microcrystalline cellulose (~18.0－32.0 mg), citric acid (~0.5－12 mg), and main compression (~615－837 kgf). Consequently, this study confirmed the availability of manufacturing the carvedilol immediate-release layer in which all risk factors evaluated in the initial risk assessment are removed.
|
|
|
KEYWORD
|
|
|
Bi-layer tablet, carvedilol, full-factorial design, ivabradine, two-layer tablet
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|
|