<abstract xmlns="http://www.w3.org/1999/xhtml"><p>The aim of this work was to develop a pulsatile release system with metoprolol for chronotherapeutical use by coating swellable mini-tablets with Eudragit RS. To study the influence of the formulation factors (amount of coating polymer, plasticizer percentage in film coating and swelling agent percentage in mini-tablets), a Box-Behnken design of experiment (DoE) was used. To evaluate the influence of the studied factors on the sigmoid shape of the dissolution profile, piecewise function parameters were used as the responses of DoE. The results show that higher concentrations of coating polymer and higher concentrations of plasticizer polymer led to a thicker and more elastic polymeric film, which led to a delay in drug release. Using the parameters of the piecewise function as DoE responses, an optimum formulation with a sigmoid shape dissolution profile and a 2.5-h lag time followed by rapid drug release were obtained.</p></abstract>

The aim of this work was to develop a pulsatile release system with metoprolol for chronotherapeutical use by coating swellable mini-tablets with Eudragit RS. To study the influence of the formulation factors (amount of coating polymer, plasticizer percentage in film coating and swelling agent percentage in mini-tablets), a Box-Behnken design of experiment (DoE) was used. To evaluate the influence of the studied factors on the sigmoid shape of the dissolution profile, piecewise function parameters were used as the responses of DoE. The results show that higher concentrations of coating polymer and higher concentrations of plasticizer polymer led to a thicker and more elastic polymeric film, which led to a delay in drug release. Using the parameters of the piecewise function as DoE responses, an optimum formulation with a sigmoid shape dissolution profile and a 2.5-h lag time followed by rapid drug release were obtained.

Piecewise function parameters as responses of the design of experiment in the development of a pulsatile release chronopharmaceutical system

Department of Pharmaceutical, Technology and Biopharmacy, Faculty of Pharmacy University of Medicine and Pharmacy, “Iuliu Haţieganu”, 40012 – Cluj-Napoca, Romania

S.C. Polisno Pharmaceuticals S.R.L., 550201 – Sibiu, Romania

Faculty of Medicine, “Lucian Blaga”, University of Sibiu, 550169 – Sibiu, Romania

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

The aim of this work was to develop a pulsatile release system with metoprolol for chronotherapeutical use by coating swellable mini-tablets with Eudragit RS....

Piecewise function parameters as responses of the design of experiment in the development of a pulsatile release chronopharmaceutical system

Published Online: May 28, 2016

Page range: 173 - 189

Accepted: Feb 23, 2016

DOI: https://doi.org/10.1515/acph-2016-0025

Keywords
pulsatile release, chronopharmaceutical system, piecewise function, design of experiment, Eudragit RS, metoprolol

© 2016 Andreea Loredana Vonica-Gligor et al., published by De Gruyter Open

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Piecewise function parameters as responses of the design of experiment in the development of a pulsatile release chronopharmaceutical system

Published Online: May 28, 2016

Page range: 173 - 189

Accepted: Feb 23, 2016

DOI: https://doi.org/10.1515/acph-2016-0025

Keywordspulsatile release, chronopharmaceutical system, piecewise function, design of experiment, Eudragit RS, metoprolol

© 2016 Andreea Loredana Vonica-Gligor et al., published by De Gruyter Open

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Keywords
pulsatile release, chronopharmaceutical system, piecewise function, design of experiment, Eudragit RS, metoprolol