Acta Pharm. 66 (2016) 173-189

 

full paper

Original research paper

 

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

ANDREEA LOREDANA VONICA-GLIGOR, IOAN TOMUȚĂ and SORIN E. LEUCUȚA

tomutaioan@umfcluj.ro

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

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

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

Accepted February 23, 2016

Published online April 8, 2016

 

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.

 

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