TY - JOUR

T1 - Mathematical modeling of drug release from Eudragit RS-based delivery systems

AU - Glaessl, B.

AU - Siepmann, F.

AU - Tucker, I.

AU - Rades, T.

AU - Siepmann, J.

N1 - Funding Information: The authors are grateful for the support of this work by the Nord-Pas-de-Calais Regional Council (Interdisciplinary Research Center on Drug Products, PRIM: “Pôle de recherche interdisciplinaire pour le médicament”).

PY - 2010

Y1 - 2010

N2 - Various types of tartaric acid, metoprolol free base and metoprolol tartrate containing Eudragit RS-based films were prepared and physicochemically characterized. In particular, the water uptake and compound release kinetics were monitored upon exposure to 0.1 M HCl, phosphate buffer pH 7.4 and distilled water. Appropriate analytical solutions of Fick's second law of diffusion, considering the given initial and boundary conditions, were used to elucidate the underlying mass transport mechanisms. Furthermore, the apparent diffusion coefficients of water, tartaric acid, metoprolol free base and metoprolol tartrate in the different Eudragit RS-based networks were determined. Importantly, the diffusivity of metoprolol tartrate and metoprolol free base significantly increased with increasing initial drug content, illustrating the strong plasticizing capacity of these compounds for the polymer. In contrast to Eudragit RL-based films, metoprolol free base precipitation occurred only at higher initial drug loadings, due to the lower water uptake resulting from the lower contents of quaternary ammonium groups. Interestingly, negatively charged tartrate ions diffused out more rapidly from metoprolol tartrate containing films than positively charged metoprolol ions, indicating that the lower molecular weight over-compensates the attractive ionic interactions with the positively charged macromolecules.

AB - Various types of tartaric acid, metoprolol free base and metoprolol tartrate containing Eudragit RS-based films were prepared and physicochemically characterized. In particular, the water uptake and compound release kinetics were monitored upon exposure to 0.1 M HCl, phosphate buffer pH 7.4 and distilled water. Appropriate analytical solutions of Fick's second law of diffusion, considering the given initial and boundary conditions, were used to elucidate the underlying mass transport mechanisms. Furthermore, the apparent diffusion coefficients of water, tartaric acid, metoprolol free base and metoprolol tartrate in the different Eudragit RS-based networks were determined. Importantly, the diffusivity of metoprolol tartrate and metoprolol free base significantly increased with increasing initial drug content, illustrating the strong plasticizing capacity of these compounds for the polymer. In contrast to Eudragit RL-based films, metoprolol free base precipitation occurred only at higher initial drug loadings, due to the lower water uptake resulting from the lower contents of quaternary ammonium groups. Interestingly, negatively charged tartrate ions diffused out more rapidly from metoprolol tartrate containing films than positively charged metoprolol ions, indicating that the lower molecular weight over-compensates the attractive ionic interactions with the positively charged macromolecules.

KW - Controlled release

KW - Diffusion

KW - Drug polymer interactions

KW - Eudragit RS

KW - Mathematical modeling

UR - http://www.scopus.com/inward/record.url?scp=77950618402&partnerID=8YFLogxK

U2 - 10.1016/S1773-2247(10)50017-0

DO - 10.1016/S1773-2247(10)50017-0

M3 - Journal article

AN - SCOPUS:77950618402

VL - 20

SP - 127

EP - 133

JO - Journal of Drug Delivery Science and Technology

JF - Journal of Drug Delivery Science and Technology

SN - 1773-2247

IS - 2

ER -