New insights on how to adjust the release profile from coated pellets by varying the molecular weight of ethyl cellulose in the coating film
Artikel i vetenskaplig tidskrift, 2013

The major aims of this work were to study the effect of the molecular weight (Mw) of ethyl cellulose (EC) on the drug release profile from metoprolol succinate pellets coated with films comprising EC and hydroxypropyl cellulose (HPC) with a weight ratio of 70: 30, and to understand the mechanisms behind the different release profiles. A broad range of Mws was used, and the kinetics of drug release and HPC leaching followed. The higher the Mw of EC, the slower the HPC leaching and the drug release processes. Drug release occurred by diffusion through the pores created in the coating by the HPC leaching. A novel method was used to explain the differences in the release profiles: the effective diffusion coefficient (D-e) of the drug in the coating film was determined using a mechanistic model and compared to the amount of HPC leached. A linear dependence was found between D-e and the amount of HPC leached and, importantly, the value of the proportionality constant decreased with increasing Mw of EC. This suggests that the Mw of EC affects the drug release profile by affecting the phase separated microstructure of the coating and the hindrance it imparts to drug diffusion.

Diffusion

Mathematical modeling

Phase separation

Pellets

Ethyl cellulose

Molecular weight

Författare

M. Marucci

AstraZeneca Sweden

Helene Andersson

SuMo Biomaterials

Chalmers, Material- och tillverkningsteknik, Polymera material och kompositer

Johan Hjärtstam

AstraZeneca Sweden

Gary Stevenson

AstraZeneca Sweden

Julia Baderstedt

AstraZeneca Sweden

Mats Stading

Chalmers, Material- och tillverkningsteknik, Polymera material och kompositer

Anette Larsson

SuMo Biomaterials

Chalmers, Kemi- och bioteknik, Farmaceutisk teknologi

Christian von Corswant

AstraZeneca Sweden

International Journal of Pharmaceutics

0378-5173 (ISSN)

Vol. 458 218-23

Ämneskategorier

Annan kemi

Kemi

Styrkeområden

Materialvetenskap

DOI

10.1016/j.ijpharm.2013.09.016

PubMed

24076231