Development and optimization of a novel sustained-release dextran tablet formulation for propranolol hydrochloride

Eddy Castellanos Gil , Antonio Iraizoz Colarte , Bernard Bataille , José Luis Pedraz , Fernand Rodriguez (1) , Jyrki Heinämäki

1 CIRIMAT - Centre interuniversitaire de recherche et d'ingenierie des matériaux

A novel oral controlled delivery system for propranolol hydrochloride (PPL) was developed and optimized. The in vitro dissolution profiles of sustained-release matrix tablets of racemic PPL were determined and compared with the United States Pharmacopeia (USP) tolerance specifications for Propranolol Hydrochloride Extended-Release Capsules. The influence of matrix forming agents (native dextran, hydroxypropyl methylcellulose (HPMC), cetyl alcohol) and binary mixtures of them on PPL release in vitro was investigated. A central composite design was applied to the optimization of a sustained-release tablet formulation. The sustained-release matrix tablets with good physical, mechanical and technological properties were obtained with a matrix excipient:PPL ratio of 60:40 (w/w), with a dextran:HPMC ratio of 4:1 (w/w) and with a cetyl alcohol amount of 15% (w/w). A comparative kinetic study of the present matrix tablets and commercial SUMIAL RETARD capsules (Spain) was established. The value for the similarity factor (f2 = 69.6) suggested that the dissolution profile of the present two sustained-release oral dosage forms are similar. Higuchi (diffusion) and Hixon–Crowell (erosion) kinetic profiles were achieved and this codependent mechanism of drug release was established.

Mots clés: Native dextran; Sustained release; Optimization; Propranolol; Tablets

Domaines: Matériaux

Eddy Castellanos Gil, Antonio Iraizoz Colarte, Bernard Bataille, José Luis Pedraz, Fernand Rodriguez, et al.. Development and optimization of a novel sustained-release dextran tablet formulation for propranolol hydrochloride. International Journal of Pharmaceutics, 2006, 317 (1), pp.32-39. ⟨10.1016/j.ijpharm.2006.02.049⟩. ⟨hal-03595642⟩