Development and optimization of a novel sustained-release dextran tablet formulation for propranolol hydrochloride.
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 (f(2)=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.
Center of Pharmaceutical Chemistry, Calle 200 esq 21, Atabey, Playa, Havana, Cuba. eddy02cu@yahoo.es
Eddy Castellanos
EC
Gil
Antonio Iraizoz
AI
Colarte
Bernard
B
Bataille
José Luis
JL
Pedraz
Fernand
F
Rodríguez
Jyrki
J
Heinämäki
D002214:Capsules; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D003911:Dextrans / Q000737:chemistry*; D005233:Fatty Alcohols / Q000737:chemistry; D006244:Hardness; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D011433:Propranolol / Q000737:chemistry*; D012995:Solubility; D013607:Tablets
D002214:Capsules; D003692:Delayed-Action Preparations; D003911:Dextrans; D005233:Fatty Alcohols; D013607:Tablets; D065347:Hypromellose Derivatives; D008747:Methylcellulose; C005031:cetyl alcohol; D011433:Propranolol; D002266:Carboxymethylcellulose Sodium