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.
Gil
Eddy Castellanos
EC
Center of Pharmaceutical Chemistry, Calle 200 esq 21, Atabey, Playa, Havana, Cuba. eddy02cu@yahoo.es
Colarte
Antonio Iraizoz
AI
Bataille
Bernard
B
Pedraz
José Luis
JL
Rodríguez
Fernand
F
Heinämäki
Jyrki
J
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