Preparation and in vitro release of ivabradine hydrochloride elementary osmotic pump tablets

In this study, ivabradine hydrochloride (IVB) was prepared as elementary osmotic pump tablets whose administration frequency was reduced to once daily. The dissolution method was developed, and effects on drug release profiles were evaluated by single factor analysis involving suspending agents, osmotic active agents and aging process. Orthogonal test was carried out at 3 levels on 3 factors including the amount of polyoxyethylene (PEO) in the core, polyethylene glycol (PEG) percentage and weight increase of controlled-release film coatings. The final formulation consisted of IVB (16.25 mg), PEO N80 (60 mg), hypromellose E5 (10 mg), lactose (111.75 mg), magnesium stearate (2 mg); and the film coatings consisted of PEG (15%), cellulose acetate (85%), with a weight increase of 7.5%. In vitro drug release behaviors were investigated. Prepared tablets exhibited similar release profiles in different pH dissolution media, with no risk of dose dumping in 40% ethanol solutions. The osmotic pressure differences inside and outside the membrane drove drug release. IVB osmotic pump tablets could reduce the frequency of administration and improve patients'' compliance, thus with better application values.