Preparation of a push-pull osmotic pump of felodipine solubilized by mesoporous silica nanoparticles with a core-shell structure.

The purpose of this study was to use mesoporous silica nanoparticles to improve drug dissolution after releasing from a push-pull osmotic pump. Felodipine was selected as the model drug and it was first incorporated into mesoporous silica nanoparticles prepared previously by the solvent evaporation method after we had examined a series of drug-silica ratios to load the drug into the mesoporous silica nanoparticles in order to find the optimum ratio for drug loading. Then, the drug-carrier was added to the drug-layer of the push-pull osmotic pump. PEO (Mw 100,000) was used as a suspending agent and PEO (Mw 6,000,000) was used as an expanding agent. The core tablets were coated with cellulose acetate (CA) as a semipermeable membrane containing polyethylene glycol (PEG) 6000 to control the membrane permeability. In vitro dissolution studies showed that the self-made osmotic pump tablets were able to deliver felodipine in an approximately zero-order manner in 12 h. A pharmacokinetic study was carried out to compare the new system with reference sustained-release tablets. It was found that the half-life of felodipine in the push-pull osmotic pump tablets was prolonged 1.8-fold, the bioavailability was increased 18% and the maximum plasma concentration reduced by 25%. In conclusion, using the self-made push-pull osmotic pump in combination with mesoporous silica nanoparticles was able to effectively increase the bioavailability of felodipine and reduce fluctuations in its plasma concentration.