Nisoldipine Infiltration Pump Controlled Release Formulations

In this paper, nisoldipine was selected as the model drug to prepare bi-layer osmotic pump tablets(BOPT) and mono-layer osmotic pump tablets(MOPT). And the drug release character and mechanism were studied. At last, the relative bioavailability and pharmacokinetic study of nisoldipine bi-layer osmotic pump tablets were performed.In the preparation of BOPT , Polyethylene oxide (PEO),sodium chloride, polyvinylpyrrolidone K-29/32 (PVP K-29/32), and hydroxypropyl methylcelluse(HPMC) were used to make the tablet core. Cellulose acetate (CA) and polyethylene glycol 400 (PEG400) were selected as the coating materials and acetone solvent was employed as the coating medium. The effects of many factors including formulation of drug layer, push layer and coating membrane, hardness of tablet core and the condition of drug release on the release behavior of BOPT were investigated. Based on the comprehensive single-factor experiments, amount of NaCl, PEO in the push layer and coating thickness were selected as the causal factors, similarity factors (f2) between the in vitro accumulative drug release amount of self-prepared tablets and imported sustained tablets(Sular, Bayer) was used as the evaluation standard to optimize the formulations according to orthogonal experiment design. The results indicated that the optimal formulation had the excellent zero-order release character as well as Sular. The investigation of the mechanism of the in vitro drug release showed that the main power of drug release was the difference of osmotic pressure between the tablet core and the dissolution medium during drug release.In order to settle the so called time-lag and simplify the producing process of BOPT, nisoldipine MOPT was also studied. The effects of polymer, osmotic pressure promoting agent, drug loading, PEG400 content in the...