Studies On Barnidipine Hydrochloride Self-microemulsifying Drug Delivery System

Barnidipine hydrochloride is a novel 1,4-dihydropyridine Ca2+ antagonist possessing potent antihypertensive activity. This drug stereospecifically binds to the binding sites of [3H] nitrendipine and [3H](+)PN200-110 in cardiac, brain and vascular tissues with high affinity. The bioavailability of Barnidipine in humans(3% to 4%) was less than or equal to that of other 1,4-dihydropyridine derivatives while the half-life (7.5h to 10.0h) was the same or longer.In order to improve the bioavailability of barnidipine, we develop the formulation of Barnidipine selfmicroemulsifying drug delivery system(BN-SMEDDS). In this paper, BN-SMEDDS can be formed quickly, significantly enhance the drug dissolution and gastrointestinal mucosal permeability, thereby enhancing the bioavailability of drugs, and reduce adverse reactions.First, the equilibrium solubility of barnidipine in different compositions of oils and emulsifiers was investigated.The compatible combination of oil, emulsifier and coemulsifier was determined. The best excipient were MCT,RH40 and Glycerine.The effects of oil,surfactant,cosurfactant,and the weight percentage of drug(BN) were then investigated. Central composite design-response surface methodology was utilized to optimize the ratio of these vehicles. The optimized formula for BN–SMEDDDS was Barnidipine,MCT,RH40, and glycerine,and the proportion of them was ( w∶w∶w∶w = 10∶329∶429∶232).In situ intestinal perfusion studies were consequently undertaken to assess the membrane perneability of BN-SMEDDS. The influence of bile flow,particle size were studied. The results showed that BN-SMEDDS had good membrance permeability; bile flow had little influence on absorption of BN.The absorption rate of the drug depends on the particle size of BN-SMEDDS, the smaller one is better.The mean particle size of the optimized formulation of BN-SMEDDS was 68.0 nm. The stability of BN-SMEDDS was good at room temperature with no obvious change of appearance, drug content, self-microemulsifying rate and partlcle size. The Pharmacokinetics test of BN in rats was performed by HPLC method. Data showed that BN-SMEDDS could increase bioavailability of BN significantly compared with BN suspension and the relative bioavailability was 205.1%.