Study On Preparation And Pharmacokinetics Of Nifedipine-loaded Solid Lipid Nanoparticles.

Objective: To produce nifedipine-loaded Solid Lipid Nanoparticles (NP-SLN) and its transdermal delivery system. To study the NP-SLN and its preparation by pharmacokinetic method in vivo, in order to evaluate the potential application of the agent.Methods: In this paper, cetylpalmitate was used as a carrier material to prepare nifedipine-loaded solid lipid nanoparticles. A series of experiments based on even design had been done to screen and optimize the manufacture condition. The preparation of NP-SLN was performed by hot high pressure homogenization(HPH) technic. Both photon correlation spectrum(PCS) and laser diffusion(LD) were used to determine the particle size and distribution. The stabilization of the NP-SLN and its transdermal agent were determined within certain time. Drug content of NP-SLN was assayed by ultraviolet spectrophotometer. Rabbit plasma concentrations of NP-SLN were measured by reverse-phase high pressure liquid chromatographic (RP-HPLC) method with nitrendipine as internal standard. Coefficients of variation of within-day and between-day were 1.13-6.73% and 1.41-9.09%, respectively. Absolute recoveries rate of nifedipine and internal standard were 90.37-94.88% and 88.23-95.63%, and analytical recovery rate of nifedipine was 95.09-102.21%. All pharmacokinetic data were treated by 3P97 software, then parameters were calculated and curve-equations were fitted..Results: The mean particle size of NP-SLN produced by HPH method was about 158nm; the polydispersity index (PI) was 0.689, and the span was 0.899. These data suggested that the NP-SLN has a better narrow distribution. Drug incorporation rate and loading capacity of NP-SLN were 45.22% and 30.14%, respectively.Re-dispersing the transdermal agents contained NP-SLN can get a SLN with similar particle size, but particle distribution turn broad slightly. The results of pharmacokinetic experiment in rabbits suggest that NP-SLN, which given by both intravenous and transdermal route to take on a typical slow and delayed release. After calculated by 3p97 package, the pharmacokinetic process of NP-SLN in rabbit accords with open two-compartment model. The curve equation of intravenous and trandermal route are , respectively; Main pharmacokinetic parameters were: T]/2(a): 0.29?.09 and 2.36?.42h; T,/2(P): 7.8U1.30 and 14.30?.54h; MRT: 7.03?.24 and 10.43+0.21h;K10:0.24+0.04and0.15+0.01h-1; AUC0-t: 1.35+0.28and 1.25+0.18ug/ml-h; Vd: 0.58?.08 and 5.40?.89L, respectively. Pharmacokinetic parameters within two routes were statistically different (P<0.05). NP-SLN given by transdermal route, in contrast with traditional nifedipne transdermal patch, characterized by fast absorption, earlier peak concentration, and subsequently delayed release.Conclusion: Through high pressure homogenization method, we can produce nifedipine-loaded cetylpalmitate solid lipid nanoparticles with smaller particle size and higher load capacity, which stabilized by complex emulsifier. The study of pharmacokinetics of NP-SLN shows that the agent has the characterization of both slow and delayed release. When it was applied in percutaneous drug delivery, the agent can enhance the transdermal rate efficiently, reduce absorption time, and prolong duration of action. Therefore, NP-SLN is a promising new agents.