Research The Effect Of Dihydropyridine Drugs On The Microstructure Of Lipid Fat Emulsion Based By NMR

Lipid fat emulsion is O/W emulsion which is made by oil phase,water phase,emulsifier and other regulators.It is a good carrier of poorly water-soluble drugs,which can significantly improve the entrapment efficiency and stability of drugs.In addition,the lipid fat emulsion as drug delivery carrier with many advantages and wide market prospects to achieve the target or reduce the side effect.But the lipid fat emulsion is a thermodynamic unstable system,and its stability is still the key problem in the present study,which the formulation and the preparation process may affect the stability of the emulsion.Due to the lipophilicity and surface activity of some drugs,the loading of drugs often change the emulsified membrane of the lipid fat emulsion and affects its stability.It is considered that the microscopic structure of the lipid fat emulsion was of great importance to the stability of emulsion.This project intends to use~1H-NMR technology research the effects of loading dihydropyridine drugs nimodipine and felodipine on the microscopic structure of lipid fat emulsion,meanwhile,the stability of the emulsion will be evaluated comprehensively through combining the average particle size and the centrifugal stability constant.Firstly,the low temperature ultracentrifugation and ultrafiltration centrifugation were adopted to study the phase distribution of drugs in nimodipine lipid fat emulsion.Results demonstrated that about 0.47%of the free drug in the water phase,about 14.91%drugs exist in the micelle or liposome structure,about 34.03%of the drug in oil phase,about50.59%of the drug in the oil-water interface layer.This preliminary reminded us that the poorly water-soluble drugs mainly solubilized in the oil-water interface layer of submicroemulsion,which may change the properties of the lipid fat emulsion.To determined there is a interaction between the components,we studied the changes of ~1H-NMR spectra of the drug and various components in the lipid fat emulsion.The change of the characteristic peak intensity in the ~1H-NMR spectrum of the lipid fat emulsion was analyzed to speculated that the effect of loading the drug on the arrangement of emulsifiers at the oil-water interface,thus affecting the formation of the emulsified membrane and the microstructure of emulsion.The effect of different concentration of nimodipine on the microstructure of emulsion was studied by ~1H-NMR,which observing the changes of molecular interaction at the oil-water interface.It is resulted that the change trend of the intensity of characteristic peak in the ~1H-NMR spectrum of lecithin first decreased,then increased and decreased again with the increase concentration of nimodipine lipid fat emulsion.It is presumed that nimodipine distributed at the oil-water interface acts with lecithin molecules with the increase of the dosage,which makes the arrangement of lecithin change,thus affecting the microstructure of lipid fat emulsion.When the drug concentration was 0-0.15 mg/mL,the intensity of characteristic peak decreased.It is suggested that nimodipine dispersed into the monolayer formed by lecithin and enhanced with the interaction of lecithin molecules,so the lecithin molecules became tightly arranged on the oil-water interface and had stabilizing effect on the emulsified membrane.But when the nimodipine lipid fat emulsion concentration was 0.2 mg/mL,the intensity of characteristic peak began to increase.It is speculated that with the increasing dosage of nimodipine,a part of it will form single emulsion membrane,the remaining small amount of lecithin molecules will arrange outside of the scattered single emulsion membrane and became relatively unstable.With the increase of nimodipine dosage was enough to form the bilayer membrane,the emulsion film became stable again.Due to the intensity and tightness of the emulsion increase,the intensity of characteristic peak decreases,which is the most stable when the concentration is close to 0.75 mg/mL.At the same time,the stability of the emulsion was evaluated comprehensively through combining the average particle size and the centrifugal stability constant,the results were consistent with the nuclear magnetic conjecture.Finally,in order to study and analysis more thoroughly the effect of dihydropyridine drugs on the stability of lipid fat emulsion,we will conduct a study on the felodipine,which it is a strong lipophilic drugs.It is resulted that with the increase concentration of felodipine lipid fat emulsion,the change trend of the intensity of characteristic peak in the~1H-NMR spectrum of lecithin first decreased,then increased and decreased again.The results showed that the peak intensity was the lowest when the concentration of felodipine lipid fat emulsion was 0.3 mg/mL and 0.9 mg/mL,and the stability of the emulsion was better.At the same time,the results of average particle size and centrifugal stability constant were consistent with the nuclear magnetic conjecture.Furthermore,this result was in accordance with nimodipine,the drug of the same model.Summarized,loading the dihydropyridine drugs nimodipine or felodipine can cause the change of the lecithin molecular arrangement and the microstructure as well as influence the stability of the lipid fat emulsion.But the drug concentration of felodipine is required to reach influencing the stability of emulsion was greater than nimodipine,it mainly depends on the differences in the structure and physicochemical properties of the drugs.This subjec had an important significance for increasing efficiency and minimizing cost during the development of stable emulsions.