Preparation,characterization And Antifebrile Activity Evaluation Of Ibuprofen Nanoparticles For Transdermal Delivery

Ibuprofen(IBU)is a kind of Non-steroidal anti-inflammatory drugs,has different effects such as anti-inflammatory,analgesic and antipyretic.It has a significant role in the treatment of mild to moderate hemicrania episodes and preventive treatment,arthropathy and myopathy,body pain and pain after surgery and trauma.However,the application of ibuprofen is restricted to its low aqueous solubility and gastrointestinal side effects.This article applies the high-pressure emulsion solvent evaporation method to prepare ibuprofen nanoparticles.The optimal conditions selected by single-factor method,the main contents are as follows:the surfactant types,the surfactant concentration,the volume ratio of water phase and organic phase,the concentration of ibuprofen,the homogenate speed,the homogenate time,the homogeneity times,the homogeneity pressure and the cryoprotectant types.The optimum conditions were:the concentration of emulsifier OP-10 was 5 mg/ml,the volume ratio of water phase and the organic phase was 30,the concentration of ibuprofen was 200 mg/ml,the homogenate speed was 6000 r/min,the homogenate time was 5 min,the homogeneity cycles was 7 times,the homogeneity pressure was 350 bar,the cryoprotectant was mannitol and its concentration was 600 mg.Under the optimum conditions,ibuprofen nanosuspension with an MPS of 51.5 nm were obtained,ibuprofen nanoparticles with an MPS of 216.9 nm were obtained after lyophilization.The properties of raw ibuprofen and ibuprofen nanoparticles were characterized by scanning electron microscopy(SEM),fourier transform infrared rpectroscopy(FTIR),high performance liquid chromatography(HPLC),liquid chromatography-mass spectrometry(LC-MS),X-ray diffraction(XRD),differential scanning calorimetry(DSC),thermal gravimetric analysis(TG),saturation solubility and dissolution rate.The analysis measure resulted that the ibuprofen nanoparticles had be converted into an amorphous state after preparation,but its chemical structure had not changed.The solubility and the dissolution rate of ibuprofen nanoparticles were about 80.3 times and 1.82 times of raw ibuprofen.The GC result showed that the residual ethanol and chloroform of ibuprofen nanoparticles was 170 ppm and 9.6 ppm respectively less than the ICH limit(5000 ppm and 60 ppm)and it was suitable for pharmaceutical use.The transdermal ability of raw ibuprofen and ibuprofen nanoparticles were investigate by the in vivo and in vitro transdermal penetration test.In the in vitro transdermal penetration test,the cumulative permeation amounts of ibuprofen nanoparticles was higher than raw ibuprofen and physical mixture from 10 minutes,and 74.73?g/(h·cm2),35.97 gg/(h·cm2),31.91?g/(h·cm2)of the drugs were permeated from ibuprofen nanoparticles each hour,raw ibuprofen and physical mixture.In the in vivo transdermal penetration test,the plasma concentration of ibuprofen nanoparticles transdermal group reached a high level at 10 min,Tmax was 1.5 h,Cmax was 16.416 ?g/ml,AUC was 33.597 mg/L*h;the Tmax of the raw ibuprofen oral group was 1 h,Cmax was 6.707 ?g/ml,AUC was 15.747 mg/L*h;the Tmax of the raw ibuprofen transdermal group was 1 h,Cmax was 3.396 ?g/ml,AUC was 14.626 mg/L*h.The AUC of the ibuprofen nanoparticles group was about 2.30 times and 2.13 times of raw ibuprofen oral group and transdermal group.In the antifebrile experiment,the ibuprofen nanoparticles had a good antipyretic effect of fever rats on three doses.The temperature of nano-transdermal group with low-dose lowered 1.05? at 0.5 h after treatment,meanwhile,the temperature of gavage group lowered 0.67?.The temperature of nano-transdermal group with mid-dose lowered 0.92? at 0.5 h after treatment,and the temperature of gavage group lowered 1.07?.The temperature of nano-transdermal group with high-dose lowered 0.74? at 0.5 h after treatment,the temperature of gavage group lowered 1.11?.The nano-transdermal gel has a high and stable cooling rate and a long cooling duration in low dosage.All the results above showed that we prepared the ibuprofen nanoparticles with a uniform particle size by the high-pressure emulsion solvent evaporation method.The analysis measure resulted that the ibuprofen nanoparticles had been converted into an amorphous state after preparation,but its chemical structure had not changed,the solubility and the dissolution rate were improved.At the same time,the ibuprofen nanoparticles had a good transdermal effect in the in vivo and in vitro transdermal penetration test.In consequence,the ibuprofen nanoparticles had a good prospect in the future.