Comparison Of Three Novel Ibuprofen Transdermal Vesicles And Preparation And Evaluation Of Binary Ethosomes Thermosensitive Gel

AIM(1) Ibuprofen was chosen as the model drug to prepare ethosomes, binary ethosomes and solid lipid nanoparticles, then compare the skin permeation of three novel transdermal vesicle.(2) The excellent ability of penetration through skin from three lipid vesicles were used to prepare thermosensitive in situ gel, and investigated the feasibility of novel ibuprofen transdermal vesicle thermosensitive gel as transdermal drug delivery preparation.METHODS(1) Insusing method was used to prepare ibuprofen ethosomes and binary ethosomes, ibuprofen solid lipid nanoparticles was prepared by emulsion with a high temperature-low temperature curing method. These lipid vesicles were prepared and characterized by shape, size, zeta-potential and entrapment efficiency. The excellent ability of penetration through skin from three lipid vesicles were used to prepare ibuprofen lipid vesicle gel with a cold digestion method, and determined the gelation temperature by stirring method.(2) The single factor experiment was used to optimize formula of ibuprofen ethosomes, binary ethosomes, solid lipid nanoparticles and lipid vesicle gel.(3) Franz diffusion cells were used for the percutaneous absorption studies of ibuprofen ethosomes, binary ethosomes, solid lipid nanoparticles.(4) The dialysis method was used to study release of ibuprofen lipid vesicle gel in vitro.(5) HE staining was used to show skin irritation of mouse skin influenced with ibuprofen lipid vesicle gel.(6) The stability of ibuprofen ethosomes, binary ethosomes and solid lipid nanoparticles was determined by storing these vesicles at4℃or room temperature, the EE of vesicles were measured at various times (0,1,2and3months). The stability of ibuprofen lipid vesicle gel was determined by storing the lipid vesicle gel at constant temperature of40℃or refrigerator at-20℃and avoid light preservation, the appearance characters, content of drug and gelation temperature of lipid vesicle gel were observed and measured at various times (5and10days).RESULTS(1) Ibuprofen ethosomes, binary ethosomes (Ethanol-PG=7:3, v/v) and solid lipid nanoparticles were spheroid or spheroid-like vesicular structure. The average size of these vesicles were (108±4.3) nm,(103±5.6) nm and (195.2±16.88) nm, respectively. The Zeta potential of these vesicles were (-9.8±4) mv,(-8.25±3.2) mv and (-22.3±6.94) mv, the EE of optimize formula of ibuprofen vesicles were (72.93±1.12)%,(73.58±1.35)%and (73.61±1.42)%, respectively.(2) Different proportion of ethanol and propylene glycol lead to different transdermal characteristic, the drug showed the best permeation ability when their proportion was7:3.(3) The cumulation penetration quantity of drug from ibuprofen ethosomes and binary ethosomes (Ethanol-PG=7:3, v/v) was8.95and16.35times higher than solid lipid nanoparticles, respectively. The retention amount of solid lipid nanoparticles was greater than ethosomes and binary ethosomes in skin after24h, there were significant differences(P<0.01).(4) The gelation temperature was (32±1.1)℃, which was get by using32.2%poloxamer407and3.22%poloxamer188as bases to prepare ibuprofen binary ethosomes thermosensitive gel. Ibuprofen binary ethosomes thermosensitive gel demonstrated more significant effect than binary ethosomes in delaying the release of ibuprofen.(5) Histopathology of skin test showed that ibuprofen binary ethosomes thermosensitive gel did not cause significant changes in the structure of skin tissue.(6) The EE of ibuprofen ethosomes, binary ethosomes and solid lipid nanoparticles showed no significant changes with in3months at4℃or room temperature. The appearance characters, content of drug and gelation temperature of binary ethosomes thermosensitive gel showed no significant changes with in10days at40℃or-20℃.CONCLUSION(1) Ibuprofen ethosomes, binary ethosomes (Ethanol-PG=7:3. v/v) and solid lipid nanoparticles were spheroid or spheroid-like vesicular structure. EE of ibuprofen three lipid vesicles was no significant difference.(2) Ethosomes, binary ethosomes and solid lipid nanoparticles all could improve the transdermal delivery of ibuprofen, the penetration ability through skin of binary ethosomes (Ethanol-PG=7:3, v/v) was the strongest; the accumulate ability in the skin of solid lipid nanoparticles was the strongest.(3) Ibuprofen ethosomes, binary ethosomes, solid lipid nanoparticles and binary ethosomes thermosensitive gel prepared were all stable.(4) The results of in vitro release showed that ibuprofen binary ethosomes thermosensitive gel had obvious advantages compared with binary ethosomes in delaying the release of ibuprofen. The results of irritation indicated that ibuprofen binary ethosomes thermosensitive gel had no obvious skin irritation.