The Preparation Of Drug Nanoemulsion By High-gravity Technology

Nowadays,most commercially available drugs have poor bioavailability due to drug problems such as low solubility,low permeability,and first-pass effects.Therefore,drug delivery systems have become one of the focal issues of pharmaceutics.Nanoemulsion has a wide range of advantages as a new drug delivery delivery.In this paper,the nanoemulsion was prepared by using high-gravity technology.The effects of surfactant types,co-surfactant types and dosage,temperature,rotation speed and emulsification time on the particle size were studied.The in vitro dissolution and cell permeability of the drug nanoemulsion were tested.The stability of the nanoemulsion was investigated.The main conclusions are as follows:The composition and dosage of nanoemulsion were determined by pseudo-ternary phase diagram,and glyceryl triacetate was used as oil phase,RH-40 as surfactant,1,2-propanediol as co-surfactant with ultrapure water.It is a self-emulsifying system,which the ratio of O:Sf:Cosf:W is 8.75:2.5:1.25:87.5(w/w/w/w).The discussion of the process conditions found that the effect of the process is far less than the impact of the system composition itself.Therefore,the final experimental conditions were set at a temperature of 25?,a rotational speed of 500 r/min,and a mixing time of 10 min.At this time,the nanoemulsion droplet size is about 15 nm,the droplet dispersion is uniform,the appearance is clear and transparent,and the solution performance is good.When a high-gravity rotating packed bed is used as the emulsification reactor,the amount of surfactant is greatly reduced.Compared with the self-emulsifying formula,the Smix dosage is reduced by 75%.At this time,the nanoemulsion droplet size is still maintained at about 15 nm,and the particle size distribution is narrow.The 30-day stability test found that the sample prepared by RPB had good stability,the particle size remained at 15 nm,and the appearance was clear and transparent,while the sample droplet size prepared by the self-emulsification method was larger than 500 nm,and the appearance was turbid.The cell permeability,dissolution performance and liver protection performance of BCSII drug Silybin nanoemulsion were tested.The ccell permeability of Silybin nanoemulsion is twice that of commercially available capsules,while the amount of excretion is only 0.5 times that of commercially available capsules.In the in vitro drug release test within 24 hours,the Silybin nanoemulsion had a cumulative drug release of 95%,while under the same conditions the nanocomposite powder was 81%and the silybin capsules were only 34%.In liver protection performance,when the nanoemulsion drug content is 100 ?g/mL,the cell survival rate is higher than 95%.The cell permeability of the BCS class ? drug Rosuvastatin Calcium was tested.The experiments found that in the A-B direction,the amount of permeation was significantly increased by Rosuvastatin Calcium nanoemulsion,which was 3.5 times that of commercially available tablets;in the B-A direction,the amount of excretion was reduced,which was 0.76 times that of commercially available tablets.The nanoemulsion can be stabilized for a long time by dilution with pure water,0.1 mol/L HCl,FassIF and FassGF.The results of two-week accelerated experiments show that the nanoemulsion remains stable under strong-light,high-temperature and high-humidity conditions.After one year of storage at 4? and 25?,the droplet size remained at 15 nm,but the drug content decreased slightly.