| Plumbagin is the main active ingredient extracted from the root of Plumbago zeylanica L.,and its alcohol solution is used for the treatment of body fluid extravasation,body tinea,bruises in clinical practice.Modern pharmacological studies have shown that plumbagin has a wide range of activities,such as anti-inflammatory analgesic,antibacterial,anti-tumor,anti-liver fibrosis.However,due to poor solubility,low melting point,easy sublimation and toxicity of plumbagin,its utilization is limited.The purpose of this paper is to make plumbagin into transdermal delivery preparations for the treatment of arthritis disease.The plumbagin transfersomal gel can not only increase the drug solubility,but also reduce the toxic and side effects of the drug and enhance the compliance of the patient.1.Preformulation study.The analytical methods of plumbagin were established by UV spectro-photometer and UPLC.The methodological study indicated that the established analytical methods were accurate and feasible.The solubility of plumbagin in different media was investigated.The acceptor solution of the transdermal diffusion test of plumbagin was determined to be 30%ethanol PBS?pH7.4?.The effects of low temperature high-speed centrifugation and Sephadex G50 column chromatography on the encapsulation efficiency of plumbagin were measured.Sephadex G50 column chromatography was selected to determinate entrapment efficiency.2.Preparation of plumbagin transfersomes and evaluation of its pharmacokinetic properties.Plumbagin transfersomes were prepared by flim-ultrasound methond,using central composite design and response surface method to select the best prescription condition with the entrapment efficiency?EE%?,Zeta potential,and the average particle size as the evaluation indexes.The optimal prescription condition was determined as drug 10.0 mg,phospholipoids 700.0 mg,Tween-80 91.5 mg,ultrasonication time 13 min.According to the optimal prescription,EE%,the average particle size,the polydispersity index,and Zeta potential of plumbagin transfersomes were?79.88±2.26?%,?125.64±4.54?nm,?-30.97±1.13?mV,and its distribution was even.The stability test results showed that the plumbagin transfersomes were uniform and stable within 60 days at 4?,and significant drug leakage didn't occur.3.Transdermal study of plumbagin transfersomes in vitro.The vertical Franz diffusion cells were used to investigate the transdermal permeation effect of plumbagin transfersomes with the cumulative permeation amount and retention of the skin per unit area as an index.The results showed that the cumulative permeation rate?67.01%?and retention(0.81?g·cm-2)of plumbagin transfersomes in vitro were higher than that of plumbagin solution(cumulative permeation rate was 58.82%,skin retention was 0.33?g·cm-2),indicating that plumbagin transfersomes can increase the solubility,stability,and improve permeability of the drug.4.Preparation and transdermal study of plumbagin transfersomal gel in vitro.Based on the above research work,plumbagin transfersomes were prepared as gel.Taking the cumulative permeation amount of plumbagin as an index,prescription of gel was optimized through orthogonal test.Optimal prescription was 1%carbomer940 as gel matrix,and 5%glycerol as the humectant.The results of transdermal test showed that the cumulative penetration rate?70.04%?and retention amount of skin(0.52?g·cm-2)of plumbagin transfersomal gel were better than that of plumbagin gel(the cumulative penetration rate was 65.60%,retention amount was 0.36?g·cm-2,P<0.01).5.Skin irritation evaluation.Plumbagin transfersomal gel was applied to the depilated skin of guinea pigs to investigate its irritation to the skin.The results showed that the short-term use of plumbagin transfersomal gel had no skin irritation.The use of transfersomal gel significantly increased the stability of plumbagin,improved its skin penetration rate and retention amount.This article provides pre-experimental studies for the exploitation and utilization of plumbagin preparations as transdermal drug delivery. |
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