| Transdermal drug delivery system (TDDS) , that delivers drug through skin, in many cases shows advantages over oral and injection delivery methods. TDDS is more effective by avoiding gastrointestinal metabolism and associated side effects. However, it is handicapped by the low skin permeability caused by the stratum corneum (SC) of the outer skin layer, The bilayers have a highly ordered structure that makes the SC impermeable to many drugs. To overcome the main limitation of transdermal delivery (low permeability), innovative technologies have been developed in an attempt to increase transdermal drug delivery. Ultrasound drug delivery system(sonophoresis or phonophoresis) is one of effective physical methods to increase drug delivery through SC.but there is few report on native agents.Both sinomenine hydrochloride (SH) and lappaconitine hydrobromide (LH) are effective composition monomer extracted from traditional Chinese medicine. They are widely used in clinical for analgesic and anti-inflammatory effect , several studies on their transdermal delivery have been reported,mainly focusing on chemical enhancers and preparation formulation screening. Is sonophorsis an effective method for improving two drugs transdermal delivery? On the other hand, these two drugs are containing base, having higher polar and the same melting point. However, molecular weight of lappaconitine hydrobromide is almost twice compared to that of sinomenine hydrochloride. Hence, to study the effect of sonophoresis on two drugs have clinical as well as experimental significance.Two ultrasound frequencies (800KHz,1MHz) were applied with a sonicator with a transducer in the present study. Male SD rates skin as model and carbomer934 gel was used as ultrasound couplant.From the research results, the transdermal parameters per unit cumulative absorbing quantity (Q8hr) and steady sate penetration rate(Js) of SH were increased 2.15, 2.15 times and 10, 6.5 times, respectively. In the case that the ultrasound frequency(F) was 800KHz,exposure time(T) was 10min, and applied intensity(I)was 0.75W/cm2 compared to that of passive diffusion.. On the othe hand,when the sonophoresis parameters were F=lMHz,T=10min,I=0.7 W/cm2 , Q8hr and Js of SM was 8.9 times identically. But for LH, the value was increased 20 and 22 times, respectively. Thus it can be concluded that sonophoresis was effective to increase the transdermal absorbtion of these two drugs..Sonophoresis parameters also affected its effective in some degree. In the condition (F=800KHz, T=10min,I=1.5W/cm2),the Q8hr,Js value of SH increased almost twice compared to that with I=0.75W/cm2. If fix the applied intensity, changed the exposure time, the Q8hr,Js value of SH increased almost 3 times when exposure time was 10min compared with that was 5min. But for LH,it did not changed remarkably, and at the condition of I=3 W/cm2,T=2.5min, Q8hr Js of LH increased 2.7, 3.2 times to I=0.75W/cm2, respectively.. If exposure time changed to 10min,the parameters of LH Q8hr=31.38±6.12μg/cm2, Js=5.82±0.41μg·cm-2·h-1,and when T=2.5min, Q8hr=24.16±4.44μg/cm2, Js=2.85±0.36μg·cm-2·h-1, But when Applied intensity keeping 0.75w/cm2,two groups had remarkable difference. The same result was founded when F=lMHz, I=0.7W/cm2, T=5min or 10min. According to these data,the effect of parameters of sonophoresis on transdermal delivery was related to the characteristis of drug. And to SH, the parameters of sonophoresis was directly related to the transdermal absorbtion.Some chemical permeative enhancer such as alcohol, 1,2- propanediol, Azone and oleic acid,can improve the transdermal permeation of SH and LH. Better effective action was found from sonophoresis than passive diffusion at the condition of F=800KHz, I=0.75w/cm2, T=10min,and couplant containing 10% 1,2-propanediol(P<0.05). The SH transdermal parameters of sonophoresis was Js=22.59±3.44μg·cm-2, Q8hr=184.63±48.10μg·cm-2·h-1, and the parameters of passive diffusion was Js=4.40±0.42μg·cm-2,Q8hr=34.16±6.66μg·cm-2·h-1. They were increased 5.13 times and 5.38 times, respectively. It was noticeable that the transdermal absorbtion rate increased 24 times and 50 times when skin was pretreated with Azone and oleic acid for 12 hr, and increased 9 times,2.8 times, respectively, after sonophoresis with F=800KHz,I=0.75/cm2,T=10min, which is possible for clinical using. Q8hr and Js of LH also increased compared withthat of passive diffusion (P<0.01), with LH gel containing 10%l,2- propanediol. The Q8hr and Js of LH was 2.73 and 2.69 times with sonophoresis when the gel containing 10% 1,2- propanediol+3%Azone. The results demonstrated that chemical enhancer combined with sonophoresis will be useful method to increase the transdermal absorbtion of drugs.The histopathological findings revealed that there was almost no change observed in the structure of skin after sonophoresis. However, the scanning electron microscope revealed that surface of SC had been changed with sonophoresis, and the phenomenon probably due to cavitation induced by the ultrasound.In conclusion, sonophoresis was demonstrated that it is a useful and effective method for two composition monomers extracted from traditional Chinese medicine to enhance their transdermal absorbtion,and this open the way for clinical study.
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