Studies On Transdermal Delivery System Of Lidocaine Electret Gel Patch

Electret is the functional dielectric material which can keep the space charge and dipole for long time. After the electret being applied to skin, the external electric filed produced by electret can alter the arrangement of lipid molecules in the outmost layer of skin-the stratum corneum, forming many transient permeable apertures and enhancing the transdermal drug delivery. In order to make more systemic study of the enhancing effect of electret on transdermal delivery of ionic drugs, to explain the transdermal enhancement mechanism of electret and to prepare a new transdermal drug delivery formulation, we selected porous polytetrofluorethylene (PTFE), polyethylene (PE) and polypropylene (PP) as the study objects for the excellent charge storage stability of PTFE, low melting point of PE and humidity resistance of PP. By means of corona charging, all the porous PTFE samples were made into electrets at 175℃ with corona voltage of ±800V and grid voltages of 200, 400, 600, 800, and ±1000V. Then the porous PTFE, PE and PP were melted at 105°C for 30min to prepared the porous PTFE/PE/PP composite electret which will be used later for the study of charge storage stability when it being applied to lidocaine aqueous, the study of its transdermal enhancing effect on ionic drug, the comparative study of drug transdermal enhancing effect with commonly used permeation enhancers, and the preparation study of lidocaine electret gel patch system.Lidocaine, a moderate local anesthetic with the molecular formula of C₁₄H₂₂ON₂·HCl·H₂O, is frequently used as a model drug in study of transdermal drug delivery system, and as well as was used in this paper. The in vitro permeation experiment was carried out in improved Franz diffusion cell to make the comparative study of the enhancing effect of some commonly used chemical permeation enhancers with electret on lidocaine transdermal delivery. The chemial permeation enhancerused here were azone, lactic acid and propylene glycol. The accumulative penetrated amount was calculated by determining the concentration of lidocaine in receptor cell by means of high performance liquid chromatograph (HPLC) equipped with a Waters Millennium³² workstation. An Irregular-H C18 column (4.6mmx250mm, 5μm) and 510 constant current pump were used. The mobile phase was 240 : 160 : 0.29 : 0.14 of methanol-water-triethylamine-acetic acid combination at the flow rate of 1.0 ml/min. The UV detective wavelength was set at 220nm and the detection sensitivity was 0.01AUFS.The results indicated that 1) Positive porous PTFE/PE/PP electret had significant enhancing effect on lidocaine transdermal delivery. The accumulative penetrated amount of lidocaine in electret group (Q_electret) was 1.5 to 8.2 times that of in control group (Q_control) after the electret being applied for 0.5²4hr. 2) The higher the surface potential of postive porous PTFE/PE/PP electret, the larger the Qeiectret was. 3) Different transdermal enhancing behaviors were exhibited when the positive porous PTFE/PE/PP electret had different surface potential. With the increasing of time, the ratio of Qeiectret to Qcontroi raised exponentially in case of the electret' surface potential being lower than 800V, but the ratio decreased expotentially with time if the surface potential of electret was larger than or equal to 800V. 4) The lidocaine transdermal enhancing effect which resulted from the application of different chemical permeation enhancers or electret were ranged in the following order: 3% Azone > 5% Azone > positive electret > 10% lactic aicd ≈ 1% Azone > negative electret > 1% menthol > 20% propylene glycol. Positive porous PTFE/PE/PP electret should be a better means to enhance the drug transdermal delivery. 5) In the combination usage of Azone with electret, +1000V porous PTFE/PE/PP electret markedly increased the transdermal enhancing effect of 1% Azone and 5% Azone on lidocaine, except for a little bit decrease that of 3% Azone. There was a cooperation effect in lidocaine transdermal enhancement between +1000V porous PTFE/PE/PP electret and 1% Azone or +1000V porous PTFE/PE/PP electret and 5% Azone.Furthermore, matrixes of carbomer U10, carborite 7S etc. were used in this article to prepare the lidocaine electret gel patch. By means of uniform design study and...