Studies On The Preparation Of Lidocaine Hydrochloride Poultice And Its Pharmacokinetics

Lidocaine Hydrochloride is frequently used in clinics as one of local anesthetics. Recently it is used for the treatment of PHN. The main kind of dosage forms marketed is injectable preparation so that patients are short of complaisance, and the local necrosis will emerge in the injection site. In order to be administrated conveniently, the poultice of lidocaine hydrochloride was formulated and studied to make up for vacancy of this area in our country. According to the rule of drug register, formula screening, pharmacokinetics, security and quality standard had been studied.The main adjuvant is new-fashioned water-soluble polymer—viscomate NP 700. Screen the formula of the base material of poultice by orthogonal design. Using Franz-type diffusion cell and mouse skin in vitro as transdermal barrier, the concentration of lidocaine hydrochloride in different kinds and concentration enhancers was determined by UV, then cumulative permeation quantity (Q)and the penetration rate(k) of lidocaine hydrochloride poultice was calculated. The ordering of the effects of penetration enhancers is propylene glycol>azone>menthe-camphor>carbamide. But only propylene glycol and azone have significance(P<0.05), menthe-camphor and carbamide have no effects.It suggested that 5% propylene glycol and 1% azone could be the penetration enhancer for lidocaine hydrochloride poultice.The HPLC was used to assay the plasma concentration of lidocaine hydrochloride. The comparison drug was lidocaine patch (Lidoderm) which was produced and sold in Japan. The two patches were given to rabbits in single dose manner. The metabolic process of the self-made patch fitted to two-compartment model with first order absorption, while the metabolic process of the comparison patch fitted to one-compartment model with first order absorption. The main pharmacokinetic parameters of Lidoderm and our patch were: Ka:(3.1369±1.8404h^-1) &(3.3784±4.2840h^-1); Lag- time: (0.0549±0.0544h)&(0.0614±0.0754h);t1/2(ka):(0.2974±0.1606h)&(0.5947±0.5443h);T_(peak): (1.2257±0.5560h)&(2.5440±1.3028h);C_max:(0.2952±0.1241μg·mL^-1)&(0.2848±0.1790μg·mL^-1);AUC:(9.9240±5.5268μg·h·mL^-1)&(11.7565±6.5723μg·h·mL^-1);CL/F(s):(5.8951±1.9426mg·h^-1·μg·mL^-1)&(5.5912±4.0117mg·h^-1·μg·mL^-1);V/F(c):(178.6736±112.7002mg·μg^-1·mL)&(247.8692±196.5962 mg·μg^-1·mL). The results showed no significant difference for AUC,Cmax, Ka, Lag time, V/F(c), T_1/2(Ka), CL(s) between the tow preparations(P>0.05), showed significant difference for T_peak(P<0.05). It is concluded that the self-made patch effected more quickly than the comparison. The relative bioavailability of the self-made lidocaine hydrochloride poultice was 84.41%.According to the requirements of preparation in ChP, characteristics, identification, examination and assaying had been studied.It was proved that lidocaine hydrochloride poultice has no skin irritation or irritability.