Study On The Preparation Of Lappaconitine Cataplasm And Its Quality Standard

Objective: Lappaconitine is a first patent non-dependence analgesia drug in domestic.It has strong analgesic effect,the effect of postoperative pain is particularly significant.It usually take oral and intravenous injection,intramuscular injection for pain treatment in the clinical.But oral drug bioavailability is low,and gastrointestinal irritation and the liver first pass effect is existed.Although the injection have high bioavailability,but its half-life is short,dosing frequency.Take it into the percutaneous preparations will avoid the liver first pass effect,extend the action times,and reduce the toxicity and side effects.Our group was carried out the preparation of Lappaconitine cataplasm and researched the relevant quality.(The patent of Lappaconitine cataplasm researched by our group with Zhejiang university of Chinese medicine have already submitted an application for a patent for invention.Now at the open stage.)Methods:The preliminary research of the project group has determined the solubilizerand the basic formula ofcataplasm,using the parameter of rheology to screen filling agent;to establish a analysis method forexactand dependable in vitro of HPLC.Using skin of SD rats to in vitro percutaneous penetration test,Screening of transdermal promoter and research key prescription and process.For example,the filling agent,theamount of drug,and the thickness to the Lappaconitine cataplasm.Compared with the listed Lappaconitine adhesive patch to determine the optimal formula and process.This paper preliminary studies on the quality study of Lappaconitine cataplasmandcarried out a preliminary study of stability.Results: Rheological data show that the effects of the filling agent forviscous modulus and elastic modulus is: Colloidal Silicon Dioxide> PVPP > kaolinite > maltodextrin.Colloidal Silicon Dioxide effect is remarkable,so choose as a the filling agent ofcataplasm.In vitro transdermal tests showed that the transdermal accords oflappaconitine cataplasm with zero order kinetics equation,lappaconitine in the test samples and comparison products in the 72 hours of cumulative osmotic quantity were 204.02 mg and 210 mg,transdermal rate is 2.75 and 2.72.It showed no significant difference in the above data of the test samples andcomparison products by t-examination(P>0.05).The optimal formula of lappaconitine cataplasm is NP-800 was6%,Dihydroxy aluminium aminoacetate was 0.25%,Colloidal Silicon Dioxide was 2%,glycerol was 20.2%,tartaric acid was 0.25%,distilled water was 42%,PVA was 2%,Lappaconitine was 20%,pharmasolve was 20%,Laurocapram was 2%,Arabic gum was 2.5%,twain–80 was 0.8%.After mixed coating by Coating machine for 1 mm thickness.Lappaconitine cataplasm is the almost white flakecataplasm.all the examination indexes in accordance with Chinese pharmacopoeia standards,the average paste content is 11.84/100 cm2,the adhesion is good.Determination the Contentof Lappaconitine cataplasm by HPLC.Linear regression with peak area and concentration,The standard curve is A=13.195C+2.4004,The linear range of calibration curveis0.5～50.0 μg·m L-1.(r=0.9999).Sample recovery rate of low,medium and high concentrations are 98.77%,100.23%,98.53%,the precision is 0.47%,The stability of 24 h is 1.02%.The average content of three batches of lappaconitine cataplasm are 100.47%,100.43%,99.97%.24 hours in vitro release degree up to 70.06%.About the amount of total impurities in the material inspection at around 1.1%.influence factor test shows that,light,heat,humidity and other factors have different degree of influence on Lappaconitine cataplasm stability.Conclusion:The transdermal rate of Lappaconitinecataplasm is closed to the listed lappaconitine adhesive patch,its quality conform to the requirement of Chinese pharmacopoeia.