Study On The Preparation Of A Novel Oral Topical Anesthetic And The Permeation In Vitro

Background:In oral clinic, topical anesthesia can be used to release fear and side effects caused by injection. But how to increase anesthetic infiltration and onset becomes the core problem.Objective:To establish a high performance liquid chromatographic (HPLC) method of determination of lidocaine hydrochloride (LID). To prepare a novel topical anesthesia polymeric liposomes and study its characters of permeation through mouse skin in vitro.Methods:A HPLC method of.determination of lidocaine hydrochloride was established and certificated. The specificity, precision, recovery, stability were examined. The novel topical anesthesia preparation was prepared with LID loaded polymeric liposomes (LID-PLs) based on octadecyl quaternized lysine modified chitosan (OQLCS)/Cholesterol. LID-PLs and LID-loaded conventional liposomes (LID-CLs) were prepared by reverse-phase evaporation method. Morphology was observed with a transmission electron microscope. The diameters and zeta potential of LID-PLs and LID-CLs were determined by dynamic light scattering (DLS) using a Brookhaven Zetasizer. Entrapment efficiency was determined by glucose gel column chromatography. The isolated mouse skin and Franz diffusion cell were used to evaluate the characters of permeation of LID-PLs,LID-CLs and lidocaine hydrochloride injection (LID-IJ).Results:The specificity and sensitivity of HPLC were high. The retention time of LID was3.899min andblank polymer liposomes, blank transdermal receiving fluid had no interference on the absorption peak of LID. The standard curve equation was Y=0.0516X-2.3978, r=0.9998. The intra-day and inter-day precision were all less than1.35%and the recovery rate was between99.5%and102.2%. The diameters of LID-PLs were significant smaller than those of LID-CLs (61.2±8.14nm vs219±7.51nm). Encapsulation efficiency was (70.5±3.21)%.5min,10min,30min,2h,4h,6h,8h,12h and24h after administration, the main cumulative permeation amount of LID in LID-PLs group were significantly higher than those in LID-CLs group and LID-IJ group (P<0.05or P<0.01).10min,30min,1.5h,2h,4h, 6h,8h,12h,24h after administration, the main cumulative permeation amount of LID in LID-CLs group were significantly higher than those in LID-IJ group (P<0.05or P<0.01).Conclusions:The HPLC method is simple,accurate and reliable. The preparation of LID-PLs is spherical in solution, with substantially smaller mean diameter, higher encapsulation efficiency and better stability. The speed and volume of penetration of LID-PLs is higher than LID-CLs and LID-IJ, so PLs can enhance the LID transdermal activities.