| As a long-acting ester local anesthetic,tetracaine hydrochloride reversibly blocks the sodium ion channel to block the generation and conduction of nerve impulses and exert anesthesia.The NMPA database can be found that the common domestic dosage forms of tetracaine hydrochloride are tablets,glues,injections and gels.The gels are widely used in clinical applications.Tetracaine hydrochloride gel is commonly used for local anesthesia of the skin prior to venipuncture or venous intubation.However,the current domestic marketed products have a single variety and the onset time is greater than 30 minutes.Therefore,this product has a large development potential.The purpose of this study was to prepare gels with basic traits that met the requirements by optimizing the formulation and preparation process.By comparing with commercially available formulations,it was better to screen out the transdermal release and pharmacodynamic studies in vitro than commercially available formulations to investigate in the next step.Firstly,an analysis method of percutaneous permeation experimental in vitro was established.In the prescription study,the basic traits of the gel and the cumulative permeation in vitro were used as the evaluation indexes by the single factor test method,and the influence law and dosage of each excipient were preliminarily determined.On this basis,orthogonal experimental design was used to optimize the prescription.The amount of penetration enhancer,moisturizer and neutralizer was used as the independent variable.The cumulative permeation and permeation rate in the percutaneous permeation test were used as evaluation indexes,and after verification,the most excellent prescription of tetracaine hydrochloride gel was finally determined.In the preparation process research,the swelling mode of the gel matrix,the order of addition of the auxiliary materials,and the influence of the mixing method on the basic properties of the gel were investigated.The appearance,viscosity,spreadability and ease of process operation were used as evaluation indexes.A preferred preparation process has been determined.The quality analysis method of tetracaine hydrochloride gel was established by high performance liquid chromatography(HPLC),including content determination and related substance analysis methods,and the method was verified.The results showed that the method has high sensitivity and the concentration of tetracaine hydrochloride has good linear relationship in the range of 0.2-80μg/mL(R~2=0.9998),the method is simple and easy and has high accuracy,good the precision.And in the methodological verification of the related substances,the results show that the blank excipients and the solvent do not interfere with the determination of impurities.The specificity is good,and the resolution of degradation products produced under the conditions of forced destruction and the main peak of tetracaine hydrochloride meets the requirements,so the method can be used for the quality analysis of tetracaine hydrochloride gel.The stability of the preparation was investigated by a stability test,and three batches of samples were prepared according to the optimized prescription and process,and were packaged with the listed hose,and then carried out the influencing factors experiment(high temperature,high humidity,light),accelerated test and long-term test.During the observation period,there were no significant changes in the appearance,pH,content,and related substances of the samples,which met the requirements.In summary,tetracaine hydrochloride gel which was prepared by prescription has simple preparation process and is easy to operate,controllable and stable.And in vitro percutaneous penetration and pharmacodynamic test compared with commercially available preparations,the optimized prescription has been significantly improved and achieved the intended purpose. |
