Preclinical Pharmaceutical Research Of NFS Spray Film-transdermal Absorption Preparation

Objective: To study on the preclinical pharmacy of NFS spray film-transdermal absorption,including re-evaluation of quality standard of original medicinal materials,preparation technology,quality standard,skin irritation and stability.Methods:(1)HPLC and UV fingerprint are used to establish the quality control method of Erythrinae Cortex.The content of germacron is increased to determine the quality standard of Wenyujin Rhizoma Concisum.(2)The process optimization of the preparation methods of Qingfeng vine,Corydalis,Erythrinae Cortex and Rhizoma Wenyujin Concisum are carried out by star point design-response surface method and orthogonal design.Taking the amount of volatilization,film formation time,film properties and content uniformity as indicators,the orthogonal design is used to determine the amount and ratio of filming auxiliary materials.Based on the cumulative release of the indicator component sinomenine,the star-point design-response surface method is used to determine the type and amount of penetration enhancer.(3)The identification of intermediate traits,qualitative identification of thin layers,determination of content,and related inspection items are studied to establish quality standards for NFS intermediates.The NFS spray agent identification,thin layer identification,pH value and content determination are studied to establish the quality standard of NFS spray agent.(4)The skin irritation response of the NFS spray are determined by experimental rabbits to determine the skin irritation of the NFS spray.(5)Influencing factor test,accelerated test,and long-term sample retention test are studied to determine the stability of the NFS spray agent.Results:(1)The HPLC and UV fingerprint methods were established and verified.The results of the two methods were consistent.The content of germacron in Wenyujin Rhizoma Concisum should not be less than 0.027%.(2)The best process of Qingfeng vine,Corydalis,and Erythrinae Cortex is 8 times of 50% ethanol extraction for 3 times,40 min each time.The best extraction process of Wenyujin Rhizoma Concisum is 60% ethanol percolation,the flow rate is 3 mL/min,and 8 times of the percolation solution is collected.The best film-forming prescription is 2% PVP and 1% PVA.The best transdermal formulation is 3.8% hydroxypropyl-?-cyclodextrin and 4.9% propylene glycol.(3)The TLC identification of Qingfeng vine and Corydalis of intermediate 1 is strong,and the content of sinomenine should not be lower than 21.69 mg/g.The content of germacron in intermediate 2 should not be lower than 464.32 ?g/g.The NFS spray film has strong specificity for the identification of Qingfeng vine,Corydalis and Wenyujin Rhizoma Concisum.The pH range is 4.07~6.11,the sinomenine content should not be lower than 1.05 mg/mL,and film forming time should not exceed 215 s.(4)The skin irritation test show that the blank excipients and liquid medicine do not cause erythema redness and swelling on the skin.(5)In the study of the influencing factors in the stability study,under the conditions of high temperature and light removal packaging,ethanol and water are volatile,resulting in large deviation of the loading,but no effect on the traits,pH value and thin layer identification.Conclusion: In this study,the preclinical pharmacy of NFS Spray-film transdermal absorbent was studied through the re-evaluation of the quality standard of the original medicinal materials,preparation technology,quality standard,skin irritation and stability,which laid a foundation for the development of new formulations of traditional Chinese medicine.