Preparation And In Vitro Transdermal Study Of Two Transdermal Drug Delivery Preparations For Fruits Of Capparis Spinosa L.

Objective:To evaluate the quality for fruits of Capparis Spinosa L.in different growth stages.Prepare two transdermal drug delivery preparations for fruits of Capparis Spinosa L.and study their in vitro transdermal properties.Methods:1.The Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System(2012 Edition)was used to establish the HPLC fingerprints of 14 batches for fruits of Capparis Spinosa L.with different growth stages and analyze the similarity.Cluster analysis,principal component analysis,and partial least squares-discriminant analysis(PLS-DA)were performed using SPSS 25.0 and SIMCA-P 14.1 software.Chemical compositions are identified by comparison of controls and the contents in the sample are determined.2.Box-Behnken design-response surface methodology was used to optimize the optimal matrix of the ointment,the dosage of penetration enhancer in the preparation was screened by in vitro permeation test and HPLC with stachydrine hydrochloride as the index.3.The formula of gel was determined by single factor experiment,the dosage of penetration enhancer in the preparation was screened by in vitro permeation test and HPLC method with stachydrine hydrochloride as the index.4.Exploring the in vitro transdermal pattern and experimental parameters of stachydrine hydrochloride in two transdermal drug delivery preparations through in vitro permeation test.UPLC-MS/MS technology was used to study and compare chemical components of two transdermal drug delivery preparations before and after transdermal delivery.Results:1.A total of 14 common peaks were matched by the HPLC fingerprint of 14 batches for fruits of Capparis Spinosa L.,and peak 2 was identified as protocatechuic acid,peak 13 as rutin,and peak 14 as kaempferol-3-O-rutinoside,and the fingerprint similarity range was 0.933 to 0.990.Cluster analysis divided 14 batches for fruits of Capparis Spinosa L.into four categories.Principal component analysis showed that the quality of ripe for fruits of Capparis Spinosa L.was better.Nine differentiated components,including rutin and kaempferol-3-O-rutinoside,were screened by PLS-DA analysis.The contents of protocatechuic acid,rutin,kaempferol-3-O-rutinoside and stachydrine hydrochloride were0.0323-0.0594 mg/g,0.1157-0.4640 mg/g,0.0629-0.3307 mg/g,33.2686-66.7430 mg/g.2.The matrix type of the ointment is O/W type.Optimization of three factors that have a significant impact on ointment molding using response surface methodology.The optimal matrix ratio is sodium dodecyl sulfate-propanediol-RH40(0.46:14.62:10.00),the drug loading is 10%,and the amount of penetration enhancer in the ointment is 2%for the in vitro permeation test.3.The matrix of gel is Carbopol 980NF,the dosage is 1.2%,the p H regulator is Triethanolamine,the dosage of propylene glycol is 12%,the drug loading is10%,and the dosage of penetration enhancer in gel is 3%for in vitro permeation test.4.The in vitro transdermal pattern of stachydrine hydrochloride in ointment conforms to the first-order kinetic equation,and the cumulative penetration amount per unit area in 24hours is 2934.1192μg/cm~2,skin penetration rate is 0.2516μg/cm~2/h,the cumulative penetration rate is 79.0425%,the drug residue rate is 4.4696%,the intradermal retention rate is 0.2653%,and the loss rate is 16.2226%.In vitro transdermal pattern of stachydrine hydrochloride in gel conforms to the first-order kinetic equation,and the cumulative penetration amount per unit area in 24 hours is 3308.4727μg/cm~2,skin penetration rate is0.1746μg/cm~2/h,the cumulative penetration rate is 90.1289%,the drug residue rate is0.5483%,the intradermal retention rate is 0.2380%,and the loss rate is 9.0848%.UPLC-MS/MS chemical composition analysis showed that stachydrine,rutin,quercetin and other chemical components can be detected in the skin penetrating receptor solution of Capparis Spinosa L.ointment and gel..Conclusion:1.The established HPLC fingerprint for fruits of Capparis Spinosa L.is easy to operate and the results are reliable,and protocatechuic acid,rutin and kaempferol-3-O-rutinoside and stachydrine hydrochloride can be used as indicator components for the quality evaluation for fruits of Capparis Spinosa L..2.The preparation processes of Capparis Spinosa L.ointment and gel are stable and reliable,with slow release effect,which can extend the efficacy time to a certain extent.3.The In vitro transdermal patterns of Capparis Spinosa L.ointment and gel conform to the first-order kinetic equation,and the chemical components such as stachydrine,rutin,quercetin,etc.may play an anti-inflammatory role through the skin.