Preparation And Quality Study Of Guizhifuling Transdermal Patch

Objective:By studying the extraction process of Guizhifuling prescription and formation technology and quality of Guizhifuling patch.Methods:1.Extraction process:According to the 2010 edition of pharmacopoeia to determine the content of main medicinal herbs in Guizhifuling prescription;According to the physical and chemical properties of five herbs in the prescription to determine the extraction process by referring to the relevant literature;Using the pharmacodynamics effects of the heat induced pain and acetic acid caused body distortion in mice to screen the different combination of extracts,finally the optimal combination of extracts was decided;2.Prescription screening and formation technology of Guizhifuling patch:Using single factor experiment to determine the PSA,solvent of extracts,its dosage and drug loading;The permeation characteristics was evaluated by using modified Franz diffusion cell fitted with mouse skin,and 30%ethanol-normal saline as the receptor fluid,Accumulative permeation quantities and relevant parameters of the three ingredients under different enhancers and different concentration of the enhancer were calculated.Steady permeation rates of the three ingredients as indexes to screen the optimal enhancer,and the prescription and formation technology of the patch were established;3.The study of patch quality:(1)Characters:The visual inspection of different batches of patch:Surface smoothness,bubble,permeability of the backing layer;(2)TLC identification:Choose Cinnamaldehyde,Paeonol and Paeoniflorin as indices,Cassia Twig,Cortex Moutan,Radix Paeoniae Rubra were identified by thin-layer chromatography;(3)Inspection:Inspection the adhesiveness,in vitro release and content uniformity of different batches of Guizhifuling patch;(4)Determination the content of paeoniflorin,cinnamic acid and paeonol in Guizhifuling patch by HPLC.Results:1.The extraction process:The content of paeoniflorin in Radix Paeoniae Rubra was 1.64%,the content of cinnamic acid in Cassia Twig was 0.05%,the content of paeonol in Cortex Moutan was 2.33%,RSD were 2.40%、0.77%、0.58%respectively,the content of the main medicinal herbs accorded with pharmacopoeia requirements;①The extraction process of Cassia Twig and Cortex Moutan were as follows:15 times amount of distilled water,40℃soaking for 2h and steam distillation to extract the volatile oil and aromatic water,the residues were reflux extracting 2 times for 2h and 1h each time with 15 times the amount of distilled water,concentrated solution was purified by alcohol precipitation to extract the water-soluble components;②The extraction conditions of Poria cocos were as follows:The total triterpenes reflux were extracted 2 times for 2h and 1h each time with 10 times the amount of 90%ethanol,the residues were immersion extracted 2 times for 2h and 1h each time with 10 times the amount of wardistilled water at 80℃,concentrated solution was purified by alcohol precipitation to extract the Pachyman;③The extraction process of Radix Paeoniae Rubra and semen persicae were Semen persicae reflux defatting 2 times for 1h and 0.5h by petroleum ether first,then reflux extracted with 11 times amount of 40%ethanol 2 times for 2h and 1h with Radix Paeoniae Rubra;The optimal combination of the extracts were the volatile oil in Cassia Twig and Cortex Moutan,paeonol,total triterpenes in Poria cocos,the extracts of Radix Paeoniae Rubra and semen persicae;2.Prescription screening and formation technology:The optimal formula were as follows:Duro-Tak 87-2677 as the pressure sensitive adhesive,Propylene glycol as the solvent of the extract,its dosage was half of the extracts,Drug loading was 20%,Azone as the penetration enhancer with the content of 3.0%.The optimal technical conditions were as follows:The extracts of Radix Paeoniae Rubra and semen persicae,total triterpenes in Poria cocos were dissolved by propylene glycol completely,then added Duro-Tak 87-2677,Azone,volatile oil,paeonol and stirred to mixde evenly,then used ultrasound equipment to dislodge air bubbles in the patch,after a period of time,coated on the release layer evenly and put in the air to volatilize the solvent,solidified at 40℃ for 30minutes to cross-linking,finally,covered the backing layer after cooling.Prepared Guizhifuling transdermal patch had good forming,appearance uniformity and percutaneous permeability,accumulative permeation quantities of paeoniflorin,cinnamic acid and paeonol were 163.956μg·cm-2,12.092μg·cm-2and 330.780μg·cm-2 in 24h.3.Quality study of the patch:(1)Characters:Flaky patches with brown appearance and had a delicate smell,without bubbles and permeability of the backing layer;(2)TLC identification:The TLC spots were clear,TLC qualitative identification used for transdermal Guizhifuling patch was specific;(3)Inspection:①Adhesiveness:The results of three batches of patch showed that the initial adhesion of patch were equal to No.18 steel ball and the cohesion of patch were more than 30 minutes,results indicated that the patch had proper adhesive ability;②The in vitro release of three batches of patch had good uniformity,The release mechanism of Paeoniflorin,Cinnamic acid and Paeonol in vitro coincided with Higuchi equation,the release mechanism of the patch was a skeleton controlled transdermal delivery system;③The content uniformity of Paeoniflorin,Cinnamic acid and Paeonol was well,the content uniformity of pach met the requirements of Chinese pharmacopoeia;(4)Determination of content:Established an HPLC method for the determination of paeoniflorin,cinnamic acid and paeonol in Guizhifuling patch.and the linear relationship,precision,stability,reproducibility and recovery were in line with the requirements.Conclusion:The extraction process and the formation technology of Guizhifuling patch were simple,reasonable,and feasible.The quality of Guizhifuling patch was stable and can be controlled well.