| Objective:The preparation and evaluation of the transdermal patch of Bitong patch, a skeleton-controlled TDDS was developed.lt is a basis for the development of the transdermal patch of Bitong through studying on its extraction process, molding process, the quality of preparation standards.Methods:1The extraction technology research:①To optimize the conditions of extraction technology of the volatile oil in the transdermal patch of Bitong by steam distillation. The L9(34) orthogonal design experiments were carried out, in which three influence factors, soaking time, amount of water and extraction time were selected, and the rate of volatile oil extracted were regarded as the evaluating indices.②L9(34)table of orthogonal test was used to optimize the extraction process with alcohol concentration, alcohol quantity, extraction time and extraction number as the investigate factors, the content of osthole, dried cream yield as the indexes, to analyze the data of the technological condition of ethanol refluxing of dregs after Mentioning volatile oil and Radix Angelicae Pubescentis, Myrrh, Olibanum and other drugs in Prescription by Comprehensive Evaluation of Multiple marks.③Purified study on obtained decoction of the extraction of volatile oil. To optimize the conditions of Purification process of the obtained decoction of the extraction of volatile oil by Ethanol precipitation. The L9(34) orthogonal design experiments were carried out, in which two influence factors, the mass concentration of the initial liquid, the ethanol concentration of liquid and Alcohol precipitation time were selected, and the content of Ferulic acid, dried cream yield were regarded as the evaluating indices.2The molding technology research:L9(34)table of orthogonal test was used to optimize the Preparation process with Eudragit RL100, the amount of dibutyl sebacate, the amount of lanolin and the amount of Succinic acid as the examine factors, the appearance, initial adhesive, sustained adhesive as the indexes, to analyze the data of the technological condition of preparation process of the transdermal patch of Bitong patch by Comprehensive Evaluation of Multiple marks.3The quality standard research:It was identified for Radix Angelicae Pubescentis, Rhizoma Ligustici Chuanxiong, Foeniculum vulgare, Cortex Cinnamomi, Radix Dolomiaeae, Boswellia carteri, Myrrha, Borneolum Syntheticum by TLC. According to related regulations in China Pharmacopoeia, It was checked the appearance,Ointment content, heat resisting property, shaped property, adhesive ability(including initial adhesive, sustained adhesive and peeling strength), weight difference of the transdermal patch of Bitong patch; As indicators of the quality control, the content of osthole and the content of columbianadin was determined by HPLC, in which the chromatography conditions were that the samples were separated at30℃on a ChromstarTM C18(4.6×250mm,5μm)column eluted with acetonitrile-water(60:40)as the mobile phase, Flow rate was set at1.0ml.min-1, the detection wavelength was set at330nm and injection volume was set at10ul. The number of theoretical plates columbianadin should be not less than5,000. According to the third method of determination of release in theAppendix X D of the second department of China Pharmacopoeia, It carry out the release test of the transdermal patch of Bitong patch by the second method of Determination of Dissolution(paddle method) device. cumulative percentage release based on the content of osthole by HPLC was used to evaluate the release of the transdermal patch of Bitong patch.Results:1optimization of extraction process:①The optimium conditions for the extraction technology of volatile oil for the transdermal patch of Bitong patch was that no soaking time, amount of water was10times of medicinal materials, and extraction time was8hours and average extraction rate of volatile oil was0.643%.②The optimum technological conditions of the ethanol refluxing extraction for the transdermal patch of Bitong patch was as follows:the70%ethanol extracted2times, one hour at a time, first, plus the amount of alcohol8times, the second plus the amount of alcohol to6times. Test results were as follows:the average of extract yield was24.93%, the average content of osthole was5.49mg/g per-post.③The best purification process for the transdermal patch of Bitong patch was that the mass concentration of the initial liquid was1.0to1.10g/ml, the ethanol concentration of liquid was70%, and the liquid placed in the refrigerator (5℃) for12hours. Test results were as follows:the average of dried cream yield was16.12%, the average content of Ferulic acid was2.27mg.2optimization of molding technology:The amount of pressure-sensitive Eudragit RL100was2.0g, the amount of dibutyl sebacate was0.8g, the amount of lanolin was0.14g, and the amount of Succinic acid was0.12g, Per100cm2in the transdermal patch of Bitong patch. Prepared transdermal patches showed paste surface is smooth, Paste is uniform and the color were the same for eachpart of paste; the result of initial adhesive test was13to14ball can be sticked, the result of sustained adhesive test was displacement is less than2mm with hanging5g weights within24hours. Above-mentioned results Indicates that the extraction process is stable and feasible.3The quality standard of the transdermal patch of Bitong patch:It was simple for the methods to identify Radix Angelicae Pubescentis, Rhizoma Ligustici Chuanxiong, Foeniculum vulgare, Cortex Cinnamomi, Radix Dolomiaeae, Boswellia carteri, Myrrha, Borneolum Syntheticum and so on in the transdermal patch of Bitong patch by TLC; the spots were clear on the TLC pictures; the negative contrasts were not disturbed. The items of the transdermal patch of Bitong patch, appearance,ointment content, heat resisting property, shaped property, adhesive ability(including initial adhesive, sustained adhesive and peeling strength), weight difference were accord with the regulations of China Pharmacopoeia. Injection volume of osthole showed a good linear relation in the range of0.149-1.192μ(r=1.0), precision(RSD) were0.83%, average contents of osthole was0.785μg(RSD)=2.21%) in the reproducibility experiments, the average recovery was97.17%with RSD of0.24%(n=6). The contents of osthole in three batches were3.940mg,3.893mg,3.876mg,the average contents was3.903mg. Injection volume of Columbianadin showed a good linear relation in the range of0.054-0.432μg(r=1.0), precision(RSD) were0.65%, average contents of Columbianadin was0.109μg(RSD=2.77%) in the reproducibility experiments, the average recovery was95.98%with RSD of0.77%(n=6). The contents of Columbianadin in three batches were0.5873mg,0.5825mg,0.5914mg, the average contents was0.5871mg. The release research of the transdermal patch of Bitong patch was as follows:cumulative release percentage of osthole in30%ethanol solution was96.26%in24h.Conclusion:The transdermal patch of Bitong patch Prepared has many advantages, as follow: extract pharmaceutical ingredients completely, has excellent adhesive strength, compatibility of creams and matrix is good, release properties is well, and provide a reference for the study of Chinese herbal compound transdermal patch. |
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