Study On Preparation Technology And Quality Standard Of Compound Cortex Fraxini Tablets

Compound Cortex Fraxini Tablets are made according to a new prescription in order to solve some questions like preparation technology, quality standard, raw materials source of Cortex Fraxini Bone Capsule (WS-10901(ZD-0901)-2002) and Bawei Cortex Fraxini Pills (WS3-BC-0238-95). The new tablets consist of 5 herbs, namely Cortex Fraxini, Meconopsis Horridula, Pyrethrum Tatsienense, Dragon Bone and Calcite Calcitum,and they are used for the promotion of blood circulation, treatment of broken bones, relieving of the pain, treatment grasserie. It can be used in the treatment of pain in joints, pain and swelling from sprain caused by diseased hot "gangba". "grasserie" as described by Tibetan doctors, which is described by traditional Chinese doctors as rheumatoid arthritis, acute and chronic torsion contusion, and so on. Cortex Fraxini Bone Capsule and Bawei Cortex Fraxini Pills are made from raw materials and hence good in treatment effect, but they have the disadvantages of low bioavailability and slowly-working,and ti usually takes a long time for the pills to disintegrate. Some herbs in Bawei Cortex Fraxini Pills are greatly influenced by seasons and environmental factors, which results in deficient resources, or their turning to toxic medicinal materials, and therefore their clinical uses are affected.For all this, we are considering promoting the Tibetan medicine and benefitting all mankind as the mission, and under the guidance of traditional Tibetan medicine theory, we word on the remixing prescription, the applying of modern pharmaceutical technology, the extracting and refining according to the physicochemical properties of active components from herbs, and the producing of tablets on the basis of the properties of extracts and production reality. Extraction process was enlarged by pilot-plant instruments, investigating the process stability of product, drafting the quality standard, and carrying on the preliminary stability test, and verifing the operability of product process and the stability and controllabity of preparation quality.The paper consists of three parts, preparation technology, drafting of quality standard, and stability tests.The first part is the study on preparation technology. The water extraction process of Cortex Fraxini and the ethanol extraction process of Meconopsis Horridula and Pyrethrum Tatsienense were investigated respectively by orthogonal experiment design, according to theproperties of herbs. The water extraction process of Cortex Fraxini was optimized by considering the sum of aesculin and aesculetin content as investigation targets and taking extract rate into consideration as well. The ethanol extraction process of Meconopsis Horridula and Pyrethrum Tatsienense was optimized by considering the sum of total flavonoids content and extract rate as investigation targets.Dragon Bone and Calcite Calcitum were crushed to powder, and they were employed as supplementary materials in the preparation of tablets, which reduced the use of supplementary materials, reduced the cost, reduced the dose, and improved the compliance of patients. The preparation technology of product was as follows:water extractingtwice for Cortex Fraxini with 6 times the amount of water for each extraction, obtaining extract of 60min, the extract was concentrated into each 2mL of 1g Cortex Fraxini medicinal materials under reduced pressure at 80℃, Centrifuged for (10000rpm) 5min, taked the supernatant continue to concentrate and dry, the dry paste was crushed into powder, reserve supply; 70% ethanol extract 2 times for Cortex Fraxini,10 times the amount of 70% ethanol for esch, extraction of 90min, the extract was concentrated under reduced pressure at 70℃ and the ethanol was recoved to no ethanol taste, continue to concentrate and dry, the dry paste was crushed into powder, reserve supply; Dragon Bone and Calcite Calcitum were separately crushed to powder, mixing uniformly together with water extract dry power, ethanol extract dry power, starch, microcrystalline cellulose, adding appropriate amount of 80% ethanol into soft material, granulated by 14 mesh, dried at 60℃, granulated again by 14 mesh, adding magnesium stearate, mixing, tabletting, coating film, i.e.The second part is about the drafting of the quality standard. Taking Chinese Pharmacopoeia(Volume One) in 2010 as a guide, we draft the draft of quality standardfor Compound Cortex Fraxini Tablets. The TLC identification method ofMeconopsis Horridula and Pyrethrum Tatsienense in Compound Cortex Fraxini Tablets was established, the HPLC determination method ofaesculin and aesculetin content in Compound Cortex Fraxini Tablets was established, and its methodology was investigated. This product’s content limitation was made according to Cortex Fraxini content limitation of Chinese Pharmacopoeia(Volume One) in 2010. The results proved that the method of TLC identification of Meconopsis Horridula and Pyrethrum Tatsienense in Compound Cortex Fraxini Tablets was simple and specific. that the calibration curve of aesculin was linear in the range of 20.9μg/mL～ 167.2μg/mL. the calibration curve of aesculetin was linear in the range of 9.9μg/mL～79.2μg/mL. the RSD% of the Repeatability was 1.54%. the average recovery of aesculin was 98.52%. the RSD 1.03%. the aesculetin 98.08%. and the RSD% 1.53%. the test solution was stable within 24h, accessories and negative sample were undisturbed for the determination of the test sample, which indicates that the method is specificand accurate, and that the sum of aesculin (C15H16O9) and aesculetin (C9H6O4) content determines that of Cortex Fraxini in each tablet and it should not be less than 2.0mg.The third part is thestability tests. The accelerated stability and long-term stability of this product had been investigated according tolegal requirements of Pharmaceutical Administration Law and Regulations for the Registration and Management of Drugsand the draft of quality standard of Compound Cortex Fraxini Tablets. Results showed that, after 6 months accelerated stability test, the products have met the provisions of the draft ofquality standard, and have been stable after the eighteen-month long-term stability tests.At last, we draw the conclusion that the prescription of Compound Cortex Fraxini Tablets is reasonable by using modern preparation technology, the technology is stable, the quality of the product is guaranteed by the improved quality standard, the preparation has fine stability, which providessafe and reliable preparation for clinics, brings good news for rheumatism arthritis patients, and has a broad prospect of clinical application.