Study On Quality Of Ginkgo Leaves And Improvement Of Preparation Technology

Ginkgo Biloba is a unique tree growing in China and has been used pharmaceutically for a long history. According to Compendium ofMateria Medica, it is a little sweet but also bitter and astringent, having the effect of relieving asthma and reducing urination and other kidney and lung related diseases. Ginko Biloba is usually extracted and processed into various kinds of formμlations for the treatment of coronary heart disease, angina and hypertention, etc. China is rich in Ginko Biloba sources, about 70%of which in the world are cμltivated in China. Annually up to 20 million kg of Ginko Biloba leaf are harvested, providing the majority of raw material of foreign Ginko Biloba products.Ginkgo biloba tablet is currently one of the Chinese medicines with the highest sales. There are more than 100 manufacturers producing and selling this product, with annual sales of more than 2 billion yuan. However, compared with similar products in Germany and France, the existing domestic Ginkgo biloba tablets still have the problem of low efficacy, quality instability and so on. The quality and clinic effect of Ginkgo Biloba products from different manufacturers differ greatly; even different batches produced by the same manufacturers have significant difference in the product quality. Therefore, with guaranteed supply of stable and high quality raw material, the optimization of excipients and formμlation technology has become a decisive factor for the quality of Ginkgo Biloba Tablets. To further discuss this problem, the quality of Ginko Biloba tablets from home and abroad was compared. Also the difference among Ginkgo Biloba tablets produced with different excipients and pharmaceutical technology was researched.In this paper, a method was established to evaluate the quality of Ginkgo biloba tablets from home and abroad, including UV spectrophotometric and HPLC for the determination of dissolution, a major indicator for the quality of Ginkgo biloba tablets. With the same Ginkgo biloba leaf extract as the raw material, ten formulations for the preparation of Ginkgo biloba tablets were devised using powder direct compression technique. Ten different lactoses, sodium carboxymethyl starch, silica powder, and magnesiμm stearate were selected as the excipients. Compared with Ginkgo biloba tablets produced by Tebonin of Schwabe of Germany and a pharmaceutical company in Shanghai(X Company), their quality was studied and the best formμlation was separated.Results showed that 1) Quality instability has been an apparent defect for domestic Ginkgo biloba tablets; the total flavonoides content, the disintegration time limited and dissolution profiles of Ginkgo biloba tablets differed greatly among products either from different manufactures or the same batch of the same manufacture.2) Through quality analysis for tablets prepared from the 10 formulations using powder direct compress technique, formulation which used Ludipress as the excipent exhibited a similar dissolution profile with that of tablets from Tebonin and X company. Besides, the tablets quality prepared from this formulation was qualified. Therefore, this formulation was considered to be the most optimal.Wet granule comprssion technique was also utilized for the preparation of Ginkgo biloba tablets. Comparison of tablets quality between two techniques was made. Results demonstrated that Ginkgo biloba tablets prepared from all six formμlations were qualified. However, the similarity factor (f2) showed that only one formulation’s dissolution profile (formulation No.11) was similar to that of tablets produced by Tebonin and the X Company.To perform bioequivalence study between the self-made Ginkgo biloba tablets and tablets form Tebonin and X Company, HPLC-MS method was established for the determination of Ginkgolides in the plasma samples collected from Beagle dogs. The result showed that the pharmacokinetics of Ginkgolides A and B, and bilobalide fitted one-apartment model after the administration of self-made Ginkgo biloba tablets and tablets form Tebonin and X Company.(1) Compared with Ginkgo biloba tablets on the abroad market, the AUC(0-∞) of Ginkgolides A of self-made Ginkgo biloba tablets was basically the same while the Tmax was remarkably shortened given the same dosage. Meanwhile, the AUC(0-∞) of both Ginkgolides B and bilobalide were also significantly improved with basically unchanged Tmax. The AUC(0-∞) of Ginkgolides A, Ginkgolides B and bilobalide as a whole was increased by 1.3 folds.(2) In comparison with Ginkgo biloba tablets on domestic market, the AUC(0-∞) of Ginkgolides A of self-made Ginkgo biloba tablets was much more higher while the Tmax was basically unchanged given the same dosage. Meanwhile, the AUC(0-∞) of Ginkgolides B was five times as high as that of domestic tablets while the Tmax was extended by five times. The AUC(0-∞)of bilobalide was improved by 1.4 times with essentially unaltered Tmax The AUC(0-∞) of Ginkgolides A, Ginkgolides B and bilobalide as a whole was increased by 1.9 times.Accordingly, either based on the single component analysis or the overall analysis of three components, the AUC(0-∞) of self-made Ginkgo biloba tablets was significantly improved, demonstrating the feasibility of its formulation techniques. As revealed by the result of two sides of single test (TOST) and (1-2α)% Confidential Interval analysis, the self-made Ginkgo biloba tablets and products from home and abroad were inbioequivalent. Contributing reasons may include,1) the fast release of drugs from the self-made Ginkgo biloba tablets, which increased the drug absorption and bioavailability; 2) differences in the absorption and metabolism extent of the three components as a whole among three products; and 3) larger individual variability as shown by ANOVA analysis(P<0.05).Based on studies on the quality of Ginkgo biloba tablets from different soures, on the excipients and direct compression techniques for Ginkgo biloba extracted powder, and on the influence of different formulation techniques on tablets’quality and bioavailability, Ginkgo biloba tablets was prepared from direct power compression technique in this study. According to the above results, the self-made Ginkgo biloba tablets possessed stable quality, similar dissolution profile with public acknowledged Tebonin, Ginkgo biloba tablets from Schwabe, German, and remarkably improved bioavailability.