| OBJECTIVE: To optimize the preprative technique of ginkgo-phospholipid complex, develop release tables for ginkgo-phospholipid complex and its quality criteria, and inspect the initial stability and pharmacokinetics of the release tables..METHODS:①Preparation of ginkgo-phospholipid complex: To obtain appropriate percentage of extract of ginkgo biloba and phospholipid, to dissolve organic solvent, to get the depurated ginkgo-phospholipid complexa after baking drying under reduced pressure. It was based on the complexing rate of ginkgo-phospholipid complex calculated from the ratio of the content of flavon in ginkgo-phospholipid complex. To optimize the preprative technique of ginkgo-phospholipid complex by orthogonal design in the base of single factor investigation by UV and use complexing rate as control article. Ginkgo-phospholipid complex powder was baking drying under reduced pressure.②Preparation of ginkgo-phospholipid complex release tables: The material of delayed release and filler preliminary screening though investigating appearance, process of preparation, dissolution rate. To optimize the formula by orthogonal design through the dissolution rate of 12h.③Quality criteria of ginkgo-phospholipid complex release tables: The ginkgo flavone was identified by TLC. Content of ginkgo flavone, dissolution rate and breakdown test were determined by HPLC. The characteristics, water content and microorganism limit of ginkgo-phospholipid complex release tables were desire by pharmacopoeia of People's Republic of China.④Initial stability investigation: It was based on characteristics, dissolution rate, content and related substance to investigation the influential of temperature, humidity and illumination to ginkgo-phospholipid complex release tables in influential factor experiment.⑤Pharmacokinetics study: To contrast the pharmacokinetics of ginkgo compressed tablets and ginkgo-phospholipid complex release tables in vivo of SD rats.RESULTS:①Preparation of ginkgo-phospholipid complex: It based on which flavonoids of ginkgo-phospholipid complex could react with aluminum chloride, determined the absorption value at the wavelength of 273 nm by UV. In this method, the linear range was from 0 to 22μg/ml, the relevant coefficient are 0.9998. The average recoveries of samples were between 98.8%～104.2%,RSD =2.97%(n=9).The complexing rate can be used for quantitation of ginkgo-phospholipid complex. The optimized preparation was obtained as follows: Taking EGB 15g, dissolved in tetrahydrofuran 1000ml adding soybean phospholipid 15g, heat while stirring 55℃, reaction 20 hours, vacuum steam addition to solvents, vacuum drying, add 500ml of dichloromethane, sealed and stir for 1 hour, plus diatomaceous earth filtration adsorption, vacuum to remove inert solvent, vacuum drying again, the product is purified ginkgo-phospholipid complex.②Preparation of ginkgo-phospholipid complex release tables: According to the preliminary release material with filler screening results, use HPMC (K100cp) as sustained release material, microcrystalline cellulose as a filler, with optimization for ginkgo-phospholipid complex release tablets process for the HPMC (K100cp) 20%, silica powder 4%, 30%microcrystalline cellulose, magnesium stearate as lubricant, 70% ethanol as adhesive to wet granulation tabletting method, made from sustained-release tablets.③Quality criteria of ginkgo-phospholipid complex release tables: Ethyl acetate-methyl ethyl ketone-methanol- water (5:3:1:1) as developing agent, 3% aluminum chloride ethanol solution as the color reagent, TLC identification of flavonoids of ginkgo biloba. HPLC with methanol: 0.4% phosphoric acid (65:35) as mobile phase, detection wavelength 360nm, measured content of flavonoids of ginkgo-phospholipid complex release tables and related substances, the establishment of the determination method is accurate, sensitive, and accessories on the determination of non-interference. The characteristics, water and microbial limit of ginkgo-phospholipid complex release tables into the examination also meet pharmacopoeia requirements.④Initial stability investigation: Factors results showed that the product temperature at 60℃, relative humidity of 92.5% under the conditions of high humidity and light stability; so product can be stored at room temperature; accelerated test results are stable, that this drug has a predictable period at room temperature for two years; long-term 12-month test results show that the stability of the product. Long-term tests are still continuing.⑤Pharmacokinetics study: Ginkgo-phospholipid complex release tables and Ginkgo biloba extract in normal rats in vivo pharmacokinetic, indicating that sustained release tablets significantly increased the maximum plasma concentration, plasma time-time area under the curve was significantly increased, indicating ginkgo-phospholipid complex release tables can significantly improve the bioavailability of drugsCONCLUSION: Established medicinal preparation, simple and the high content of main ingredients in ginkgo-phospholipid complex release tables; the prescription of ginkgo-phospholipid complex release tables is reasonable, preparation process is stable, the quality is stable and controllable, with good prospects for the development and application.
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