Studys On Shuxiong Sustained-release Pellets

Shuxiong tablets has been proved effective to treatment of coronary disease, due tocoronary disease must take medicine for a long time, but traditional Chinese medicinepreparations have lots of disadvantages, such as outdated dosage forms, backwardtechniques, inconvenience for patients' intake, too many daily intake times and highlydosage, which have interfered the development of TCM. In order to meet the need ofmodernization of Chinese herb preparation and speed up the movement toward the world,the present study was designed to develop sustained-release pellets of Shuxiong formula.This project aimed at the clinic characteristic and property of the effective part,systematically studied the extraction, separation, purification, forming procedure andpharmacokinetics, as a result, a high-quality sustained-release pellets had been made, andalso found a methodological system for evaluation the research and development ofsustained-release preparation of Chinese traditional medicine.UV methods were used to determination the contents of Panax notogisengsaponins(PNS) and safflor yellow(SY); the studies were done on the release characteristicsof the three target compositions, ginsenoside Rg₁, hydroxysafflor yellow A(SHYA) andferulaic acid(FA) which with different physicochemical quality. It is established that thequantitative methods of the three target compositions quantity in preparation, release degreein dissolution medium and the blood drug level of FA in rabbit plasma. The establishedmethods above and the study on the target compositions in different excipient preparationslaid a foundation for studying preparation technology and pharmacokinetics in vivo ofsustained-release Shuxiong pellets.Taking the contents of effective components or parts as the evaluation indexes, thefactors such as heating temperature, decoction time, alcohol concentration which wasinfluenced on the extraction were investigated, based on the mono-factorial test, useorthogonal test or uniform test to optimizing the best extract and purification process. RootPanax notoginseng was added 12 times amount of 75% alcohol, extraction two times, 0.5 heach time. The extraction ratio of PNS was above 95%; with the technique of macroporousresin, the PNS was purified with macroporous resin HPD100, the total saponins contentwas 65.0%, the yield of extracta sicca is about 8.85%. Carthamus tinctorius L. was added 14 times water, soaked at 75℃water-bath for 2 times,1 hour per time, the extraction ratioof SY was about 87%, the SY was purified with macroporous resin HPD400, the total SYcontent was 23.0%, yield of extracta sicca was about 8.0%. Ligusticum chuanxiong Hortwas added 10 times 55% alcohol, extraction 2 times, 1.0 h each time, the extraction ratio ofFA was above 95%, the yield of extracta sicca was about 20%. The study on thepharmacodynamics indicated that compound Shuxiong extracts could evidently nullifiedthe pituitrin-induced Electrocardiographic ischemia ST-T (P＜0.05) as compared withcontrol group. There was no significant difference (P＞0.05) between Shuxiong Ex andShuxiong tablets. It seems that majority of effective constituents of Shuxiong tablets werestill retained in Ex, and the preparation processes for Shuxiong Ex were proper andpracticable.Rolling into ball methods were used to prepare Shuxiong plain pellets, based on themono-factorial test, the prescription of forming process was seek optimum according toorthogonal design. Four factors (the quantity of microcrystalline cellulose, adhesive type,rolling time and rolling speed), nine levels of each variable were selected to planexperiment. After experimental examing, the ingredients in selective prescription were asfollows: MCC: Ex (1:1), the rolling speed of coating pan was 40rpm, angle of elevationwas 35°, adhesive was 2% HPMC dissolve in 70% alcohol, rolling time was 50min,resultdisplay this prescription could achieve the designed demands.Take the release rate as the investigate index, the factors such as coating materials,anti-tacking gents, plasticizer, quantity of PVPK30,coating level and coating temperaturewhich was influenced on the release were investigated. Based on the mono-factorial test,the prescription of coating solution was seeked.optimum according to uniform design.Three factors (the proportion of RS/RL, coating level and quantity of PVPK30), nine levelsof each variable were choose to plan experiment. After experimental exam, the ingredientsin selective prescription were as follows: the proportion of Eudragit RL/RS was 1:8,quantity of talc powder was 60% of the quantity of polymer, quantity of DEP was 18%,quantity of PVPK30 was 8%,the percentage increased in coating materials weight was16.5%. The sustained-release Shuxiong pellets coated by this kind of coating solution couldachieve the designed demands. The description of dissolution profiles suggested that amongthe different kinetics, the weibull-order became the most appropriate model to describerelease kinetics of Rgl and FA, Higuchi-order most suit for HSYA. Results also display thedissolution characteristic of those there ingredient was no significant difference (f＞50).According to the sustained-released and controlled-release preparation guidance in"Chinese pharmacopoeia"2005 edition 2nd part (appendixâ…©â… â…©D) and requirements under capsule items in 1st part (appendix I A), TLC was adopted to distinguish PNS, SY,Ligusticum chuanxiong Hort., HPLC method has been adopted to measure the content ofginsenoside Rg₁, HSYA and FA, content limits can't below 1.1%, 0.4%and 0.08%homologous. Meanwhile, the in vitro dissolution also been measured. Other regularexaminations related to pellets have also been done. The results indicate that the quality ofthis pellet is stable and controllable.The concentration of FA in dog plasma after a single oral administration of theShuxiong sustained-release pellets was detected with compound Shuxiong extracts ascontrol group. The result indicated that FA fits the two-compartment. Results shows that thearea under curve have no significant different (P＞0.05), t_1/2β,C_max,T_peak and MRT all havesignificant different(P＜0.01),the evaluation result showed that AUC is bioequivalent, butC_max, T_peak are beyond the confine, the C_max are smaller by contrast with the ordinary tablet,but the T_peak is prolonged.the sustained-release tablet has the characteristic ofsustained-release and the result comes to the purpose of the paper design.The innovation points in this article are as follows: Macroporous absorbing resinHPD400 has been firstly used in purification SY, bonding with freeze-dried to prepare thetotal SY extracta sicca. Multi- ingredient release synergism in dissolution medium wasfirstly used as index to optimizing prescription and technology parameter of compoundsustained release preparation of Chinese medicine. Systematic explored a new researchmode of compound sustained release preparation of traditional Chinese medicine, the modeis bonding use the methods of screening and preparation of effective part, procedure studyof sustained-release preparation, combination evaluation of sustained release effect. Theseprovide a scientific basis for further research on sustained release Chinese medicinepreparation.