| Puerarin is an active ingredient extracted from the traditional Chinese herb Radix Pueraria lobata Ohwi and P.thomsonii Bentk, which has been widely used to treat cardiovascular and cerebrovascular diseases. Due to its poor water solubility and absorption after oral, its clinical therapeutic effect has been limited. Self-microemulsion drug delivery system(SMEDDS} is a kind of new drug delivery system, which has attract great attention in recent years. It has been used as a vehicle to increase the absorption of insoluble drugs. Therefore, puerarin was developed to self-microemulsion sustained releasing prepare, which would increase absorption and bioavailability and avoid the fluctuation of serum concentration.As model drug, Puerarin was used to be studied in the self-microemulsification delivery system. The solubility of puerarin in different oil phase, surfactant and cosurfactant was assayed. Ternary phase diagrams were constructed. The optimal prescription of SMEDDS was obtained by comparing the area of self-microemulsifying and evaluation of the resultant emulsion's appearance,which was ethyl oleate, Tween 80,PEG-400.Basis on the appearance, the droplet size after self-microemulsification, self-microemulsification time , we evaluated the quality of SMEDDS. Meanwhile,we also studied that different media and temperature and the diluted multiple had an effect on the self-emulsifying efficiency.The optimized formulation of Puerarin microemulsion was consisted of Tween80-ethyl oleate-PEG-400 at weight ratio of 45:25:30.drug concentration of Puerain microemulsion was 70mg.ml-1 .To prepare a self-emulsifying osmotic pump tablet,the following experiments were carried out. Taking advantage of mannitol, lactose at a high temperature melting but at room temperature changing solid make the self-emulsifying liquid state become solid,and then use MCC as bulking agent ,sucrose as penetrating agent to prepare osmotic pump tablet.Cellulose acetate (CA), diethyl phthalate (DEP) and polyethylene glycol 400 (PEG-400) were selected as the coating materials and acetone-isopropanol co-solvent is employed as coating medium.In this way,the puerain self-emulsifying osmotic pump tablets were prepared.Cumulative release was used to evaluate the drug release behavior of puerain in this oral osmotic pump system. Form two aspects, the dosage form and release in vitro of the puerain self-emulsifying osmotic pump tablets, selected the formulation of tablet cores and it was obtained.Sodium chloride was selected as osmotic promoting agents and its dosage was selected as osmotic promoting agents and its dosage was selected. At the same time, the effects of PEG-400(pore former) ,sucrose and coating level were respectively investigated. The results determined the dosage of DEP .The coating level and the dosage of PEG-400 and sucrose were optimized by central compositedesign design, having the accumulative release amount in 2h,6h,10h as the evaluation standard. The results showed the effect of the dosage of PEG-400 on the release rate of the puerain self-emulsifying osmotic pump tablets was stronger than that of coating level and sucrose ,the best level of the three factors was obtained. In addition, the reproducibility of the formulation and preparation process was investigated, too. The results showed the tablets with different batch number had similar release behavior in vitro. And the accumulative release amount in12h is 82.25%,their release conformed to the model of zero in10h.Put mixture of the solid SMEDDS and appropriate penetration agent into the hollow capsule shell,and prepare SMEDDS sustained-release capsule.Different sorts of penetrating agent affecting the accumulative release amount was investigated.From the investigation relust,Nacl was selected as the penetrating agent of SMEDDS sustained-release capsule. At the same time, the effects of PEG-400,sucrose and coating level were respectively investigated. The results determined the dosage of DEP .The coating level and the dosage of PEG-400 and Nacl were optimized by central compositedesign, having the accumulative release amount in 4h, 8h, 12h as the evaluation standard. The results showed the effect of the dosage of Nacl on the release rate of the puerain self-emulsifying osmotic pump tablets was stronger than that of coating level and the dosage of PEG-400,the best level of the three factors was obtained. In addition, the reproducibility of the formulation and preparation process was investigated, too. The results showed the capsules with different batch number had similar release behavior in vitro. And the accumulative release amount in12h is 92.18%,their release conformed to the model of zero in12h. |
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