| The tuber of Alisma orientalis (Sam.) Juzep. (Alismataceae) is a traditional Chinese crude drug under the name of Zexie. It has anti-hyperlipidemia, anti-atherosclerosis and anti-fatty liver activities and the effective constituents are the compounds named alisol, which are triterpenoids and lipophilic. But because of their hydrophobic property, the active ingredients have a low absorption and low bioavailability after oral administration. Self-emulsifying drug delivery system (SEDDS), which is well known for its potential to improve the aqueous solubility and oral absorption of lipophilic drugs, are comprised of isotropic mixtures of oils, surfactants and co-surfactants and could spontaneously emulsify when exposed to the fluids of the gastrointestinal tract to form oil-in-water emulsions or microemulsions. So far there have been many marketed formulations of SEDDS in the world. Thus, in order to improve the solubility and bioavailability of the effective constituents of Alisma orientalis, we have developed a SEDDS formulation of the total terpenoids from Alisma orientalis.1 the physicochemical properties of extract from Alisma Orientalis by supercritical carbon dioxide extractionThe supercritical CO2 extract from Alisma orientalis is oil-like substance, and has a high content of active ingredient and was convenient for preparation. Therefore, it was selected to prepare SEDDS formulation. The physicochemical properties of extract from Alisma orientalis by Supercritical CO2 extraction, such as the acid value, saponification value, peroxide value and emulsifying properties were determined. Then, the effects of storage time, temperature and the time of solar light irradiation on the physicochemical properties of the extract were also investigated. The optimum emulsification conditions of the extract is grinding for 3min at 25℃with a emulsifier which hydrophilic and lipophilic balance (HLB) value is from 15.2 to 15.6. The oxidation in the extract which could be accelerated by both temperature and solar light irradiation was continuously occurred during storage at room temperature and could lead to rancidification. The Saponification value increased along with the rising of storage time, temperature and the time of solar light irradiation and the solar light had stronger effect on saponification value.2 Screening and optimizing of SEDDS formulationSolubility experiment, self-emulsification test and the construction of pseudo-ternary phase diagram were used to screen appropriate excipients and the ratio of every ingredient. The final prescription was Cremophor RH40:isopropyl alcohol:Oil phase(GTCC:supercritical CO2 extract from Alisma orientalis= 3:1)= 0.42:0.28:0.30.3 The physicochemical properties and stability of the total terpenoids SEDDSThe total terpenoids SEDDS is a brownish yellow transparent fluid and it can form a transparent and lightly bluish O/W microemulsion with a droplet size of 28.1nm. The physicochemical properties of it were as follows:viscosity 18.7 mPa-s, refractive indices 1.4409, electrical conductivity 15.2μS/cm and emulsification time 133 s. The light stability and thermostability test and 6 monthes storage experiments shows that the appearance and effective ingredients of the total terpenoids SEDDS only has a small change during these experiments, indicating that the total terpenoids SEDDS has a good stability.4 In vitro release test of the total terpenoids SEDDSCompared with the alcohol solution of the supercritical CO2 extract from Alisma orientalis, the percentage release of drug form the total terpenoids SEDDS was higher and the release speed was faster in all the three release medias, namely distilled water, simulated gastric fluid and simulated intestinal fluid. In the three medias, the percentages release of the SEDDS were more than 60% at 5min, but the comparison formulation was less than 17%. |
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