Preparation And Quality Control Of Matrine Ethosome Thermosensitive Gels

Matrine is an alkaloid of tetracyclic quinolizidines, extracted from Chineseherbal medicine, Sophora Flavescens Ait, S.Qlopecuroioles L, S.SnbprostratachunatT.Chon. The studies of pharmacological have shown that Matrine has anti-bacterial,anti-inflammatory, insecticidal activity; which is effective for the treatment of variousinflammatory gynecological diseases. Ethosomes are soft vesicles made ofphospholipids, alcohol (in high concentration) and water, which are new liposomeswith high deformability, entrapment efficiency, and deliver drugs through the stratumcorneum barrier into the deep layer of skin or blood circulation.Thus they areespecially suitable for the carrier of external administration and cutaneouspenetration.Thermosensitive in situ gel is an intelligent gel, which is in response totemperature changes. And it’s in a flowable gel solution, then it can be filled into thegaps between tissues and cavum after injection.The phase transition occurs in a shorttime, for the body temperature is higher than its phase transition temperature, it formsa high viscosity、difficult flowable semi-solid gel at the site of injection, which canfacilitate local adminstration or prolong the residence time of drug at theadministration site to maximize the efficacy.The aim of this research was to prepare matrine ethosome thermosensitive gels,to utilize the compound carriers of ethosomes and thermosensitive gels, which canprolong the action time of matrine and the improve the treatment effect. Furthermore,we should ensure the formulation with controllable quality ang stable performance,then to establish the foundation for further study of the formulation.The high-performance liquid chromatography (HPLC) method was establishedto determine the matrine concentration of matrine ethosomes and matrine ethosomethermosensitive gels.Matrine ethosomes was prepared by alcohol injection method.The bestpreparation formulation and technology of matrine ethosomes was optimized byorthogonal experiment with the entrapment efficiency as indicator. The bestprescription was: The mass ratio of drug to lipids was1:2, the volume proportion ofethanol and propylene glycol to phosphate buffer was4:6, and the volume ratio of ethanol to propylene glycol was7:3. The stirring rate was900rpm, the brooding timewas30min, and the water-bath temperature was (37±1)℃. The average entrapmentefficiency of the optimal formulation was66.98%. The morphology of the preparedmatrine ethosomes were observed by Transmission Electron Microscopy (TEM),which were spherical vesicles in shape. The Particle size and size distribution of theprepared matrine ethosomes were determined by dynamic light scattering (DLS)method, and particle size distribution was from271to280nm and the averagediameter was275.8nm with a narrow size distribution. The results of the preliminarystability experiment showed that the matrine ethosomes should be stored at thetemperature of4-8℃, and keep away from air and light.The preformulation studies were performed to investigate the thermosensitiveproperties of poloxamer407and the effects of adjuvant material on gelationtemperature of poloxamer407. The best preparation formulation and technology ofthe matrine ethosome thermosensitive gels was optimized by orthogonal experimentwith the gelation temperature as indicator. The optimum formulations were: chitosansolution (final concentration0.08%), glycerol7.5%, poloxamer40718%, poloxamer1883%, acetic acid-sodium acetate buffer solution (pH4.5), and matrine ethosomesolution3.5g. The gelation temperature of the formulation was28.3±0.2℃; in vitrorelease experiments showed that the behavior of matrine from the formulationsfollowed the Zero Order kinetics model.The matrine ethosome thermosensitive gels were prepared by the optimalformulation, and to evaluate its quality and preliminary stability.The formulation waswhey colored-translucent gel under the srorage conditions solution, and then ittranslated to a semi-solid gel when the gelation temperature was reached. Thepreliminary stability studies showed that the formulation should be stored at a lowtemperature (4-8℃), protected from light.The results show that the matrine ethosome thermosensitive gels were qualitycontrol with simple preparation technology, high safety and stability, which may bepromising to develop as a new vaginal adminstration formulation for treatinggynecological diseases.