Study On Berberine Hydrochloride Self-emulsifying Microsphere By Membrane Emulsification Technology

Self-emulsifying drug delivery systems (SEDDS) is composed of oil phase, surfactant and co-surfactant, which are thermodynamically stable and homogeneous mixture. It can mold of emulsion with the particle size less than1000nm in slight shock in vitro or intestine movement in vivo. SEDDS is normally liquid at room temperature, leading to some problems such as hard of carrying, high production cost, drug or excipients lixiviation in storage and drug chemical stability. To overcome the shortcomings of SEDDS, more attention has been paid to solid self-emulsifying drug delivery system(S-SEDDS).Microsphere is a spherical entity with the particle size between1to40μm which is formed by dissolving or dispersing the drug in some polymer material matrix. It has many advantages for oral administration, to be more specific, the stability of drug was improved, disagreeable taste was concealed, drug release rate was controlled. In addition, after changing liquid drug to solid, make it easy for applications and storage.In order to integrate the advantages of SEDDS and microspheres, solubility test and pseudo-ternary phase diagram were employed to select the optimal prescription of liquid SEDDS. Berberine hydrochloride self-emulsifying microsphere (BH-SEM) was prepared by membrane emulsification technology and ionic gelatinous method.The main works of research was as follows:(1) This experiment established an analytical method of high performance liquid chromatography (HPLC), the good linear range of250～8000n-gmL-1, the mean recovery of96.1%and quantitative detection limit of40n·gmL-1.The accuracies of within-day and between-day were less than1%. The stability was favorable at-20℃and37℃.(2) The optimum mass ratio of4:1was selected for surfactant and co-surfactant by pseudo-ternary phase diagram. The optimal prescription of liquid SEDDS were Capmul MCM:Cremophor EH40:Labrsaol:1-2propanediol=20:32:32:16.It was selected by solubility measurement results and the principle that is the proportion of surfactant prescription should not be too high.(3) The BH-SEM was prepared using membrane emulsification technology and ionic gelatinous method with the solid carrier in a gel formed by sodium alginate and calcium chloride with the optimum mass ratio of4:1of SEDDS. Influence of different excipients was sudied using encapsulation as standard. The results showed that the encapsulation efficiency was increased gradually with increasing self-emulsifying component and calcium chloride concentration, but the encapsulation efficiency was increased first and then decreased with increasing the content of sodium alginate concentration. In vitro characterization of BH-SEM showed that the solid self-emulsifying microsphere had average diameter of10.92nm, encapsulation efficiency of32.57%and the droplet size of reconstituted micro-emulsion of156.5nm. Berberine hydrochloride was dispersed in microsphere in non-crystalline form.In vitro release of the self-emulsifying microsphere showed pH response characteristic.Our project reported preparing the self-emulsifying microsphere by membrane emulsification technology at first time. Microsphere was loaded hydrophobic drugs, compared with the other ways of preparation methods, this method showed many advantages including reducing the residues of organic solvents in the formulation and increasing the dissolution of insoluble drugs.In order to compare the bioavailability of BH-SEM with commercially tablets and BH, we should investigate Pharmacokinetics later. However, in order to improve the encapsulation efficiency in the further, it is necessary to explore the impact of the different prescription process encapsulation efficiency.