Study On The Preparation Of Zedoary Turmeric Oil Dry Emulsion And Lipid Pellets And In Vivo Evaluation

Solidification of oily drugs has been attracted wide attention of the pharmaceutics researchers in recent years. One of the main goals in pharmaceutical technological field was to obtain the solid preparation which has fast release rate and high bioavailability as liquid emulsion. In this study, a fast release dry emulsion was prepared by grinding and drying method, zedoary turmeric oil (ZTO), which has strong pharmacological action including suppression of tumors and anti-bacterial effect, was used as model drug, and polymer was applied as the emulsifier and carrier. ZTO enteric soluble dry emulsion (ZTO ESE) was obtained with the same method as preparing the fast release dry emulsions, using Aerosil 200 as emulsifier and enteric soluble polymer as carrier. ZTO lipid pellets were prepared using melting and cooling method with the help of lipid material ATO 888. The mechanism of polymer and small solid particles stabilizing the emulsion was investigated and discussed. Finally, the bioavailabilities of ZTO after oral administration of fast release dry emulsion, ZTO ESE and ZTO lipid pellets were evaluated in rabbits using ZTO self emulsifying emulsion as reference.A novel and simple method, grinding and drying method, was developed to prepare the dry emulsion using Eudragit E100 as emulsifier and carrier. First, Eudragit E100 was dissolved in the phosphoric acid solution as water phase, and then the oil phase was added gradually to the water phase under continuous grinding until a viscous semi-solid emulsion was achieved. The resultant semi-solid emulsion was spread on a flat glass plate with a thickness of about 0.5mm, followed by drying in a oven, the temperature of which was maintained at 40±1℃for about 4 h to get a transparent dry film. After the dry film was cooled down to room temperature, it was triturated to powders of suitable particle size. Formulation factors and procedure factors affecting the dissolution properties of ZTO fast release emulsions were investigated, and optimal formula was achieved. Residue efficiency of ZTO and three indexical components in ZTO fast release dry emulsion was over 85%. The cumulative release of ZTO in ZTO fast release dry emulsion was over 75% at 5min and over 85% at 15min in pH1.2 HCL solution. The same method was employed in the preparation of ZTO enteric soluble emulsion using Aerosil 200 as emulsifier and Eudragit L 100-55 as enteric soluble carrier. The cumulative release of ZTO in ZTO ESE was less than 10% in the pH1.2 HCL solution at 2h, and subsequently, rapid release rate was obtained in the pH6.8 phosphate buffer. ZTO lipid pellets were prepared by melting ATO 888 and ZTO together and cooled in ice water.Stability of ZTO fast release dry emulsion, ZTO ESE and ZTO lipid pellets were studied. It was found that the three preparations were stable under cool environment (4-8℃), and ZTO lipid pellets were stable under room temperature (25℃, RH 60%). ZTO fast release drying emulsion and ZTO ESE were not stable under room temperature (25℃, RH 60%) and accelerating environment (40℃, RH 75%).The mechanism of polymer and solid particles stabilizing the emulsion was also investigated. It was shown that a good polymer stabilizer for the emulsion requires, firstly, suitable hydrophilic group and hydrophobic group, and, secondly, simple main chain structure, so that the hydrophilic group of polymer can easily diffuse and absorb on the surface of the oil drop. Experimental results also indicated that solid particles which have suitable hydrophilic and hydrophobic property could stabilize the emulsion. The hydrophilic solid particles, which have a larger oil-solid contact angle, have better ability of stabilizing the emulsion.The bioavailability studies were carded out in rabbits after oral administration of ZTO fast release emulsion, ZTO ESE and ZTO lipid pellets using ZTO SES as reference. The relative bioavailability of the above three preparations was 92.79%, 82.56% and 66.18%, respectively.Some investigations, which have not reported at present, have been carded out in this work, such as using Eudragit E100 as polymer emulsifier, preparing ZTO fast release dry emulsion applying polymer as emulsifier and carder, preparing ZTO enteric soluble dry emulsion using Aerosil 200 as emulsifier and enteric soluble polymer as enteric carrier, preparing ZTO lipid pellets using ATO 888 as lipid carrier.