Study of the preparation of sustained-release microspheres containing zedoary turmeric oil by the emulsion-solvent-diffusion method and evaluation of the self-emulsification and bioavailability of the oil.

The purpose of this study was to design a sustained-release formulation of an oily drug. The sustained-release microspheres with self-emulsifying capability containing zedoary turmeric oil (ZTO) were prepared by the quasi-emulsion-solvent-diffusion method. The micromeritic properties, the efficiency of emulsification and the drug-release behavior of the resultant microspheres were investigated. The bioavailability of the microspheres was compared with conventional ZTO self-emulsifying formulations for oral administration using 12 healthy rabbits. An HPLC method was employed to determine the concentration of germacrone in plasma, which was used as an index of ZTO. Spherical and compacted microspheres with average diameters of 100-600 microm have been prepared, and their release behavior in distilled water containing 1.2% (w/v) of polysorbate-80 can be controlled by the ratio of polymer/Areosil200 in the microspheres. The resultant emulsions with mean droplet sizes of 200-500 nm are produced when the microspheres are immersed in phosphate buffer (pH 6.8) under gentle agitation. The stability and the droplet size of the resultant emulsions are also affected by the polymer/Areosil200 ratio in the formulation, while the amount of talc has a marked effect on the self-emulsifying rate. The plasma concentration-time profiles with improved sustained-release characteristics were achieved after oral administration of the microspheres with a bioavailability of 135.6% with respect to the conventional self-emulsifying formulation (a good strategy for improving the bioavailability of an oily drug). In conclusion, the sustained-release microspheres with self-emulsifying capability containing ZTO have an improved oral bioavailability. Our study offers an alternative method for designing sustained-release preparations of oily drugs.

A HPLC method for the analysis of germacrone in rabbit plasma and its application to a pharmacokinetic study of germacrone after administration of zedoary turmeric oil.

A validated new, simple and highly sensitive reversed-phase HPLC method is developed for studying the pharmacokinetics of germacrone after intravenous administration of zedoary turmeric oil (ZTO) oil-in-water microemulsion. The method did not require a complex and expensive equipment. A high extraction recovery (>80%) of germacrone was obtained. Linear calibration curves obtained with the peak-area ratio (y) of germacrone to internal standard (tanshinoneIIA) versus drug concentration (x) were found to be linear between 8.08 and 808 ng/ml. The limit of quantitation was 8.08 ng/ml. The monitored compounds were completely separated from others in ZTO and from endogenous species in plasma by HPLC. Pharmacokinetic investigations were performed on 18 male rabbits after intravenous administration of ZTO microemulsion via the ear vein at germacrone doses of 3.2, 6.4 and 9.6 mg/kg. The plasma concentration-time data fit to a two-compartment intravenous model with a weight of 1/C(2) (C: germacrone concentration in plasma). Germacrone exhibited linear pharmacokinetics after intravenous administration of ZTO microemulsion to rabbits over the germacrone dose range 3.2-9.6 mg/ml.

A novel formulation design about water-insoluble oily drug: preparation of zedoary turmeric oil microspheres with self-emulsifying ability and evaluation in rabbits.

To enhance in vivo absorption of zedoary turmeric oil (ZTO) and develop new formulations of a water-insoluble oily drug, novel ZTO microspheres with self-emulsifying ability, called self-emulsifying microspheres here, were prepared in a liquid system by the quasi-emulsion solvent diffusion method. The microspheres containing hydroxypropyl methylcellulose acetate succinate (HPMCAS-LG), Talc and Aerosil 200 formed the stable surfactant-free emulsion when exposed to the pH 6.8 phosphate buffer, and were significantly different from the conventional self-emulsifying systems (SES), defined as isotropic mixtures of oil, surfactant and drug. Micromeritic properties, the efficiency of emulsification and the drug-release rate of the resultant microspheres were investigated. The bioavailability of the microspheres to the conventional self-emulsifying formulation for oral administration was evaluated in 12 healthy rabbits. A HPLC method was employed to determine the plasma concentration of Germacrone, an indexical component found in ZTO. The release rates of ZTO and Germacrone from the microspheres were enhanced significantly with increasing amounts of dispersing agents, and the efficiency of self-emulsification greatly depended on the HPMCAS-LG/Aerosil 200 ratio. The emulsion droplets released from the microspheres were much smaller than that of the conventional SES. The microsphere bioavailability (F) to the conventional SES for oral administration was 157.7%. Our method greatly improved the bioavailability of the water-insoluble oily drug from the self-emulsifying microspheres over the conventional SES and it is useful for the oily drug to form solid preparations.

[Absorption of zedoary oil in rat intestine using in situ single pass perfusion model].

AIM: To study the absorption of zedoary oil in intestine of rat. METHODS: In situ single pass perfusion model was used and the concentrations of three components in perfusate were determined by HPLC in combination with diode array detection. RESULTS: The P(app) s of curcumol, curdione and germacrone were all low and had no significant difference (P > 0.05) at zedoary oil concentration of 0.4, 0.8 and 1.2 mg x mL(-1) in transmucosal fluid or in four different regions of intestine of rat [duodenum, jejunum, ileum, colon]. The absorption rates of germacrone and curdione were faster than curcumol's in this study. CONCLUSION: The zedoary oil concentration in transmucosal fluid had no significant effect on the P(app) s within the scope of 0.4-1.2 mg x mL(-1). The absorption of curcumol, curdione and germacrone showed the passive diffusion process, and didn't contain a special absorption window.