ABSTRACT
Objective To establish an analytical method to investigate the protective effect of reversed lipid-based nanoparti-cle(RLBN)for topotecan(TPT)in artificial intestinal fluid. Methods Reversed lipid-based nanoparticle of TPT(RLBN-TPT)was prepared by the two-step methods of lyophilization and dissolution. An analytical method was established to determine the concentra-tions of both forms of TPT by high performance liquid chromatography(HPLC). Release curve of RLBN-TPT in simulated intestinal flu-id(SIF)was investigated to study the stability of TPT in gastrointestinal(GI)fluid. Results Both lactone and carboxylate forms of TPT were well separated and determined precisely by the optimized HPLC method. The calibration curves were linear within the range of 0.25-5μg/ml for both forms of TPT. Compared with free TPT,RLBN-TPT significantly improved the stability of TPT in SIF as the per-centage of carboxylate form was remarkably lower than the free TPT(P<0.05). Conclusion RLBN can significantly protect the TPT from hydrolysis in GI,which may lay the foundation for the deuelopment of oral chemotherapeutic drug with higher bioavailability.
ABSTRACT
Self-emulsifying drug delivery systems(SEDDS)are a vital tool in solving low oral bioavailability of poorly soluble drugs(PWSD). SEDDS may improve oral absorption via several mechanisms,however,enhancement of gastrointestinal solubilization of PWSD remains the most important factor of absorption enhancement. This review introduces the methods including dispersion tests and lipolysis tests in vitro as the indicators of potential performance in vivo. The use of these methods in vitro combined with oral bio?availability study is subsequently described,with particular focus on recent data which suggest that the digestion of lipid and surfac?tants present in SEDDS formulations impact on formulation performance in vivo. This review is expected to provide some guiding princi?ples on formulation design of SEDDS.
ABSTRACT
Objective To optimize and assess the formulation of self-microemulsifying drug delivery systems(SMEDDS)for artemether(ARM). Methods The optimized formulation of ARM-SMEDDS was screened by solubility,ternary phase diagram and cen?tral composite design-response surface methodology,with the particle size,Zeta potential and solubility as parameters. The physico-chemical property and dissolution characters of ARM-SMEDDS were also determined. Results The optimized SMEDDS was composed of Cremophor RH40(39.29%),Transcutol HP(35.71%)and MCT(25%). The average particle size after the emulsification was 24.52 nm,the Zeta potential was-10.10 mV,and the drug loading of self-microemulsifying exceeded 88 mg/g. Conclusion The opti?mized formulation of ARM-SMEDDS using the star point design-response surface methodology has significantly enhanced the solubility and in vitro dissolution of ARM.
ABSTRACT
Rheological properties of poloxamer 407 (brand named Pluronic F127) were examined by changing shear rate, temperature and the recovery properties of apparent viscosity after heating for several times. The results indicated that poloxamer 407 aqueous solution showed a Newtonian behavior at a low concentration while it might be a pseudoplastic fluid when the concentration reached a certain point. The thixotropy and the sol-gel transition temperature decreased with increasing the concentration (it could be an in situ gel at body temperature when the concentration of poloxamer 407 up to 15.25%). The results that obtained from the theological data would be useful in the application of poloxamer 407 such as in situ gel preparation.
ABSTRACT
The main purpose of this work is to prepare self-emulsifying drug delivery system (SEDDS) of a poorly water soluble drug, puerarin. Solubility of puerarin was determined in various oils and surfactants. Oleic acid and Tween 80 provided higher solubility. Addition of propylene glycol as cosurfactant improved solubility of puerarin and the spontaneity of self-emulsification. A series of mixtures comprising oleic acid, propylene glycol and Tween 80 were prepared and their self-emulsifying properties were studied. Pseudo-ternary phase diagrams were constructed to identify the efficient self-emulsification region and particle sizes of the resultant emulsions were determined using a laser diffraction sizer. The harmacokinetic behaviors of three different SEDDS formulations (F2, F3, F4) were investigated in Beagle dogs. The bioavailability was compared using the pharmacokinetic parameters, peak plasma concentration (Cmax), time to reach peak plasma concentration (Tmax) and total area under the plasma concentration-time curve (AUC0-t). AUC0-t was significantly higher in formulation F2 group (5.201±0.511) ng·mL-1·h and formulation F3 group (5.174±0.498) ng·mL-1·h than that in formulation F4 group (3.013±0.623) ng·mL-1·h. Also, Cmax was significantly higher in formulation F2 group (1.524±0.125) ng·mL-1 and formulation F3 group (1.513±0.157) ng·mL-1 than that in formulation F4 group (0.939±0.089) ng·mL-1. Further analysis of the data showed a statistically significant difference between F2 and F4 (P<0.01) as well as F3 and F4 (P<0.01) with regard to the values of AUC0-∞ and Cmax for three SEDDS formulations, but not between those of F2 and F3 (P>0.05). From these studies, the SEDDS formulation containing oleic acid (17.5%), Tween 80 (34.5%) and propylene glycol (34.5%) (w/w) was selected as an optimized SEDDS formulation of puerarin. The data suggest the potential use of SEDDS to improve oral absorption of puerarin.