The development of self-nanoemulsifying drug delivery systems(SNEDDS) to enhance the oral bioavailability of lipophilic drugs is usually based on traditional one-factor-at-a-time approaches. These approaches may be in...The development of self-nanoemulsifying drug delivery systems(SNEDDS) to enhance the oral bioavailability of lipophilic drugs is usually based on traditional one-factor-at-a-time approaches. These approaches may be inadequate to analyse the effect of each excipient and their potential interactions on the emulsion droplet size formed when dispersing the SNEDDS in an aqueous environment. The current study investigates the emulsion droplet sizes formed from SNEDDS containing different levels of the natural surfactant monoacyl phosphatidylcholine to reduce the concentration of the synthetic surfactant polyoxyl 40 hydrogenated castor oil(Kolliphor ~? RH40). Monoacyl phosphatidylcholine was used in the form of Lipoid S LPC 80(LPC, containing approximately 80% monoacyl phosphatidylcholine, 13% phosphatidylcholine and 4% concomitant components). The investigated SNEDDS comprised of long-chain or medium-chain glycerides(40% to 75%), Kolliphor ~? RH40(5% to 55%), LPC(0 to 40%) and ethanol(0 to 10%). D-optimal design, multiple linear regression, and partial least square regression were used to screen different SNEDDS within the investigated excipient ranges and to analyse the effect of each excipient on the resulting droplet size of the dispersed SNEDDS measured by dynamic light scattering. All investigated formulations formed nano-emulsions with droplet sizes from about 20 to 200 nm. The use of mediumchain glycerides was more likely to result in smaller and more monodisperse droplet sizes compared to the use of long-chain glycerides. Kolliphor~? RH40 exhibited the most significant effect on reducing the emulsion droplet sizes. Increasing LPC concentration increased the emulsion droplet sizes, possibly because of the reduction of Kolliphor~? RH40 concentration. A higher concentration of ethanol resulted in an insignificant reduction of the emulsion droplet size. The study provides different ternary diagrams of SNEDDS containing LPC and Kolliphor ~? RH40 as a reference for formulation developers.展开更多
The surface properties of monoacyl trehaloses with different acyl chains were investigated at 30℃,40℃,50℃,and 60℃.Monoacyl trehaloses were enzymatically synthesized and purified with silica gel column chromatograp...The surface properties of monoacyl trehaloses with different acyl chains were investigated at 30℃,40℃,50℃,and 60℃.Monoacyl trehaloses were enzymatically synthesized and purified with silica gel column chromatography and semi-preparative high-performance liquid chromatography(HPLC),and the purity of products was identified by mass spectrometry(MS)and nuclear magnetic resonance(NMR).The surface tension of monoacyl trehalose in pure water was measured using Doüy ring method at different temperatures.The critical micelle concentrations(CMC),surface tension at the CMC,γCMC,and residual area per molecule,a,were estimated from the curves.The CMC value of unsaturated monoacyl trehalose was affected by both the degree of unsaturation and the acyl chain length,and the effect of chain length on the CMC value was much stronger than that of the unsaturation degree.However,there was no significant dependency of theγCMC value and a values on the chain length or the unsaturated degree.展开更多
基金Financial support from the University of Copenhagen and the Phospholipid Research Center(Heidelberg,Germany)is kindly acknowledged
文摘The development of self-nanoemulsifying drug delivery systems(SNEDDS) to enhance the oral bioavailability of lipophilic drugs is usually based on traditional one-factor-at-a-time approaches. These approaches may be inadequate to analyse the effect of each excipient and their potential interactions on the emulsion droplet size formed when dispersing the SNEDDS in an aqueous environment. The current study investigates the emulsion droplet sizes formed from SNEDDS containing different levels of the natural surfactant monoacyl phosphatidylcholine to reduce the concentration of the synthetic surfactant polyoxyl 40 hydrogenated castor oil(Kolliphor ~? RH40). Monoacyl phosphatidylcholine was used in the form of Lipoid S LPC 80(LPC, containing approximately 80% monoacyl phosphatidylcholine, 13% phosphatidylcholine and 4% concomitant components). The investigated SNEDDS comprised of long-chain or medium-chain glycerides(40% to 75%), Kolliphor ~? RH40(5% to 55%), LPC(0 to 40%) and ethanol(0 to 10%). D-optimal design, multiple linear regression, and partial least square regression were used to screen different SNEDDS within the investigated excipient ranges and to analyse the effect of each excipient on the resulting droplet size of the dispersed SNEDDS measured by dynamic light scattering. All investigated formulations formed nano-emulsions with droplet sizes from about 20 to 200 nm. The use of mediumchain glycerides was more likely to result in smaller and more monodisperse droplet sizes compared to the use of long-chain glycerides. Kolliphor~? RH40 exhibited the most significant effect on reducing the emulsion droplet sizes. Increasing LPC concentration increased the emulsion droplet sizes, possibly because of the reduction of Kolliphor~? RH40 concentration. A higher concentration of ethanol resulted in an insignificant reduction of the emulsion droplet size. The study provides different ternary diagrams of SNEDDS containing LPC and Kolliphor ~? RH40 as a reference for formulation developers.
基金supported,in part,by the National Natural Science Foundation of China(Grants No.20401007)the Ministry of Education,China(Grants No.NCET-07-0377 and No.IRT0627).
文摘The surface properties of monoacyl trehaloses with different acyl chains were investigated at 30℃,40℃,50℃,and 60℃.Monoacyl trehaloses were enzymatically synthesized and purified with silica gel column chromatography and semi-preparative high-performance liquid chromatography(HPLC),and the purity of products was identified by mass spectrometry(MS)and nuclear magnetic resonance(NMR).The surface tension of monoacyl trehalose in pure water was measured using Doüy ring method at different temperatures.The critical micelle concentrations(CMC),surface tension at the CMC,γCMC,and residual area per molecule,a,were estimated from the curves.The CMC value of unsaturated monoacyl trehalose was affected by both the degree of unsaturation and the acyl chain length,and the effect of chain length on the CMC value was much stronger than that of the unsaturation degree.However,there was no significant dependency of theγCMC value and a values on the chain length or the unsaturated degree.
