Determination of Equilibrium Solubility and Apparent Oil/water Partition Coefficients of Rhein / 医药导报

Objective To determine the solubility of rhein in different vehicles and its partition coefficients in the n-octanol-water system for designing new formulations. Methods High performance liquid chromatography(HPLC) method was established to determine the concentration of rhein in water,different pH solutions and different solvents;the partition coefficients for the n-octanol- buffer solution systems were determined by shaking flask method. Results The equilibrium solubility of Rhein was 3.89 μg·mL-1and the lgP was 2.79 in water at 37 ℃.The solubility of rhein was increased with the raise of pH, which could reach 362.20 and 431.65 μg·mL-1in phosphate buffer solution at pH 6.8 and 7.4,respectively.Solubility of rhein in the semi polar solvent was relatively good,which can up to 2 971.74 μg·mL-1in PEG400.The oil-water partition coefficients of rhein were decreased with the increase of pH,and were 0.83 and 0.54 in phosphate buffer solution at pH 6.8 and 7.4,respectively. Conclusion Rhein is almost not soluble in water.With the raise of pH,the solubility is increased but the oil-water partition coefficient is decreased.

Optimization of multicomponent microemulsion of Chinese materia medica with different oil-water partition coefficients by simplex lattice method / 中草药

Objective To prepare multicomponent microemulsion of Chinese materia medica (CMM) with different oil-water partition coefficients (logP values) by simplex lattice method and evaluate its quality. Methods The surfactants, cosurfactants and oil phases were screened by saturated solubility method. Ochratins, ligustrazine, ferulic acid, puerarin and geniposide were model drugs to represent the complex components of CMM. Based on the pseudo-ternary diagram, simplex lattice method was adopted to optimize the multicomponent microemulsion of CMM with different logP values by appearance, particle size and polydispersity index as evaluation indexes. The experimental design and model building were constructed by Design Expert 8.06 software to optimize the response surface data analysis and validate the optimal prescription composition. The quality of microemulsion was evaluated by observing appearance and stability as well as measuring particle size and potential. Results The optimum formulation was oleic acid-Labrasol-propylene glycol-water (5.303:29.336:7.334:58.027). The prepared microemulsion was clear in appearance with good yellowish color and stable property. The average particle size was (118.77 ± 0.37) nm, PDI was 0.282 ± 0.02 and Zeta potential was (0.346 ± 0.05) mV. Conclusion The results indicated that the multicomponent microemulsion of CMM with different logP values is optimized and the drug loading was high. The multicomponents microemulsion of CMM with different logP values (-1.01-3.85) is established and optimized, providing a feasible microemulsion carrier for the multicomponent CMM to simplify its prescription screening work.

Equilibrium solubilities, oil-water partition coefficients and in vitro skin permeation features of two constituents in total alkaloids from Strychni Semen / 中成药

AIM To investigate the equilibrium solubilities,oil-water partition coefficients and in vitro skin permeation features of brucine and strychnine in total alkaloids from Strychni Semen.METHODS Saturated dissolution method was applied to determining the equilibrium solubilities of two constituents in ethanol (10％,20％,30％,60％,90％,anhydrous ethanol),trichloromethane,n-octanol and surfactants (0.5％ tween,0.5％ sodium deoxycholate,0.5％ oleic acid).Shake-flask method was adopted in detecting their oil-water partition coefficients in PBS (pH 2.5,4.0,5.0,5.8,6.8,7.0,7.4,9.0).Modified Franz diffusion cell method was used for evaluating their in vitro skin permeation features in PBS,20％ ethanol and anhydrous ethanol.RESULTS Both brucine and strychnine showed the highest equilibrium solubilities in trichloromethane and the lowest equilibrium solubilities in surfactants.The equilibrium solubility of strychnine was higher than that of brucine in ethanol (＞ 20％) or PBS (pH ＜ 8.0),which reached the highest in 60％ ethanol and pH 2.5 PBS,respectively.The similar oil-water partition coefficients of two constituents,proportional to pH value,reached the highest at pH9.0.And they exhibited the highest accumulated transdermal absorptivities in anhydrous ethanol and pH 9.0 PBS,respectively.CONCLUSION Solvent type has obvious effects on the equilibrium solubilities,oil-water partition coefficients and in vitro skin permeation features of both brucine and strychnine.This study can provide a reference for the bioavailability improvement of transdermal drug delivery and development of related preparations.

Equilibrium solubilities, oil-water partition coefficients and in vitro skin permeation features of two constituents in total alkaloids from Strychni Semen / 中成药

AIM To investigate the equilibrium solubilities,oil-water partition coefficients and in vitro skin permeation features of brucine and strychnine in total alkaloids from Strychni Semen.METHODS Saturated dissolution method was applied to determining the equilibrium solubilities of two constituents in ethanol (10％,20％,30％,60％,90％,anhydrous ethanol),trichloromethane,n-octanol and surfactants (0.5％ tween,0.5％ sodium deoxycholate,0.5％ oleic acid).Shake-flask method was adopted in detecting their oil-water partition coefficients in PBS (pH 2.5,4.0,5.0,5.8,6.8,7.0,7.4,9.0).Modified Franz diffusion cell method was used for evaluating their in vitro skin permeation features in PBS,20％ ethanol and anhydrous ethanol.RESULTS Both brucine and strychnine showed the highest equilibrium solubilities in trichloromethane and the lowest equilibrium solubilities in surfactants.The equilibrium solubility of strychnine was higher than that of brucine in ethanol (＞ 20％) or PBS (pH ＜ 8.0),which reached the highest in 60％ ethanol and pH 2.5 PBS,respectively.The similar oil-water partition coefficients of two constituents,proportional to pH value,reached the highest at pH9.0.And they exhibited the highest accumulated transdermal absorptivities in anhydrous ethanol and pH 9.0 PBS,respectively.CONCLUSION Solvent type has obvious effects on the equilibrium solubilities,oil-water partition coefficients and in vitro skin permeation features of both brucine and strychnine.This study can provide a reference for the bioavailability improvement of transdermal drug delivery and development of related preparations.

Transdermal enhancement effect and mechanism of iontophoresis for non-steroidal anti-inflammatory drugs.

Iontophoresis is an important approach to improve transdermal drug delivery. However, The transdermal enhancement mechanism of iontophoresis was not well known. The relationship between the physicochemical properties of drugs and the transdermal enhancement effect of iontophoresis was revealed in this study. Non-steroidal anti-inflammatory drugs (NSAIDs) were used as the models, including aspirin, ibuprofen and indomethacin. Their oil-water partition coefficients were measured. The carbomer-based hydrogels of them were prepared. Iontophoresis significantly enhanced in vitro transdermal delivery across the rat skins. Strong lipophilicity could lead to high permeation of drugs. However, the dissociation extent (indicated as pKa) of drugs was the key factor to determine the transdermal enhancement effect of iontophoresis. The more dissociation the drugs were, the higher the transdermal enhancement effect of iontophoresis. The drug-loaded hydrogels combined with iontophoresis improved the treatment of rat raw's inflammatory syndrome. Iontophoresis significantly improved the drugs penetrating into the hypodermis, dermis and epidermis, more deeply than the application of drugs alone according to the experimental result of 5-carboxylfluorescein hydrogels. Iontophoresis led to the unordered arrangement of skin intercellular lipids, the significantly increased flowability and loose stratum corneum structure. Iontophoresis is a promising approach to improve transdermal drug delivery with safety and high efficiency.

Determination of Oil-water Partition Coefficients of Rosiglitazone / 中国药房

OBJECTIVE:To determine the oil-water partition coefficients (logP) of rosiglitazone at different pH values by two kinds of methods.METHODS:A shake flask-ultraviolet spectrophotometry method was used to determine plasma concentration of rosiglitazone in water phase and organic phase at variable pH values (0.95,2.0,3.0,4.0,5.07,5.7,6.55,7.06,7.5,8.15,9.21) to calculate logP by using with n-caprylic alcohol-water as simulation system.Above logP values were compared with that calculated by Pallas software.RESULTS:The logP value was lower than 1 when pH value was lower than 4;the logP value was higher than 1 when pH value was ranged from 5 to 9.Measured logP values were in good agreement with that calculated by Pallas software.CONCLUSION:Rosiglitazone exists in the form of hydrochloride salt with good water solubility (pH