Résumé
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.
Résumé
Objective: To study the effect of ultrafine comminution on transdermal absorption and rheology of P. cuspidatum ointment (PCO). Methods: Common and ultrafine common powder of P. cuspidatum was got by common and ultrafine comminution technology respectively, and then prepared into common and ultrafine PCO. The skin permeation of common and ultrafine PCO was investigated through in vitro excised mice skin using improved Franz diffusion cell, with polydatin, resveratrol, and emodind as the indexes to compare the effect on the cumulative permeation amount and permeation rate of ointments. Then the effect on the rheology of ointments with apparent viscosity and yield stress as the indexes was compared. Results: The d0.9 of common and ultrafine powder of P. cuspidatum were (210.011 ± 3.468) and (63.496 ± 2.570) μm; And the spans were (5.412 ± 0.055) and (2.913 ± 0.117), respectively. The cumulative permeation amount of polydatin, resveratrol, and emodind of PCO were (2.100 3 ± 0.154 5), (2.114 5 ± 0.341 6), and (6.210 4 ± 0.750 0) μg/cm2, and the permeation rate were (0.175 3 ± 0.022 6), (0.234 0 ± 0.020 2), and (0.337 4 ± 0.051 6) μg/(cm2∙h), respectively. The ultrafine cumulative permeation amounts of polydatin, resveratrol, and emodind of PCO were (14.247 9 ± 4.875 0), (4.399 3 ± 0.628 7), and (6.768 6 ± 0.728 6) μg/cm2, which were 6.8, 2.1, and 1.1 times compared to common PCO; The permeation rates were (0.815 9 ± 0.277 1), (0.313 2 ± 0.043 0), and (0.393 7 ± 0.042 6) μg/(cm2∙h), which were 4.7, 1.3, and 1.2 times compared to common PCO respectively. The cumulative permeation amounts and permeation rates of ultrafine PCO were 6.8, 2.1, 1.1 and 4.7, 1.3, 1.2 times compared to common PCO. The apparent viscosity and yield stress of common and ultrafine PCO were 34.940, 8.865 Pa∙s and 41.211, 7.381 Pa. Conclusion: Compared with common PCO, the transdermal permeability and fineness of ultrafine PCO were improved, and the apparent viscosity and yield stress decreased, which facilitates of spreadability.
Résumé
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.