ABSTRACT
Objective To prepare dl-tetrahydropalmatine (dl-THP) ethosomes (ETS) and elucidate their transdermal absorption properties. Methods Dl-tetrahydropalmatine ethosomes (dl-THP ETS) were prepared by ethanol injection combined with pH-gradient active drug-loading method. Their physicochemical properties including elasticity, vesicle size, morphology and entrapment efficiency were characterized. Franz diffusion cells were used to investigate the ex vivo skin permeation characteristics of the formulation with liposomes (LPS) and tinctures being used as reference preparations. Results According to a preferred formulation of dl-THP ETS [dl-THP 100 mg, vitamin E 1.3 mg, soybean lecithin 1 200 mg, cholesterol 120 mg, absolute ethanol 9 mL and citrate buffered saline (pH 3.0) 21 mL, 0.1 mol/L NaOH solution suitable quantity (to adjust the pH value to 5.5) ], the obtained dl-THP ETS had an elasticity index of (20.1 ± 1.1) mL, an average size of (85.8 ± 0.9) nm with a polydispersity index of (0.082 ± 0.003) and an entrapment efficiency of (81.7 ± 3.2)%. The cumulative permeated drug quantity per unit area (Qn) of dl-THP ETS in 24 h was (2 306.4 ± 592.3) μg/cm2 with no significant difference compared with the Qn of the LPS [(2 434.2 ± 564.4) μg/cm2] (P > 0.05) and about 4 times of that of the tincture [(633.1 ± 218.0) μg/cm2] (P < 0.05). And the averages of RSD of the Qn at each time point were (28.37 ± 10.9)% and (62.83 ± 44.1)% for the ETS and LPS, respectively, indicating that the Qn fluctuation among samples of the ETS was smaller than that of the LPS (P < 0.05). Average correlation coefficients of (0.968 ± 0.033) and (0.882 ± 0.078) (P < 0.05) were obtained for the ETS and LPS respectively when their 24 h permeation curves were fitted to linear relationship, indicating the permeation of the former was closer to zero-order kinetics than that of the latter. Conclusion The dl-THP ETS have a high elasticity, a suitable size, a high entrapment efficiency, and enhanced and stable percutaneous absorption in line with zero-order kinetics.
ABSTRACT
Objective: To prepare sinomenine hydrochloride (SIN-HCl) liposomes with high entrapment efficiency (EE) and to illustrate the effects of drug quantity and particle size on EE. Methods: Centrifugation sedimentation-centrifugation ultrafiltration was employed to determine EE of liposomes. Thin film hydration (TFH), reverse phase evaporation (REV), and ether injection (EI) were screened based on EE and formability of liposomes. The effects of water type, pH value, ion concentration of hydration liquid, pH gradient active drug loading, lecithin-cholesterol ratio, and drug-lipid ratio on EE of liposomes were investigated. The relationship between EE and the factors affecting the drug quantity and particle size was probed with a comprehensive design experiment. The stability of typical liposomes was evaluated at 4 °C. Results: The optimal preparation technology was TFH for SIN-HCl liposomes and citrate buffer solution (CBS) was the best hydration liquid. The liposome EE increased with the increase of pH values of CBS. When the pH value of CBS was fixed, the EE increased as a result of decrease in the ion concentration of CBS. pH gradient active drug loading led to increase of EE. The preferable hydration liquid for liposomes was CBS with pH value of 2.5. The optimal ratio of soybean lecithin to cholesterol was 6:1. Increasing ratios of SIN-HCl to soybean lecithin from 1:6 to 6:6 led to a slight decrease in EE of liposomes without probe signification. A quantitative relationship was established between the EE and drug quantity and liposome size. The EE of SIN-HCl liposomes prepared by certain particle size and drug quantity could reach over 80%. The typical liposomes showed a good stability. Conclusion: The technology of pH gradient active drug loading is able to prepare SIN-HCl liposomes with high EE.