ABSTRACT
@#Liposome, a new dosage form, has become important in improving in vivo behavior of drugs or realizing targeted drug delivery. Study and control of its critical processes and quality attributes are the main challenges in the current research on liposomes. The degree of encapsulation can determine drug''s effect in vivo directly, thus entrapment efficiency (EE) has turned into one of the critical quality attributes of liposome.In this paper some methods commonly used for the determination of EE and their characteristics are summarized and analyzed, and the main factors to be considered for the determination are discussed.
ABSTRACT
Objective: To study the preparation process of ligustrazine microemulsion delivery system and evaluate its physical pharmacy properties; Microemulsions of different particle sizes were prepared in different oil phases, and the effect of particle size factors on the release behavior of the preparation was investigated. Methods: Taking the solubility of ligustrazine as index, the oil phase, emulsifier, and co-emulsifier were screened. The microemulsion formulation was optimized by pseudo-ternary phase diagram method. The encapsulation efficiency and drug loading was studied by ultrafiltration centrifugation. The particle size and potential were detected by the particle size analyzer. The release behavior of microemulsions with different particle sizes was compared by dialysis bag method. Results: The tetramethylpyrazine microemulsion was successfully prepared, and the appearance was clear and transparent. The average pH value was about 5.46. The detection method of microemulsion encapsulation rate was successfully established. When the drug loading of ligustrazine was 1.2 mg/mL, the encapsulation efficiency was (87.43 ± 0.20)%. The microemulsions of different particle sizes were prepared by changing the oil phase (ethyl oleate, oleic acid, and IPM). When the drug loading was 1.2 mg/mL, the three particle sizes were (16.80 ± 0.91), (129.50 ± 1.21), and (18.51 ± 0.24) nm, respectively. The release test showed that the release rate of all three could reach more than 90% within 4 h, and there was no significant difference. Conclusion: The uniform and stable tetramethylpyrazine microemulsion is successfully prepared; The release behavior of different tetramethylpyrazine microemulsions is not affected by the particle size factor.
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.
ABSTRACT
Objective: To develop a method for determining the entrapment efficiency of sinomenine hydrochloride (SM-HCl) liposomes and to illuminate the drug retention property in the liposomes. Methods: Thin film hydration method was employed to prepare SM-HCl liposomes. HPLC was used to determine drug content of the liposomes. A Kromasil ODS C18 column (250 mm x 4.6 mm, 5 μ) was used with an isocratic elution composed of methanol, water, and ethylenediamine in the ratio of 55 : 45 : 0.225 at a flow rate of 1.0 mL/min. The column was maintained at 30 °C. The UV detector was set at 265 nm. Centrifugation sedimentation combined with centrifugation ultrafiltration was used to determine drug entrapment efficiency of the liposomes. The entrapment efficiencies of an SM-HCl liposome sample (hydrated with citric buffer solution at pH 7.0) and its diluted sample were compared. Results: The pharmaceutical excipients and solvents for analysis had no interference with the determination of sinomenine. Sinomenine had a good linear relation in the range of 9.82-78.6 μg/mL (r = 0.999 7), the intra-day and inter-day precisions were with RSD≤2.1% and the averaged recovery was within 99.29%-100.8%. SM-HCl solution (50 μL) was able to saturate the drug absorption of ultrafiltration films. The entrapment efficiencies of the SM-HCl liposome sample (hydrated with citric buffer solution at pH 7.0) and its double-volume diluted sample were 33.16% and 14.75%, respectively. Conclusion: HPLC and centrifugation sedimentation combined with centrifugation ultrafiltration are able to determine the entrapment efficiency of SM-HCl liposomes efficiently and accurately. Initial filtrate (50 μL) should be discarded in the process of ultrafiltration in order that the drug concentration in filtrate may be equal to that of external aqueous phase of liposomes. The retention of sinominine in the liposomes is poor, although it has considerable affinity to the lipid bilayers.