A two-stage reverse dialysis in vitro dissolution testing method for passive targeted liposomes

Department of Pharmaceutical Sciences, University of Connecticut, 69 N Eagleville Rd U3092, Storrs, CT 06269, United States.
International Journal of Pharmaceutics (Impact Factor: 3.65). 04/2012; 426(1-2):211-8. DOI: 10.1016/j.ijpharm.2012.01.030
Source: PubMed


A novel two-stage reverse dialysis method has been developed for in vitro release testing of liposomal drug product with passive targeting characteristics. The first stage of the test is to mimic the circulation of liposomes in the body, whereas the second stage is to imitate the drug release process at the target. Buffer and surfactant solution were used during the first and second stages, respectively. For formulations containing high phase transition temperature lipids and high cholesterol content, no drug leakage was observed during the first stage of test. In the second stage, however, formulations with different compositions showed significant differences in terms of drug release rate, and discriminatory ability of the method was demonstrated. On comparing two different membrane diffusion techniques, dialysis and reverse dialysis methods, the reverse dialysis method showed significantly lower variation, and therefore is the preferred method. The developed in vitro release testing method should help to distinguish formulations with varied compositions for quality control testing purposes. This two-stage reverse dialysis method may pave the way to the development of more bio-relevant release testing methods for liposomal drug products.

Download full-text


Available from: Xiaoming Xu, Sep 29, 2015
175 Reads
  • Source
    • "Encapsulation efficiency (EE) of salidroside liposome was measured by dialysis method [12] [13] [14]. In brief, 2 mL of salidroside liposome was added into a dialysis bag with a hydrophilic cellulose membrane (3,000 MWCO) to remove free salidroside in PBS solution (200 mL, pH = 7.4). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to optimize the preparation conditions of salidroside liposome with high encapsulation efficiency (EE) and to study the immunological enhancement activity of salidroside liposome as porcine circovirus type 2 virus (PCV-2) vaccine adjuvant. Response surface methodology (RSM) was selected to optimize the conditions for the preparation of salidroside liposome using Design-Expert V8.0.6 software. Three kinds of salidroside liposome adjuvants were prepared to study their adjuvant activity. BALB/c mice were immunized with PCV-2 encapsulated in different kinds of salidroside liposome adjuvants. The PCV-2-specific IgG in immunized mice serum was determined with ELISA. The results showed that when the concentration of ammonium sulfate was 0.26 mol·L(-1), ethanol volume 6.5 mL, temperature 43°C, ethanol injection rate 3 mL·min(-1), and salidroside liposome could be prepared with high encapsulation efficiency of 94.527%. Salidroside liposome as adjuvant could rapidly induce the production of PCV-2-specific IgG and salidroside liposome I adjuvant proved to provide the best effect among the three kinds of salidroside liposome adjuvants.
    Evidence-based Complementary and Alternative Medicine 04/2015; 2015:178128. DOI:10.1155/2015/178128 · 1.88 Impact Factor
  • Source
    • "Recently, Xu et al. (2012) developed a novel two-stage reverse dialysis method for in vitro release testing of liposomal drug product. The first stage of the test is to mimic the circulation of liposomes in the body, whereas the second stage is to imitate the drug release process at the target. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The long-term controlled delivery of drugs has been successfully achieved by biodegradable polymeric particulate systems. The drug release testing method is important for the characterization of dosage form performance under in vitro standardized conditions and can provide insight into the in vivo performance of the drug product. In vitro drug release testing methods for polymeric particulate systems are classified into sample and separate (SS), dialysis, and continuous flow (CF) methods. In the SS method, the drug-loaded microparticles are suspended in a vessel and the samples for the analysis are obtained by separating the particles using filtration or centrifugation. The dialysis method physically separates microparticles from the release media by a membrane, which eliminates the undesired loss of particles during sample preparation and handling. The CF method uses apparatus consisted of flow-through cell that holds the sample, pump and water bath in closed or open ends system. In this method, the release media is continuously circulated through a cell containing drug-loaded microparticles. This review summarizes the principles of the drug release testing methods and discusses their characteristics with the recent research results.
    Journal of Pharmaceutical Investigation 08/2013; 43(4). DOI:10.1007/s40005-013-0072-5
  • Source
    • "The results confirm that dissolved drug molecules readily pass freely through the dialysis membrane. This may be because the molecular weight of the MX and RIF was much smaller than the pore sizes of membrane [4, 16]. Accordingly, MWCO of 12–14 kDa membranes were selected for all future release tests. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to assess the in vitro release kinetics of antituberculosis drug-loaded nanoparticles (NPs) using a "modified" cylindrical apparatus fitted with a regenerated cellulose membrane attached to a standard dissolution apparatus (modifiedcylinder method). The model drugs that were used were rifampicin (RIF) and moxifloxacin hydrochloride (MX). Gelatin and polybutyl cyanoacrylate (PBCA) NPs were evaluated as the nanocarriers, respectively. The dissolution and release kinetics of the drugs from loaded NPs were studied in different media using the modified cylinder method and dialysis bag technique was used as the control technique. The results showed that use of the modified cylinder method resulted in different release profiles associated with unique release mechanisms for the nanocarrier systems investigated. The modified cylinder method also permitted discrimination between forced and normal in vitro release of the model drugs from gelatin NPs in the presence or absence of enzymatic degradation. The use of dialysis bag technique resulted in an inability to differentiate between the mechanisms of drug release from the NPs in these cases. This approach offers an effective tool to investigate in vitro release of RIF and MX from NPs, which further indicate that this technique can be used for performance testing of nanosized carrier systems.
    07/2013; 2013(1):136590. DOI:10.1155/2013/136590
Show more