Article

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: 3.99). 04/2012; 426(1-2):211-8. DOI: 10.1016/j.ijpharm.2012.01.030
Source: PubMed

ABSTRACT 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.

0 Bookmarks
 · 
244 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A novel method was developed and optimized to measure the in vitro release (IVR) of two liposomal ciprofloxacin formulations under development to treat lung infection. The release agent, bovine serum, has components that interact with liposomes to cause the encapsulated drug to be released. The precision and accuracy of the method were characterized. The method has a nearly linear release phase initially, which then approaches a plateau value after 2–4 h. The robustness of the method was verified over a range of release agent and liposomal concentrations, and in response to changes in incubation temperature, buffer pH, and storage containers of serum. For this “sample and separate” IVR method, there is less than 2% release at the T = 0 time point, indicating negligible artifactual release before analysis. For both inhaled liposomal ciprofloxacin products, the plateau value represents 100% release of the encapsulated drug. The key elements of this IVR method may prove useful for characterization of other liposomal products as well.
    Journal of Pharmaceutical Sciences 11/2013; · 3.01 Impact Factor
  • Source
    [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).
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In vitro drug release evaluation is a very important step toward the quality control of nano- or micro-particular drug delivery systems. However, most quantitative techniques such as high-performance liquid chromatography requires a dialysis membrane to separate the released free drug from these delivery systems, thus are not capable of direct detection and real-time quantification of the drug release kinetics. This study describes, for the first time, a rapid, specific, and direct method for the real-time quantification of in vitro tenofovir (TNF) release from pH-sensitive microparticles using a Varian 400 MHz (1)H nuclear magnetic resonance ((1)H-NMR) spectrometer. Various analytical performance parameters such as linearity, precision, accuracy, limit of quantification, limit of detection, and robustness were validated according to International Conference on Harmonization (ICH) guidelines. The in vitro release of TNF from microparticles in both simulated vaginal fluid (VFS) and the mixture of VFS and simulated semen fluid was monitored and quantified in real time using (1)H-NMR. The capability of real-time quantification of in vitro drug release from microparticles not only provides a more accurate prediction of its biological behavior in vivo, but is also independent of potential interference from the dialysis membrane.
    Journal of Pharmaceutical Sciences 04/2014; 103(4):1170-7. · 3.13 Impact Factor

Full-text

Download
126 Downloads
Available from
May 29, 2014