Article

Development of a dialysis in vitro release method for biodegradable microspheres.

University of Kentucky College of Pharmacy, Lexington, KY 40536, USA.
AAPS PharmSciTech (Impact Factor: 1.78). 02/2005; 6(2):E323-8. DOI: 10.1208/pt060242
Source: PubMed

ABSTRACT The purpose of this research was to develop a simple and convenient in vitro release method for biodegradable microspheres using a commercially available dialyzer. A 25 KD MWCO Float-a-Lyzer was used to evaluate peptide diffusion at 37 degrees C and 55 degrees C in different buffers and assess the effect of peptide concentration. In vitro release of Leuprolide from PLGA microspheres, having a 1-month duration of action, was assessed using the dialyzer and compared with the commonly used sample and separate method with and without agitation. Peptide diffusion through the dialysis membrane was rapid at 37 degrees C and 55 degrees C in all buffers and was independent of peptide concentration. There was no detectable binding to the membrane under the conditions of the study. In vitro release of Leuprolide from PLGA microspheres was tri-phasic and was complete in 28 days with the dialysis technique. With the sample and separate technique, linear release profiles were obtained with complete release occurring under conditions of agitation. Diffusion through the dialysis membrane was sufficiently rapid to qualify the Float-a-Lyzer for an in vitro release system for microparticulate dosage forms. Membrane characteristics render it useful to study drug release under real-time and accelerated conditions.

1 Bookmark
 · 
356 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Due to their particle size in the submicrometer range, lipid nanoparticles are suitable for parenteral administration. In order to obtain information on their potential in vivo performance, a simple and effective in vitro assay to evaluate the drug release behavior of such particles is required. This study compares the use of different experimental setups for this purpose. Lipid nanoparticles from trimyristin which were loaded with fluorescent lipophilic drug models (a temoporfin and Nile red) were used as donor particles. The transfer of the two drug models to multilamellar vesicles (MLV) and emulsion droplets as lipophilic acceptor compartments was examined. The determination of the transferred substance was performed either after separation by centrifugation or by an in situ flow cytometric technique. The transfer of temoporfin was slow to the acceptor MLV and very rapid to the acceptor emulsion. With both acceptors, the transfer of temoporfin stopped at a concentration much lower than the theoretical equilibrium values. The transfer of the less lipophilic drug Nile red was very rapid to both acceptors with equilibrium concentrations close to the expected values. The transfer results of temoporfin especially to the acceptor MLV obtained with the two detection techniques were comparable while the centrifugation technique indicated an apparently higher Nile red transfer rate than the flow cytometric technique. Both techniques are equally suitable to study the transfer of temoporfin, while the flow cytometric technique is advantageous to measure the very rapid transfer of Nile red.
    AAPS PharmSciTech 08/2014; 15(6). DOI:10.1208/s12249-014-0179-7 · 1.78 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To prepare stearic acid-based lopinavir (LPV) loaded solid lipid nanoparticles (SLNs) using a hybrid design and compare in-vivo performance of optimized formulation with marketed LPV/ritonavir (RTV) coformulation. LPV SLNs were prepared by hot melt emulsion technique and optimized using Plackett-Burman design and Box-Behnken design. Physical characterization studies were conducted for the optimized SLNs. Comparative oral pharmacokinetic studies and tissue distribution studies of optimized SLNs and LPV/RTV coformulation were done in Wistar rats. In-vitro metabolic stability and intestinal permeability studies for LPV SLNs were undertaken to elucidate the mechanism involved in the pharmacokinetic improvement of LPV. Optimized SLNs exhibited nanometeric size (223 nm) with high entrapment efficiency (83%). In-vitro drug release study of SLNs showed biphasic sustained release behaviour. Significant increase in oral bioavailability of LPV from LPV SLNs (5 folds) and LPV/RTV coformulation (3.7 folds) was observed as compared with free LPV. LPV SLNs showed better tissue distribution of LPV in HIV reservoirs than LPV/RTV coformulation. In-vitro studies demonstrated that SLNs provided metabolic protection of LPV and were endocytosized during absorption. SLNs enhanced oral bioavailability and improved distribution profile of LPV to HIV reservoirs and hence could be better alternative to LPV/RTV coformulation.
    02/2014; DOI:10.1111/jphp.12217
  • [Show abstract] [Hide abstract]
    ABSTRACT: Incompatible interactions of polymers with active chemical entity offer variable challenges in drug delivery kinetics. This study focuses on development of hybrid polymer blend nanoparticles with amphiphilic (Poly Vinyl Pyrrolidone) and hydrophobic (Ethyl cellulose and Eudragit RSPO) polymers to encapsulate maximum drug without significant incompatibility. Optimized nanoparticles developed using Acyclovir model drug exhibited 80% entrapment with size and surface charge of 100 nm and +26 mV, respectively. Spherical morphology and solid state transition of drug from crystalline to amorphous in nanoparticles was confirmed by SEM and XRD analysis. pH independent in-vitro drug release was observed in four different media with initial burst release followed by sustained release for >12 h. Statistically significant difference (P < 0.05) was observed in percentage of drug release from each formulation in different media. H-bonding and hydrophobic interactions between drug and polymer (FTIR, TG-DTA analysis and Makoid–Banakar Kinetics) and diffusion of drug from matrix nanospheres followed by pore transport were the key factors for effective drug release kinetics. Uptake of nanoparticles by corneal epithelial cells was more prominent within 30 min, however viability of cells was not altered significantly. Release kinetics and interactions studies revealed the suitability of polymer blend nanoparticles for better encapsulation and sustained release of the drug.
    Journal of the Taiwan Institute of Chemical Engineers 01/2015; DOI:10.1016/j.jtice.2014.12.036 · 2.64 Impact Factor

Full-text (2 Sources)

Download
69 Downloads
Available from
Jun 13, 2014