Mechanisms of formation and disintegration of alginate beads obtained by prilling
Introduction
The need to control drug release or to overcome drug stability problems in oral delivery has been a stimulus for the development of microencapsulated products. Several physical methods for microencapsulation such as spray drying, fluid bed coating, electrostatic deposition or extrusion have been investigated for the manufacturing of particles of controlled dimension and morphology. In the last few years, the technique known as laminar jet break-up or prilling has raised considerable interest because of the possibility to obtain microparticles for drug delivery of a narrow dimensional range and high encapsulation efficiency (Sakai and Hoshino, 1980, Matsumoto et al., 1986, Brandenberg and Widmer, 1998). These microparticles or beads are produced by breaking apart a laminar jet of polymer solution into a row of mono-sized drops by means of a vibrating nozzle device. The resultant droplets fall into a polymer gelation solution in which they are solidified as beads. This technique has shown attractive applications in different fields, including cell immobilization, owing to its mild operative conditions (Hunik and Tramper, 1993, Brandenberg and Widmer, 1998, Serp et al., 2000, Koch et al., 2003).
Sodium alginate is a biodegradable and bioadhesive polymer. Some pharmacopoeia monographs are devoted to this polysaccharide, stating the quality requirements for its application in pharmaceutical preparations (Fundueanu et al., 1999, Koch et al., 2003). Since sodium alginate is capable of producing beads by ionotropic gelation in the presence of bivalent cations, it has frequently been proposed for encapsulating drugs and biological materials (Orive et al., 2002, Ueng et al., 2004).
Several papers can be found in the literature on the use of sodium alginate for bead production (Thu et al., 1996, Kikuchi and Okano, 2002, Schwinger et al., 2002, Tonnesen and Karlsen, 2002, Koyama and Seki, 2004). The sodium alginate used in these studies was of a narrow range molecular weight with a well-characterized viscosity. No paper reports the use of pharmacopoeia-grade sodium alginate for the manufacturing of beads.
The aim of this work was to study the effects of relevant process variables on the characteristics of compendial sodium alginate beads manufactured by laminar jet break-up technology. In particular, polymer concentration, solution viscosity and jet flow rate were considered. The objectives of the present work were to identify the mechanisms of formation and disintegration of alginate beads obtained by prilling.
Section snippets
Materials and methods
Sodium alginate European Pharmacopoeia 4 (Carlo Erba, Milan, Italy) was used as purchased, without further purification. Water content (5%, w/w) was determined by thermo-gravimetric analysis (TG50-Mettler Toledo, Columbus, OH, USA). The viscosity of sodium alginate solutions was measured by rotational rheometer (Bohlin Instruments Division, UK) where a cone–plate combination (CP 4/40) was used as measuring system.
Sodium alginate solution density was determined by glass picnometer in accordance
Effect of sodium alginate concentration and viscosity on hydrated bead micromeritics
The effects of concentration, viscosity and volumetric flow rate of the sodium alginate solution on bead micromeritics were studied. A first series of prilling experiments was performed, in accordance with literature data (Schneider and Hendriks, 1964, Sakai et al., 1985), in operating conditions inducing the jet break-up of a sodium alginate solution at 0.5% (w/w). Thus, beads from sodium alginate solutions at different concentrations from 0.5 to 2.75% (w/w) were produced using the nozzle of
Conclusions
Using solutions of compendial sodium alginate and the selected jet break-up operating conditions, we found that the beads are produced according to two different mechanisms depending on the solution properties (viscosity, density and surface activity) and jet rate. In particular, large beads were manufactured when the formation mechanism was dripping assisted by vibration. In contrast, when the mechanism was laminar solution jet break-up, the size of beads was small. Both flow regimes, i.e.
Acknowledgments
The authors would like to thank Professor C. Bonferoni and Professor Carla Caramella (University of Pavia) for their help in the rheological experiments.
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