The use of biodegradable polymeric carriers for the drug delivery systems has gained a wide interest, mainly for their biocompatibility and, among the microparticulate systems, microspheres show a special importance for providing local as well as temporal controlled release of the drug. Different types of polymers are encountered in the literature used to this purpose. In the case of the release of diclofenac are available: poly-3-caprolactone, poly-/vinylalcohol, poly-lactide-co-glycolide. Also natural polymers found their application in this field: albumin, alginate, carboxymethyl-cellulose, chitosan. The preparation and characterization of the samples are quite similar in most cases. The anti-inflammatory drug (as sodium salt) is dissolved in an aqueous solution containing the soluble polymer and, in the case of carboxylate-containing polymers (alginate, carboxymethyl cellulose), the formation of microspheres was obtained by the addition of Ca2+ or Al3+: the hydrophilic colloids interact with metal ions to form crosslinked insoluble complexes, that precipitate incorporating the drug. In this paper, we prepared microspheres of alginate containing sodium diclofenac and examined the different influence of Ca2+ or Al3+ ions on the microsphere morphology and the influence of different amounts of chitosan on the release of diclofenac. Among polyanionic polymers alginate has been widely studied and applied for the possibility to modulate the release, according to the properties of its carboxyl groups as well as its biodegradability and absence of toxicity. Also chitosan finds wide applications in pharmaceutical technology as tablet disintegrant, for the production of controlled release solid dosage forms or for improvement of drug dissolution Diclofenac is a suitable candidate for incorporation into microspheres to minimize its adverse effect after oral administration; in fact, alginate microspheres containing diclofenac start to release the drug after the pH of the environment increases above 7, by-passing the gastric environment and avoid direct contact between the drug and the gastric mucosa. RESULTS AND DISCUSSION Morphology - Figure 1 shows a microsphere prepared adding Ca2+, exhibiting acceptable sphericity and a notable surface porosity, with a shape factor greater than 0.80 in all the cases. This morphology was found independent of the starting composition, provided that Ca2+ ions were the gelifying agent (left). The aspect and morphology of the particulates prepared with Al3+ ions is different (right): no formulation enabled the formation of a spherical morphology; on the contrary, the particles are flattened, disk-shaped with a collapsed center. The surface appears smooth and little porous with a shape factor less than 0.80. The trivalent ions cause more points of aggregation between two contiguous alginate chains, binding them so strictly and quickly that, as a consequence, there is no time to get spherical forms, during their formation and the morphology of the particle recalls the feature of a drop touching a water surface. For the preparation of chitosan treated alginate beads containing sodium diclofenac, we dissolved sodium diclofenac in the aqueous solution of sodium alginate. The addition of the divalent (or trivalent) ions produced a partial neutralization of carboxylate groups present on the alginate chain, forming an insoluble (but permeable) transitory thin gelatinous film: Ionic gelation is the result of the formation of an ‘egg box’ between facing units of two different chains and depends on the inorganic ion/alginate ratio...
Microencapsulation of sodium diclofenac in arginate/chitosan particulate systems
FINI, ADAMO
2005
Abstract
The use of biodegradable polymeric carriers for the drug delivery systems has gained a wide interest, mainly for their biocompatibility and, among the microparticulate systems, microspheres show a special importance for providing local as well as temporal controlled release of the drug. Different types of polymers are encountered in the literature used to this purpose. In the case of the release of diclofenac are available: poly-3-caprolactone, poly-/vinylalcohol, poly-lactide-co-glycolide. Also natural polymers found their application in this field: albumin, alginate, carboxymethyl-cellulose, chitosan. The preparation and characterization of the samples are quite similar in most cases. The anti-inflammatory drug (as sodium salt) is dissolved in an aqueous solution containing the soluble polymer and, in the case of carboxylate-containing polymers (alginate, carboxymethyl cellulose), the formation of microspheres was obtained by the addition of Ca2+ or Al3+: the hydrophilic colloids interact with metal ions to form crosslinked insoluble complexes, that precipitate incorporating the drug. In this paper, we prepared microspheres of alginate containing sodium diclofenac and examined the different influence of Ca2+ or Al3+ ions on the microsphere morphology and the influence of different amounts of chitosan on the release of diclofenac. Among polyanionic polymers alginate has been widely studied and applied for the possibility to modulate the release, according to the properties of its carboxyl groups as well as its biodegradability and absence of toxicity. Also chitosan finds wide applications in pharmaceutical technology as tablet disintegrant, for the production of controlled release solid dosage forms or for improvement of drug dissolution Diclofenac is a suitable candidate for incorporation into microspheres to minimize its adverse effect after oral administration; in fact, alginate microspheres containing diclofenac start to release the drug after the pH of the environment increases above 7, by-passing the gastric environment and avoid direct contact between the drug and the gastric mucosa. RESULTS AND DISCUSSION Morphology - Figure 1 shows a microsphere prepared adding Ca2+, exhibiting acceptable sphericity and a notable surface porosity, with a shape factor greater than 0.80 in all the cases. This morphology was found independent of the starting composition, provided that Ca2+ ions were the gelifying agent (left). The aspect and morphology of the particulates prepared with Al3+ ions is different (right): no formulation enabled the formation of a spherical morphology; on the contrary, the particles are flattened, disk-shaped with a collapsed center. The surface appears smooth and little porous with a shape factor less than 0.80. The trivalent ions cause more points of aggregation between two contiguous alginate chains, binding them so strictly and quickly that, as a consequence, there is no time to get spherical forms, during their formation and the morphology of the particle recalls the feature of a drop touching a water surface. For the preparation of chitosan treated alginate beads containing sodium diclofenac, we dissolved sodium diclofenac in the aqueous solution of sodium alginate. The addition of the divalent (or trivalent) ions produced a partial neutralization of carboxylate groups present on the alginate chain, forming an insoluble (but permeable) transitory thin gelatinous film: Ionic gelation is the result of the formation of an ‘egg box’ between facing units of two different chains and depends on the inorganic ion/alginate ratio...I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
