Alginate/chitosan particulate systems for sodium diclofenac release

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Abstract

Alginate/chitosan particles were prepared by ionic gelation (Ca2+ and Al3+) for the sodium diclofenac release. The systems were characterized by electron microscopy and differential scanning calorimetry. The ability to release the active substance was examined as a function of some technological parameters and pH of dissolution medium. The release of sodium diclofenac is prevented at acidic pH, while is complete in a few minutes when pH is raised up to 6.4 and 7.2. The alginate/chitosan ratio and the nature of the gelifying cation allow a control of the release rate of the drug. The release mechanism was briefly discussed.

Introduction

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 (Lorenzo-Lamosa et al., 1998, Hari et al., 1996) as well as temporal controlled release of the drug (Donbrow, 1992). 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 (Alonso et al., 2000), poly-/vinylalcohol (Chawla et al., 2000), poly-lactide-co-glycolide (Tuncay et al., 2000a, Tuncay et al., 2000b). Also natural polymers found their application in this field: albumin (Tuncay et al., 2000a, Tuncay et al., 2000b), alginate (Gursoy and Cevik, 2000, Acikgoz et al., 1995), carboxymethyl-cellulose (Arica et al., 1996), chitosan (Lim et al., 1997, McLaughlin et al., 1998). 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 its 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 (Miyazaky et al., 1994, Kas, 1997, Illum, 1998, Sezer and Akbuga, 1999) or for improvement of drug dissolution (Felt et al., 1998, Gupta and Ravi Kumar, 2000).

Diclofenac is a suitable candidate for incorporation into microspheres (Hosny et al., 1998, Gohel and Amin, 1999) 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 (Sabnis et al., 1997), by-passing the gastric environment and avoid direct contact between the drug and the gastric mucosa.

Section snippets

Materials

The following materials were obtained from the indicated suppliers and used as received: sodium alginate (low viscosity; viscosity of 2% solution 25 °C, ≈250 cps), chitosan (Practical grade from crab shell; Sigma, Barcelona, Spain). Calcium chloride hexahydrate, aluminum chloride hexahydrate (Sigma, Barcelona, Spain), di-sodium hydrogen phosphate anhydrous, potassium di-hydrogen phosphate, hydrochloride acid 35% and acetic acid glacial 100% (Merck, Barcelona, Spain), were of the highest purity

Results and discussion

Side effects, mainly at the gastric level, are well known, following oral administration of an NSAID. Therefore the efforts of many researchers have been concerned to solve these problems, through a variety of techniques of protection of the gastric mucosa or alternatively to prevent the NSAID release in this district. In this paper we evaluate the potential utility of natural materials, such as alginate and chitosan in inhibiting sodium diclofenac release in the gastric environment. And since

Acknowledgements

This paper was supported by Italy/Spain Integrated Actions.

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