Development of colonic 5-ASA beads

Abstract

Introduction Recent studies prove that the number of patients with inflammatory bowel disease is increasing all over the world due to contamination, industrialization and changes in the style of live. Some studies have shown that 5-aminosalicylic acid (5-ASA), an anti-inflammatory agent, must be the election treatment for these pathologies. In recent years, the production of microparticles systems seems to be equally promising to develop dosage forms in order to reduce the dosage frequency (1). On the other hand, the efficacy of this drug in the treatment of inflammatory bowel diseases may be optimized with a controlled release drug delivery system which maximizes topical exposure of the drug to the diseased tissue and minimizes systemic absorption of the drug (2). Therefore, the objective of the present paper is to design an oral multi-unit dosage form containing 5-ASA that protects drug up to colon without causing toxicity. The proposed system consists of beads of several compositions (polymers with different nature and characteristics) introduced in an enteric hard gelatin capsule to obviate the transition across the stomach. Materials and Methods 5 – Aminosalicylic acid (5-ASA) was a gift from Schering Plough (Madrid, España). Eudragit ® FS 30D was received from Degussa Iberia S.A. (Barcelona, España). The following materials were obtained from the indicated suppliers and used as received: alginic acid sodium salt (low viscosity) and calcium chloride anhydrous from Sigma (Barcelona, Spain); chitosan, low molecular weight, from Aldrich Chemical Company (Barcelona, Spain); di-sodium hydrogen phosphate anhydrous, potassium di-hydrogen phosphate, sodium chloride and hydrochloric acid from Panreac Química S.A. (Barcelona, España). Alginate beads were prepared as follows: an alginate solution of 2 % w/v was prepared dissolving the sodium alginate in distilled water under stirring. The drug suspension (0.5 % w/v) was added to the alginate solution. This mix was dropped, from a hypodermic syringe, into 1.4 % w/v CaCl 2 solution. The gel beads, which formed immediately in the CaCl 2 solution, were incubated at room temperature (22 ºC) and in darkness in this solution for 24 h to ensure complete reaction. After this time, the beads were filtered and dried using microwaves (3200 W) during 110 minutes with 10% of power. In order to prepare Eudragit FS 30D/alginate beads, a suspension of the polymer (26% or 13% w/v) was added in the mix previously described under agitation, before dropping over a 1.4% w/v CaCl 2 solution. Finally, the chitosan/alginate beads were elaborated by adding chitosan (0.1, 0.2 and 0.5 % w/v) to distilled water containing 1 % (v/v) acetic acid. The 1.4 % w/v CaCl 2 solution was added to the chitosan solution. An alginate/drug suspension was added to this solution to form the beads. The beads were incubated and dried under the same conditions as described above. Table 1 shows the composition of the different beads formulations.