Development of sustained release theophylline pellets coated with calcium pectinate

Abstract

We have produced cores containing theophylline, calcium acetate and microcrystalline cellulose by extrusion-spheronization and then applied a coating of calcium pectinate by interfacial complexation. After drying, the coatings were observed by scanning electron microspcopy to be 50-80 μm thick. The type of pectin used, the core size and the coating time all influenced the yield of theophylline in the coated cores. Theophylline release from the uncoated cores was rapid and linear with the square root of time. The in-vitro release of theophylline from the coated cores was tested in water, simulated gastric fluid USP minus pepsin (SGF) and a Tris buffer (pH 7.4). In general, release was essentially constant until 75-80% of the drug was released. The large coated cores released over a period of about 4 h and the small coated cores released over a period of 2 h. Although the coatings swelled more when they were rehydrated in the Tris buffer compared to water and SGF, theophylline release was similar in all the dissolution media. In particular, release was not increased by SGF as may have been expected from studies using a similar polysaccharide sodium alginate. Calcium pectinate coatings are easy to apply, do not require harsh conditions and may yield release profiles which are relatively independent of pH.