DESIGN OF MICROENCAPSULATED CHITOSAN MICROSPHERES FOR COLONIC DRUG-DELIVERY

Among the different approaches to achieve colon-selective drug deliver y, the use of polymers, specifically biodegraded by colonic bacteria, holds great promise. In this work a new system which combines specific biodegradability and pH-dependent release is presented. The system co nsists of chitosan (CS) microcores entrapped within acrylic microspher es. Sodium diclofenac (SD), used as a model drug, was efficiently entr apped within CS microcores using spray-drying and then microencapsulat ed into Eudragit(R) L-100 and Eudragit S-100 using an oil-in-oil solve nt evaporation method. The size of the CS microcores was small (1.8-2. 9 mu m) and they were efficiently encapsulated within Eudragit microsp heres (size between 152 and 223 mu m) forming a multireservoir system. Even though CS dissolves very fast in acidic media, at pH 7.4, SD rel ease from CS microcores was delayed, the release rate being adjustable (50% dissolved within 30-120 min) by changing the CS molecular weight (MW) or the type of CS salt. Furthermore, by coating the CS microcore s with Eudragit, perfect pH-dependent release profiles were attained. No release was observed at acidic pHs, however, when reaching the Eudr agit pH solubility, a continuous release for a variable time (8-12 h) was achieved. A combined mechanism of release is proposed, which consi ders the dissolution of the Eudragit coating, the swelling of the CS m icrocores and the dissolution of SD and its further diffusion through the CS gel cores. In addition, infrared (IR) spectra revealed that the re was an ionic interaction between the amine groups of CS and the car boxyl groups of Eudragit, which provided the system with a new element for controlling the release. In conclusion, this work presents new ap proaches for the modification of CS as well as a new system with a gre at potential for colonic drug delivery. (C) 1998 Elsevier Science B.V.