Biodegradable microparticles as a two-drug controlled release formulation:a potential treatment of inflammatory bowel disease

A multiple unit dosage form for oral delivery based on the microencapsulati on of anti-inflammatory drugs using different biodegradable polymers, poly( epsilon -caprolactone), polylactic acid and poly(lactic-co-glycolic acid), prepared either by the water-in-oil-in-water (w/o/w) or the solid-in-oil-in -water (s/o/w) solvent evaporation method was developed. Microparticles wer e characterized for their size, morphology, encapsulation efficiency and dr ug release. The physical state of drugs and polymers was determined by diff erential scanning calorimetry (DSC), imaging of the particles was performed by scanning electron microscopy and confocal laser scanning microscopy. Su lfasalazine and betamethasone used for the treatment of inflammatory bowel disease, were chosen as model drugs. The microparticles were spherical with diameters in the range of 91 to 258 mum by the w/o/w-method, and in the ra nge of 102 to 277 mum by the s/o/w-method. The encapsulation efficiency (EE ) varied between 11 and 16% for sulfasalazine and 50 and 67% for betamethas one with the w/o/w-method, and between 73 and 79% for sulfasalazine and 60 and 70% for betamethasone with the s/o/w-method. DSC showed no interaction between polymers and drugs, while the drugs were dispersed in the polymer. In vitro release studies showed a controlled release of sulfasalazine and b etamethasone from microparticles prepared by the s/o/w-method; a pronounced burst release of sulfasalazine was observed from microparticles prepared b y the w/o/w-method. (C) 2000 Elsevier Science B.V. All rights reserved.