Abstract
Ketorolac is a non-steroidal anti-inflammatory drug used in the treatment of pain. However, it has side effects including gastrointestinal (GI) irritation when administered orally. The oral administration of conventional oral dosage forms of ketorolac can cause serious gastrointestinal side effects and gastric irritation due to dose dumping. The objective of this study was to prepare enteric matrix pellets of the drug that lower the risk of side effects by the formulation of Eudragit / microcrystalline cellulose (Avicel PH 101) pellets using extrusion / spheronization technique. Moreover, mixer torque rheometer was used to quantitatively determine the suitable moisture content in the pastes before the extrusion process. The produced pellets were characterized for their ketorolac content, particle size, shape and dissolution profile. Studies on the effect of additives (A vice! and PVP) on Eudragit rheological properties revealed that the magnitude of torque lowered as the Avicel ratio increased, a fact that reflected on the roundness of the produced pellets. The release of the drug is controlled by the Eudragit/ Avicel ratio. In some formulations, in acidic medium, the release of the drug was less than 10% after 2 hrs, while it is completely released within 60-120 min after changing dissolution medium to phosphate buffer (pH 6.8).
In conclusion, the manufactured pellets delayed drug release rates as well as it successfully passed the USP requirements for enteric delayed release articles, which might be beneficial in lowering the risk of side effects as an advantage of the pellets as drug delivery system without the need for tedious enteric coating process.