Formulation Design of Self-Microemulsifying Drug Delivery Systems for\ud Improved Oral Bioavailability of Celecoxib

摘要

Celecoxib is a hydrophobic and highly permeable drug belonging to class II of biopharmaceutics classification\udsystem. Low aqueous solubility of celecoxib leads to high variability in absorption after oral administration.\udCohesiveness, low bulk density and compressibility, and poor flow properties of celecoxib impart complications\udin it’s processing into solid dosage forms. To improve the solubility and bioavailability and to get faster onset of\udaction of celecoxib, the self-microemulsifying drug delivery system (SMEDDS) was developed. Composition of\udSMEDDS was optimized using simplex lattice mixture design. Dissolution efficiency, t85%, absorbance of diluted\udSMEDDS formulation and solubility of celecoxib in diluted formulation were chosen as response variables. The\udSMEDDS formulation optimized via mixture design consisted of 49.5% PEG-8 caprylic/capric glycerides, 40.5%\udmixture of Tween20 and Propylene glycol monocaprylic ester (3 : 1) and 10% celecoxib, which showed signifi-\udcantly higher rate and extent of absorption than conventional capsule. The relative bioavailability of the\udSMEDDS formulation to the conventional capsule was 132%. The present study demonstrated the suitability of\udmixture design to optimize the compositions for SMEDDS. The developed SMEDDS formulations have the potential\udto minimize the variability in absorption and to provide rapid onset of action of celecoxib.