Improving the Oral Absorption of Celecoxib via Solid Self-Microemulsion Drug Delivery System: Preparation and In Vitro/In Vivo Evaluation

Abstract

Improving the Oral Absorption of Celecoxib via Solid Self-Microemulsion Drug Delivery SystemCelecoxib is a specific cyclooxygenase-2 inhibitor with poor solubility and low bioavailability. A solid selfmicroemulsifying drug delivery system of celecoxib was therefore developed to improve in vitro drug solubility and in vivo absorption. Solubility testing, compatibility testing and pseudo-ternary phase diagrams were employed in the design. Morphological observation, droplet size and in vitro release were used to characterize the formulation. The optimized celecoxib-liquid self-microemulsifying drug delivery system was determined as 10 % of celecoxib, 25 % of medium chain triglycerides, 56.25 % of emulsifier and 18.75 % of Transcutol HP. 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay was used to investigate the cytoxicity of active pharmaceutical ingredients, blank self-microemulsion and celecoxib liquid self-microemulsifying drug delivery system on Caco-2 cells. Celecoxib solid self-microemulsifying drug delivery system was prepared with Neusilin-US2 as a solid adsorbent and characterized using scanning electron microscopy, X-ray, Fourier-transform infrared spectroscopy, differential scanning calorimetry and in vitro release. Celecoxib liquid self-microemulsifying drug delivery system had a clear and transparent light-yellow appearance with average particle size of about 22.68 nm, zeta potential of -31.92 mv, and polydisperse coefficient of 0.141. 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide results showed that the formulations virtually had no cytotoxic effect on the cells. The results also showed that celecoxib existed in an amorphous state in celecoxib-solid self-microemulsifying drug delivery system, and the celecoxib-liquid self-microemulsifying drug delivery system and celecoxib-solid-self-microemulsifying drug delivery system had a dissolution degree of more than 90 % in different media with good stability. The pharmacokinetic studies showed that the area under curve of the liquid self-microemulsifying drug delivery system and self-microemulsifying drug delivery system increased by 6.59 and 6.37 folds, respectively, compared with celecoxib suspension. The findings showed that the developed solid self-microemulsion formulations improved the bioavailability of the drug with no cytotoxicity, hence the formulation can serve as a promising carrier for the oral delivery of celecoxib.