Preparation and evaluation of celecoxib-loaded proliposomes with high lipid content

Abstract

A novel proliposomal formulation for improved oral delivery of celecoxib (CXB) was developed using a solid dispersion technique. CXB, soy phosphatidylcholine (SPC), sorbitol, and poloxamer 188 were dissolved in a water/ethanol binary solvent system. Subsequent solvent-evaporation and lyophilization steps produced CXB-loaded proliposomes (CXBPLs) with high lipid content (as SPC, ≈20% [w/w]). Powder X-ray diffractometry and differential scanning calorimetry analyses revealed that the physical state of CXB was transformed from crystalline to amorphous after the preparation process. Reconstitution of CXBPLs with gentle shaking by hand generated CXB-loaded liposomes with nano-sized mean diameter, negative zeta potential, vesicular-shaped morphology, and high CXB entrapment efficiency (≈84.7%). CXBPLs exhibited improved dissolution rate and permeability compared with free CXB and Celebrex (a commercial product of CXB). In the pharmacokinetic study performed in rats, the CXBPL-treated group showed a 1.7-fold increase in the bioavailability of CXB compared with the free CXB-treated group (p < 0.05). The histological observation with hematoxylin and eosin staining demonstrated no additional detrimental effect of CXBPLs on the intestinal epithelia of rats compared with that of free CXB. These results suggest that the developed proliposomes provide an efficient and safe way of enhancing the oral bioavailability of poorly water-soluble drugs.