IN-VITRO CHARACTERIZATION AND STABILITY ASSESSMENT OF ATORVASTATIN CALCIUM AND CELECOXIB LIPOSOMAL FORMULATION

Abstract: Background: Atorvastatin calcium and celecoxib are both weakly water-soluble drugs; hence, their oral bioavailability may be limited by poor dissolution and first-pass disposition. Thus, encapsulation within liposomes could potentially modulate their disposition via enhanced dispersion and by providing a controlled-release matrix; however, the possibility of core co-loading should be directly demonstrated. Objective: The objective of the present work was to prepare and characterize the prototype liposomal formulation co-loaded with atorvastatin calcium and celecoxib. Materials and Methods: Five prototype batches of liposomes were prepared using the thin-film hydration method by varying the lecithin concentration while keeping the amount of drugs constant. Physicochemical characterization included determining the pH, particle size, polydispersity index (PDI), entrapment efficiency, and zeta potential, followed by optical microscopic evaluation of liposome morphology, in vitro drug release, and model fitting. Results: Out of the tested batches, the batch F4 was found to be the most promising with an average pH of 7.4 ± 0.33, drug entrapment efficiency of 90 ± 4.36% for atorvastatin calcium and 91 ± 4.56% for celecoxib, mean particle size – 473 nm, PDI – 0.93, and zeta potential – −21.83 mV. Optical microscopic analysis revealed the presence of mostly spherical multivesicular liposomes. In vitro drug release experiments showed that about 40% of the loaded drugs were released during the first 12 h of incubation; moreover, the first-order model was found to have the highest coefficient of determination. Conclusion: This study demonstrated that co-encapsulation of atorvastatin calcium and celecoxib within liposomes could be technically feasible; thus, the present prototype could serve as a controlled-release formulation for oral use. However, the relatively high PDI of the obtained preparation suggests the need for preparing a more homogeneous batch for the further studies. Moreover, additional preclinical trials should be undertaken before its bioavailability, therapeutic efficacy, and thus clinical utility can be established.