Formulation, characterization and pulmonary deposition of nebulized celecoxib encapsulated nanostructured lipid carriers.
The aim of the current study was to encapsulate celecoxib (Cxb) in the nanostructured lipid carrier (Cxb-NLC) nanoparticles and evaluate the lung disposition of nanoparticles following nebulization in Balb/c mice. Cxb-NLC nanoparticles were prepared with Cxb, Compritol, Miglyol and sodium taurocholate using high-pressure homogenization. Cxb-NLC nanoparticles were characterized for physical and aerosol properties. In-vitro cytotoxicity studies were performed with A549 cells. The lung deposition and pharmacokinetic parameters of Cxb-NLC and Cxb solution (Cxb-Soln) formulations were determined using the Inexpose system and Pari LC star jet nebulizer. The particle size and entrapment efficiency of the Cxb-NLC formulation were 217+/-20nm and >90%, respectively. The Cxb-NLC released the drug in controlled fashion, and in-vitro aerosolization of Cxb-NLC formulation showed an FPF of 75.6+/-4.6%, MMAD of 1.6+/-0.13microm and a GSD of 1.2+/-0.21. Cxb-NLC showed dose and time dependent cytotoxicity against A549 cells. Nebulization of Cxb-NLC demonstrated 4 fold higher AUC(t)/D in lung tissues compared to the Cxb-Soln. The systemic clearance of Cxb-NLC was slower (0.93l/h) compared to the Cxb-Soln (20.03l/h). Cxb encapsulated NLC were found to be stable and aerodynamic properties were within the respirable limits. Aerosolization of Cxb-NLC improved the Cxb pulmonary bioavailability compared to solution formulation which will potentially lead to better patient compliance with minimal dosing intervals.
College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA.
Ram R
RR
Patlolla
Mahavir
M
Chougule
Apurva R
AR
Patel
Tanise
T
Jackson
Prasad N V
PN
Tata
Mandip
M
Singh
D000336:Aerosols; D000818:Animals; D001682:Biological Availability; D000068579:Celecoxib; D002626:Chemistry, Pharmaceutical; D004304:Dosage Forms; D005240:Feasibility Studies; D008055:Lipids / Q000008:administration & dosage; D008168:Lung / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage; D049329:Nanostructures; D010316:Particle Size; D011720:Pyrazoles; D013449:Sulfonamides
D000336:Aerosols; D004304:Dosage Forms; D008055:Lipids; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib