Celecoxib Nanoformulations with Enhanced Solubility, Dissolution Rate, and Oral Bioavailability: Experimental...

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Nanotechnology

Background:

• Celecoxib (CXB), a Biopharmaceutical Classification System (BCS) Class II drug, exhibits poor water solubility and limited oral bioavailability.
• Traditional oral administration of CXB results in variable absorption due to its physicochemical properties.
• Dry co-milling offers an industrially applicable method to overcome solubility and bioavailability challenges.

Purpose of the Study:

• To develop and optimize celecoxib (CXB) nanoformulations using dry co-milling technology.
• To enhance solubility, dissolution rate, and oral bioavailability of CXB through a Quality by Design (QbD) approach.
• To evaluate the in vitro and in vivo performance of the optimized CXB nanoformulations.

Main Methods:

• Development of CXB nanoformulations via dry co-milling with povidone (PVP), mannitol (MAN), and sodium lauryl sulfate (SLS).
• Quality by Design (QbD) principles including Ishikawa diagrams, Plackett-Burman, Central Composite Design (CCD), and Bayesian Optimization (BO) for risk assessment and optimization.
• Comprehensive characterization including physical analysis, intrinsic dissolution rate, solubility, stability, dissolution, permeability, and oral pharmacokinetic studies in rats.

Main Results:

• Optimized co-milled CXB formulations demonstrated significantly enhanced aqueous solubility (over 4.8-fold increase) and dissolution rate (85% dissolved in 20 min).
• In vitro studies confirmed improved dissolution and permeability of the CXB nanoformulations.
• In vivo pharmacokinetic studies in rats showed a 145.2% relative bioavailability compared to Celebrex®, with a faster absorption rate (tmax 3.80 ± 2.28 h vs. 6.00 ± 3.67 h).

Conclusions:

• Dry co-milling is an effective technology for developing celecoxib (CXB) nanoformulations with improved physicochemical and pharmacokinetic properties.
• The developed nanoformulations exhibit enhanced solubility, dissolution, and oral bioavailability, addressing the limitations of pure CXB.
• This QbD-guided approach provides a robust strategy for improving the oral delivery of BCS Class II drugs like celecoxib.