Fabrication and in-vitro Evaluation of Ketotifen Fumarate-loaded PLGA Nanoparticles as a Sustained Delivery System

Ketotifen fumarate is a non-bronchodilator anti-asthmatic drug which inhibits the effects of certain endogenous substances known to be inflammatory mediators, and thereby exerts antiallergic activity. The present study describes the formulation of a sustained release nanoparticle (NP) drug delivery system containing ketoftifen, using poly (D,L lactide-co-glycolide) acid (PLGA). Biodegradable NPs were prepared using 50 : 50 PLGA by a water in-oil-in-water (w/o/w) double emulsion-solvent evaporation procedure and characterized for drug content, DSC (differential scanning calorimetry, XRD (X-ray diffractionl), FTIR (Fourier transform spectroscopy), particle size , surface morphology using scanning electron microscopy, and drug release rate. The effects of different drug-to-polymer ratios on the characteristics of the NPs were investigated. NPs prepared were spherical with a smooth surface. Size of NPs was dependent on the concentration of polymer (10 mg/mL, 754.6 nm). Increasing the external organic phase volume (primary emulsion) resulted in larger particles with higher encapsulation efficiency (55%). The best drug to polymer ratio in the NP was F3 (1:10 ratio) which showed loading efficiency of 55%, and mean particle size of 754.6 nm, respectively. The FTIR, XRPD, and DSC results ruled out any chemical interaction between the drug and PLGA. The NPs prepared with low ratio of drug to polymer (1:5) F1 formulation showed faster dissolution rate than those with high drug to polymer ratio (1:10) F3 formulation. In conclusion, by selecting an appropriate level of the investigated parameters, spherical NPs with encapsulation efficiencies higher than 55% and a prolonged drug release over 24h (73.67-90.05%) were obtained.