Development of Etoricoxib-Loaded Chitosan-and PEG-Based Microparticles to Restrain the Brain/Neuro Plasticity Associated Chronic Pain

摘要

Background: In the current investigation, oral multiple-unit microparticulate dosage form is produced with the aim of masking the salty (or bitter) taste of etoricoxib (ETX) by incorporating it into hydrophilic polymers (chitosan and polyethylene glycol (PEG))-based microparticles. Objective: The influence of drug loading on ETX liberation from microparticles, the in vitro anti-inflammatory activity of ETX either in pure powder form or after its incorporation into microparticles and the ETX taste masking by drug-loaded microparticles were studied. Method: A temperature controlled dispersion technique was used to produce ETX-loaded chitosan-and PEG-based microparticles. Microparticles were characterized in solid state for particle size analysis, drug content, drug liberation, infrared spectroscopy, thin-layer chromatography and scanning electron microscopy. The in vitro anti-inflammatory activity of free and encapsulated ETX was assessed via the protein denaturation bioassay study and taste masking check up was performed in human volunteers. Results: Over the tested dissolution time period of 90 min in 0.01 N HCl (pH 2.0), the increase in initial drug loadings (30-90 mg) decreased the ETX liberation (36 ± 2% for 30 mg ETX vs. 19 ± 1% for 90 mg ETX) from microparticles. No detectible interaction between drug and polymer was noticed but the drug was present in an amorphous or a disordered-crystalline state within the polymer network. Furthermore, the microencapsulation of ETX in hydrophilic polymer matrices did not alter its anti-inflammatory activity [50% inhibition (IC_(50)) values of 21 μg/ml and 23 μg/ml were observed respectively for ETX-loaded microparticles and ETX solution after mixing with egg albumin]. Conclusion: The usefulness of this oral microparticulate system in restraining the brain/neuro plasticity associated chronic (or residual) pain occurring at rheumatoid arthritis condition deserves further studies.