Development and characterization of naproxen-chitosan solid systems with improved drug dissolution properties.
The solubilizing and amorphizing properties toward naproxen (a poorly water-soluble antiinflammatory drug) of chitosan, an emerging pharmaceutical biopolymer, have been investigated. Solid binary systems at different drug/polymer ratios have been prepared according to different techniques (mixing, cogrinding, kneading, coevaporation) using chitosan at low (CS-L(w)) and medium (CS-M(w)) molecular weight, and tested for dissolution properties. Drug-carrier interactions were investigated in both the liquid and solid state, by phase solubility analysis, differential scanning calorimetry, X-ray powder diffractometry, FT-IR spectroscopy, and scanning electron microscopy. Drug dissolution parameters improved with increasing the polymer amount in the mixture, reaching the highest values at the 1:9 (w/w) drug/polymer ratio, and CS-L(w) was more efficacious than CS-M(w). Cogrinding was the most effective technique, showing the strongest amorphizing effect toward the drug and enabling an increase of more than ten times its relative dissolution rate. Coground mixtures at 3:7 (w/w) drug/polymer ratio were able to give directly compressed tablets which maintained unchanged the improved drug dissolution properties. Enhancer dissolution properties combined with its direct compression feasibility and antiulcerogenic action make CS-L(w) an optimal carrier for developing fast-release oral solid dosage forms of naproxen.
Dipartimento di Scienze Farmaceutiche, Facoltà di Farmacia, Università di Firenze, Via Gino Capponi 9, 50121 Firenze, Italy. mura@farmfi.scifarm.unifi.it
Paola
P
Mura
Naima
N
Zerrouk
Natascia
N
Mennini
Francesca
F
Maestrelli
Chantal
C
Chemtob
D000277:Adjuvants, Pharmaceutic / Q000737:chemistry; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002686:Chitin / Q000031:analogs & derivatives* / Q000737:chemistry*; D048271:Chitosan; D004337:Drug Carriers; D004339:Drug Compounding; D008855:Microscopy, Electron, Scanning; D008970:Molecular Weight; D009288:Naproxen / Q000737:chemistry*; D019999:Pharmaceutical Solutions; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D013997:Time Factors; D014961:X-Ray Diffraction
D000277:Adjuvants, Pharmaceutic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D019999:Pharmaceutical Solutions; D002686:Chitin; D009288:Naproxen; D048271:Chitosan