Topical use of chitosan in ophthalmology: tolerance assessment and evaluation of precorneal retention

• Published in: International journal of pharmaceutics Vol. 180; no. 2; pp. 185 - 193
• Main Authors: Felt, O., Furrer, P., Mayer, J.M., Plazonnet, B., Buri, P., Gurny, R.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15.04.1999; Elsevier
• Subjects: Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacokinetics; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biocompatible Materials - administration & dosage; Biocompatible Materials - adverse effects; Biocompatible Materials - pharmacokinetics; Biological and medical sciences; Chitin - administration & dosage; Chitin - adverse effects; Chitin - analogs & derivatives; Chitin - pharmacokinetics; Chitosan; Cornea - diagnostic imaging; Cornea - drug effects; Cornea - metabolism; Gamma Cameras; Gamma scintigraphy; Gels; General pharmacology; Hydrogen-Ion Concentration; Male; Medical sciences; Microscopy, Confocal; Ocular tolerance; Ophthalmic Solutions; Ophthalmoscopy; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Precorneal retention; Rabbits; Radionuclide Imaging; Radiopharmaceuticals - administration & dosage; Radiopharmaceuticals - pharmacokinetics; Technetium Tc 99m Pentetate - administration & dosage; Technetium Tc 99m Pentetate - pharmacokinetics; Tobramycin - administration & dosage; Tobramycin - pharmacokinetics; Viscosity; Ocular tolerance; Chitosan; Precorneal retention; Gamma scintigraphy; Ophthalmoscopy; Viscosity; Pharmaceutical technology; Toxicity; Rabbit; Drug carrier; Scintigraphy; Lagomorpha; Retention time; Eye drop; Colloidal gel; Eye; Vertebrata; Antibiotic; Mammalia; Aminoglycoside; Animal; Dosage form; Ophthalmology; Tobramycin; Antibacterial agent; Topical administration
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(99)00003-4

The mucoadhesive polysaccharide chitosan was evaluated as a potential component in ophthalmic gels for enabling increased precorneal drug residence times. This cationic vehicle was expected to slow down drug elimination by the lacrymal flow both by increasing solution viscosity and by interacting with the negative charges of the mucus. The molecular weight ( M w) and concentration of polysaccharide were studied in four types of chitosan as parameters that might influence ocular tolerability and precorneal residence time of formulations containing tobramycin as therapeutic agent. An ocular irritation test, using confocal laser scanning ophthalmoscopy (CLSO) combined with corneal fluorescein staining, clearly demonstrated the excellent tolerance of chitosan after topical administration onto the corneal surface. Gamma scintigraphic data showed that the clearance of the formulations labelled with 99mTc-DTPA was significantly delayed in the presence of chitosan with respect to the commercial collyrium (Tobrex ®), regardless of the concentration and of the molecular weight of chitosan in solution. At least a 3-fold increase of the corneal residence time was achieved in the presence of chitosan when compared to Tobrex ®.