title: Evaluation of ophthalmic suspensions using surface tension.
abstract: Uniformity and precision of single dose are required for ophthalmic suspensions including water-insoluble ingredients. Solid sediments formed after standing still must be immediately re-dispersible and distributed homogeneously before use. However, selection of an appropriate water-soluble polymer as suspending agent is a challenging problem. In this report, the relationship between the surface tension and the re-dispersibility of suspensions was investigated. The surface tension of 0.1 w/v% fluorometholone suspensions began to decline from 74 mN/m at 0.0001 w/v% of hydroxypropylmethylcellulose (HPMC) and became almost constant at 52 mN/m at 0.01 w/v% of HPMC. Re-dispersion time was less than 4 s when HPMC was present at concentrations between 0.0001 w/v% and 0.01 w/v%. At these concentrations, aggregation of suspended particles was not observed. When indomethacin suspensions at 1.0 w/v% concentration were used, the surface tension began to decline from 73 mN/m at 0.0005 w/v% HPMC and became constant at 50 mN/m at 0.005 w/v% HPMC. The suspension also showed good re-dispersibility, and a uniform suspension was obtained between 0.0005 w/v% and 0.005 w/v% of HPMC. The time required for re-dispersion was less than 17 s. The change of surface tension showed a good correlation with the concentration of HPMC in ophthalmic suspensions having good re-dispersibility. Measurement of the surface tension of suspensions provided the optimal concentration of the water-soluble polymers for the suspensions of well re-dispersible characteristics. Evaluation of ophthalmic suspension using surface tension is a good strategy for formulation of suspending pharmaceutical products in the ophthalmic area.
authors.affiliation: Senju Pharmaceutical Co. Ltd., Osaka, Japan. yasueda@senju.co.jp
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Yasueda
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Inada
authors.forename: Keiichi
authors.initials: K
authors.lastname: Matsuhisa
authors.forename: Hideo
authors.initials: H
authors.lastname: Terayama
authors.forename: Akira
authors.initials: A
authors.lastname: Ohtori
mesh_terms: D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005469:Fluorometholone / Q000737:chemistry; D007213:Indomethacin / Q000737:chemistry; D007785:Lactose / Q000031:analogs & derivatives* / Q000737:chemistry; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D009883:Ophthalmic Solutions / Q000737:chemistry*; D010078:Oxazines; D019999:Pharmaceutical Solutions / Q000737:chemistry*; D013500:Surface Tension
chemical_list: D009883:Ophthalmic Solutions; D010078:Oxazines; D019999:Pharmaceutical Solutions; D008747:Methylcellulose; C071191:MK 458; D007785:Lactose; D005469:Fluorometholone; D007213:Indomethacin