Evaluation of ophthalmic suspensions using surface tension

Eur J Pharm Biopharm. 2004 Mar;57(2):377-82. doi: 10.1016/S0939-6411(03)00159-0.

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.

MeSH terms

  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical / methods
  • Fluorometholone / chemistry
  • Indomethacin / chemistry
  • Lactose / analogs & derivatives*
  • Lactose / chemistry
  • Methylcellulose / analogs & derivatives*
  • Methylcellulose / chemistry
  • Ophthalmic Solutions / chemistry*
  • Oxazines
  • Pharmaceutical Solutions / chemistry*
  • Surface Tension

Substances

  • Ophthalmic Solutions
  • Oxazines
  • Pharmaceutical Solutions
  • Methylcellulose
  • MK 458
  • Lactose
  • Fluorometholone
  • Indomethacin