Hideo Terayama

AQUEOUS DISPERSION BEHAVIOR OF DRUG PARTICLES BY ADDITION OF SURFACTANT AND POLYMER

The effect of surfactant and polymer on dispersion stability of aqueous suspensions of 5-(3-ethoxy-4-pentyloxyphenyl)-2,4-thiazolidinedione (CT112) was investigated by measuring the adsorbed amount of surfactant and polymer, zeta potential, particle size, and sedimentation rate of CT112. The addition of celluloses rather than sodium dodecyl sulfate (SDS) provided a high stable suspension of CT112. In addition, mixed systems of celluloses and SDS enhanced CT112 dispersion more effectively. The mechanism of dispersion stability of CT112 by addition of SDS and celluloses is discussed.

Evaluation of ophthalmic suspensions using surface tension

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.

Effect of dilution on aqueous dispersion of drug particles

Aqueous suspensions of 5-(3-ethoxy-4-pentyloxyphenyl)-2,4- thiazolidinedione (CT112) have been prepared by neutralization of alkaline solutions of CT112 in the presence of surfactant/polymer with HCl. Sodium dodecyl sulfate (SDS) and celluloses have been used. The effect of dilution of water on the aqueous CT112 dispersion has been studied by measuring the amount adsorbed of surfactant and polymer, ζ-potential, particle size, and sedimentation behavior. The dispersion stability of aqueous CT112 suspension in the presence of polymer or SDS by dilution of water depends on the initial concentration of polymer or SDS. On the other hand, the dispersion stability of aqueous CT112 suspension in the presence of both polymer and SDS is stable even by dilution of water. The mechanism for the effect of dilution of water has been discussed.

Kinetics of formation of drug particles in the presence of surfactant/polymer

Aqueous suspensions of 5-(3-ethoxy-4-pentyloxyphenyl)-2,4-thiazolidinedione (CT112) were prepared by neutralization of alkaline solutions of CT112 in the presence of surfactant and polymer. The formation of CT112 particles was kinetically studied by measuring the change of backscattering percent of the suspensions with time after neutralization. The rate of particle formation in the presence of sodium dodecyl sulfate (SDS) was much faster than those in the presence of celluloses while the particle size obtained in the presence of SDS was much smaller than those in the presence of celluloses. In the presence of both SDS and celluloses, stable aqueous dispersions of CT112 were obtained. The mechanisms of particle formation of CT112 as well as dispersion stability were also discussed.

AQUEOUS DISPERSION OF STEROIDS BY ADDING CELLULOSES

Abstract The aqueous dispersion of steroids by adding celluloses was studied by measuring adsorbed amount and dispersion stability. The adsorbed amount of celluloses was greater for a steroid with a higher critical surface tension, resulting in a higher dispersion stability. ESR studies using spin-labeled celluloses show that the cellulose adsorbed on the steroid showing a high dispersion stability takes mainly a conformation of tails or loops.