Preparation of stable aqueous suspension of a hydrophobic drug with polymers.
Pharmaceutical preparation of a hydrophobic aldose reductase inhibitor 5-(3-ethoxy-4-pentyloxyphenyl)-2,4-thiazolidinedione (CT112) was investigated. CT112 dissolved in a basic solution with different kinds of polymers was neutralized by acid to obtain a suspension preparation. In particular, the addition of a polymer, hydroxypropyl methyl cellulose (HPMC) provided a stable CT112 suspension with a homogeneous particle size, and there seemed to be an optimal concentration of HPMC for the stable suspension. The addition of polysorbate 80 brought higher CT112 solubility in water, but did not provide a stable suspension. X-ray diffraction, IR spectrum, and thermal analysis revealed that the particles in the suspension with HPMC had lower degree of crystallinity, less hydrophobic particle surface, and lower melting point and decreased fusion enthalpy than the suspension without HPMC. These results suggested that the highly stable CT112 suspension could be attained by the adsorption of the polymer.
Terayama
Hideo
H
Senju Pharmaceutical Co. Ltd., 2-5-8 Hiranomachi, Chuo-Ku, Osaka 541 0046, Japan. h-terayama@senju.co.jp
Inada
Katsuhiro
K
Nakayama
Hisayuki
H
Yasueda
Shinichi
S
Esumi
Kunio
K
D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry*; D004055:Differential Thermal Analysis; D004355:Drug Stability; D057927:Hydrophobic and Hydrophilic Interactions; D010316:Particle Size; D019999:Pharmaceutical Solutions; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D013055:Spectrophotometry, Infrared; D045162:Thiazolidinediones / Q000138:chemical synthesis* / Q000494:pharmacology; D014867:Water; D014961:X-Ray Diffraction
D019999:Pharmaceutical Solutions; D011108:Polymers; D045162:Thiazolidinediones; D014867:Water; C051003:risarestat; D002482:Cellulose; C008079:hydroxypropylcellulose