Preparation of rapidly disintegrating tablets containing itraconazole solid dispersions.
The disintegratability of tablets prepared from two types of solid dispersions containing the water-soluble polymer TC-5 and the enteric polymer HP-55 as an excipient were compared. The disintegratability was better in the tablets of solid dispersions containing non-water-soluble HP-55 than those containing TC-5. In consideration of the dissolubility of solid dispersions containing HP-55, the mean diameter of the solid dispersion (coating powder) must be controlled to 120 microm or less, but as this markedly increases the adhesion/aggregation tendency of the particles (angle of repose: 47 degrees ), control of the adhesion/aggregation tendency emerged as another problem. Therefore, surface-modification was performed in a high-speed agitating granulator using 0.1% light anhydrous silicic acid as a surface modifier, and marked improvement in the flowability was observed. This made continuous tableting using a rotary tablet machine possible even with the poorly flowable solid dispersions. Also, in tableting of the solid dispersions, no recrystallization of amorphous itraconazole by the tableting pressure was observed, and the tablets maintained satisfactory dissolubility. Moreover, it was possible to obtain the rapidly disintegrating tablets with very satisfactory properties, i.e., a tablet hardness of 30 N or higher and a disintegration time of 30 s or less, by the addition of croscarmellose as a disintegrant at 2% to the surface-modified solid dispersion and selection of the tableting pressure at 4.5 kN.
Oshima
Takao
T
Drug Formulation Department, Central Research Laboratories, Kaken Pharmaceutical Co., Ltd., Fujieda, Shizuoka, Japan. ohshima_takao@kaken.co.jp
Sonoda
Ryoichi
R
Ohkuma
Moriyuki
M
Sunada
Hisakazu
H
D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004224:Diterpenes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004355:Drug Stability; D005079:Excipients / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D017964:Itraconazole / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D008747:Methylcellulose / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics; D010316:Particle Size; D012995:Solubility; D013608:Tablets, Enteric-Coated / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D013696:Temperature; D014867:Water / Q000737:chemistry
D000935:Antifungal Agents; D004224:Diterpenes; D005079:Excipients; D013608:Tablets, Enteric-Coated; C415031:thyrsiflorin C; D014867:Water; D017964:Itraconazole; D008747:Methylcellulose; C053309:hydroxypropyl methylcellulose phthalate