title: Effects of wet-granulation process parameters on the dissolution and physical stability of a solid dispersion.
abstract: This study investigated how the process parameters of wet-granulation affect the properties of solid dispersions (SDs), such as dissolution and physical stability. SDs of nilvadipine (NIL) and hypromellose prepared by spray-drying were wet-granulated and dried under various conditions. The NIL concentration at 4h and area under the curve from dissolution tests were taken to indicate dissolution. Then, the NIL crystallinity calculated from powder X-ray diffraction patterns of SD granules stored at 60°C for 3 months was evaluated to indicate physical stability. A statistical analysis revealed that the amount of granulation liquid (w/w%) and the ratio of water to ethanol in the liquid (v/v%) significantly affected the dissolution property, and that the drying temperature had a significant effect on the physical stability. Although exposure to water makes the wet-granulation process seem less suitable for granulating a SD, the results indicated that the process can be used to develop SD granules by selecting appropriate conditions, such as a lower proportion of granulation liquid, a higher water to ethanol ratio in the liquid, and a higher drying temperature.
authors.affiliation: Research Division, Chugai Pharmaceutical, Co., Ltd., 1-135, Komakado, Gotemba, Shizuoka 412-8513, Japan. Electronic address: kinoshita.ryo@chugai-pharm.co.jp.
authors.forename: Ryo
authors.initials: R
authors.lastname: Kinoshita
authors.affiliation: Pharmaceutical Technology Division, Chugai Pharmaceutical, Co., Ltd., 5-5-1, Ukima, Kita-ku, Tokyo 115-8543, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Ohta
authors.affiliation: Research Division, Chugai Pharmaceutical, Co., Ltd., 1-135, Komakado, Gotemba, Shizuoka 412-8513, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Shiraki
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Kenjirou
authors.initials: K
authors.lastname: Higashi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Moribe
mesh_terms: D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D065347:Hypromellose Derivatives; D008855:Microscopy, Electron, Scanning; D011208:Powders; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D011208:Powders; D065347:Hypromellose Derivatives
keywords: Amorphous drug; Nilvadipine; Solid dispersion; Solubility enhancement; Spray-drying; Wet-granulation