title: Effects of water content in physical mixture and heating temperature on crystallinity of troglitazone-PVP K30 solid dispersions prepared by closed melting method.
abstract: Troglitazone, which possesses two asymmetric carbons, is obtained as a mixture of four isomers present in equal amounts. Troglitazone (Lot T003) has two melting points, about 120 and 175 degrees C. To increase the bioavailability of insoluble troglitazone, troglitazone-polyvinylpyrrolidone K30 (PVP) solid dispersions (SDs) were prepared with water by a unique closed melting method. In this study, the effects of the water content in the physical mixture (PM) and the heating temperature on the apparent crystallinity of troglitazone in SDs prepared by this method were investigated. When the water content in the PM was controlled at 3%, although the apparent crystallinity of troglitazone in the SD prepared by heating at 105 degrees C did not decrease (99%), that of the SDs prepared by heating at 130 and 150 degrees C were reduced to 54 and 11%, respectively. This result indicated that the meltage of troglitazone varies depending on the heating temperature. The apparent crystallinity of troglitazone in the SDs decreased with increase in water content in the PM. In particular, SDs prepared by heating at 130 and 150 degrees C showed 0% apparent crystallinity when the water content in the PM were more than 13 and 8%, respectively. When the heating temperature used was higher than the glass transition temperature of PVP plasticized with water, troglitazone crystals were dissolved in the rubbery PVP. Therefore, even if the heating temperature is lower than the melting point of troglitazone during preparation, controlling the water content in the PM at a high level can produce a troglitazone SD with 0% apparent crystallinity.
authors.affiliation: Pharmaceutical Development Laboratories, Sankyo Co., Ltd., 1-12-1, Shinomiya, Hiratsuka, Kanagawa 254-0014, Japan. suhase@sankyo.co.jp
authors.forename: Susumu
authors.initials: S
authors.lastname: Hasegawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hamaura
authors.forename: Naho
authors.initials: N
authors.lastname: Furuyama
authors.forename: Akira
authors.initials: A
authors.lastname: Kusai
authors.forename: Etsuo
authors.initials: E
authors.lastname: Yonemochi
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Terada
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics; D002839:Chromans / Q000737:chemistry / Q000493:pharmacokinetics*; D003460:Crystallization; D006863:Hydrogen-Ion Concentration; D044367:Phase Transition; D011205:Povidone / Q000737:chemistry*; D012995:Solubility; D045162:Thiazolidinediones / Q000737:chemistry / Q000493:pharmacokinetics*; D044366:Transition Temperature; D000077288:Troglitazone; D014867:Water / Q000737:chemistry*; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D002839:Chromans; D045162:Thiazolidinediones; D014867:Water; D011205:Povidone; D000077288:Troglitazone