Effect of physical properties of troglitazone crystal on the molecular interaction with PVP during heating.
This study examined the effect of physical properties of troglitazone drug substance on the molecular interaction with polyvinylpyrrolidone K30 (PVP) during preparation by a closed melting method. Milling was conducted using impact and jet mills to change the physical properties of troglitazone, such as particle size, specific surface area, surface free energy and acidic-basic parameters. Solid dispersions (SDs) prepared from milled troglitazone, irrespective of milling method, showed almost 100% dissolution when not less than 7.5% of water was added during heating. SDs prepared from unmilled troglitazone showed almost 100% dissolution when not less than 12.8% of water was added during heating. Physical mixture (PM) containing unmilled troglitazone must be heated above at least 50 degrees C higher than the glass transition temperature (T(g)) of PVP to obtain an SD showing 100% dissolution, while PMs containing milled troglitazone could be heated above only 20 degrees C higher than the T(g) of PVP to obtain an SD showing 100% dissolution. The melting points of troglitazone in PMs containing milled troglitazone, irrespective of milling method, were lower than those in PMs containing unmilled troglitazone. These results indicated that specific interaction could occur more easily during heating between milled troglitazone and PVP during preparation by a closed melting method. In addition, Fourier transform infrared study indicated that hydrogen bonding could occur between the N-H of troglitazone and the C=O of PVP.
Hasegawa
Susumu
S
Pharmaceutical Development Laboratories, Sankyo Co. Ltd., 1-12-1 Shinomiya, Hiratsuka, Kanagawa 254-0014, Japan. suhase@sankyo.co.jp
Furuyama
Naho
N
Yada
Shuichi
S
Hamaura
Takeshi
T
Kusai
Akira
A
Yonemochi
Etsuo
E
Terada
Katsuhide
K
D002152:Calorimetry, Differential Scanning; D002839:Chromans / Q000737:chemistry* / Q000493:pharmacokinetics; D002849:Chromatography, Gas; D003461:Crystallography; D005079:Excipients / Q000737:chemistry*; D006358:Hot Temperature; D006860:Hydrogen Bonding; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D044367:Phase Transition; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics; D011205:Povidone / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013816:Thermodynamics; D045162:Thiazolidinediones / Q000737:chemistry* / Q000493:pharmacokinetics; D000267:Tissue Adhesions; D044366:Transition Temperature; D000077288:Troglitazone; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
D002839:Chromans; D005079:Excipients; D010975:Platelet Aggregation Inhibitors; D045162:Thiazolidinediones; D014867:Water; D011205:Povidone; D000077288:Troglitazone