title: Evaluation of solid dispersions on a molecular level by the Raman mapping technique.
abstract: Troglitazone containing two asymmetric carbons has four isomers. Crystalline troglitazone consists of two crystalline diastereomer-pairs, RR/SS and RS/SR, which have different melting points. Using a closed melting method, troglitazone-polyvinylpyrrolidone solid dispersions with various crystallinities were prepared. Raman spectroscopy and its mapping technique were applied to discriminate between the crystalline RR/SS, crystalline RS/SR and amorphous form of troglitazone in solid dispersions. The results of the Raman mapping of solid dispersions showed the co-existence of crystal and amorphous forms, and which diastereomer-pairs remained as crystals, in addition to the distribution of the drug. Moreover, the distribution of PVP could be illustrated from the Raman mapping data. Thus, Raman spectroscopy and its mapping technique are useful tools to evaluate crystal and amorphous states, including discrimination of crystalline diastereomer-pairs in solid dispersions. In addition, by describing the distribution of the drug and the carrier, it could be guessed how drug crystals become amorphous during preparation from the point of view of the distribution of the amorphous form of the drug substance and the carrier.
authors.affiliation: Formulation Technology Research Laboratories, Daiichi Sankyo Co., Ltd., 1-12-1 Shinomiya, Hiratsuka, Kanagawa 254-0014, Japan. furuyama.naho.gh@daiichisankyo.co.jp
authors.forename: Naho
authors.initials: N
authors.lastname: Furuyama
authors.forename: Susumu
authors.initials: S
authors.lastname: Hasegawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hamaura
authors.forename: Shuichi
authors.initials: S
authors.lastname: Yada
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nakagami
authors.forename: Etsuo
authors.initials: E
authors.lastname: Yonemochi
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Terada
mesh_terms: D002626:Chemistry, Pharmaceutical; D002839:Chromans / Q000032:analysis* / Q000737:chemistry; D003460:Crystallization; D004304:Dosage Forms; D004337:Drug Carriers / Q000737:chemistry; D013059:Spectrum Analysis, Raman / Q000379:methods*; D013237:Stereoisomerism; D045162:Thiazolidinediones / Q000032:analysis* / Q000737:chemistry; D044366:Transition Temperature; D000077288:Troglitazone
chemical_list: D002839:Chromans; D004304:Dosage Forms; D004337:Drug Carriers; D045162:Thiazolidinediones; D000077288:Troglitazone