title: The preparation, characterization, structure and dissolution analysis of apremilast solvatomorphs.
abstract: Apremilast (AP) {systematic name: (S)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-4-acetamidoisoindoline-1,3-dione} is an inhibitor of phosphodieasterase-4 (PDE4) and is indicated for the treatment of adult patients with active psoriatic arthritis. The ability of AP to form solvates has been investigated and three solvatomorphs of AP, namely, the AP ethyl acetate hemisolvate, C22H24N2O7S·0.5C4H8O2, the AP toluene hemisolvate, C22H24N2O7S·0.5C7H8, and the AP dichloromethane monosolvate, C22H24N2O7S·CH2Cl2, were obtained. The three AP solvatomorphs were characterized by X-ray powder diffraction, thermogravimetric analysis and differential scanning calorimetry. Single-crystal X-ray diffraction was used to analyze the structures, crystal symmetry, packing modes, stoichiometry and hydrogen-bonding interactions of the solvatomorphs. In addition, dissolution analyses were performed to study the dissolution rates of different AP solvatomorph tablets in vitro and to make comparisons with commercial apremilast tablets (produced by Celgene); all three solvatomorphs showed similar dissolution rates and similar values of the similarity factor f2in a comparison of their dissolution profiles.
authors.affiliation: SpringPharma Tech Co. Ltd, Weidi Road 9, 210046 Nanjing, People's Republic of China.
authors.forename: Yun Deng
authors.initials: YD
authors.lastname: Wu
authors.affiliation: Nanjing Luye Pharmaceutical Co. Ltd, Gaoxin Road 26, 210032 Nanjing, People's Republic of China.
authors.forename: Xiao Lei
authors.initials: XL
authors.lastname: Zhang
authors.affiliation: SpringPharma Tech Co. Ltd, Weidi Road 9, 210046 Nanjing, People's Republic of China.
authors.forename: Xiao Hong
authors.initials: XH
authors.lastname: Liu
authors.affiliation: SpringPharma Tech Co. Ltd, Weidi Road 9, 210046 Nanjing, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.affiliation: SpringPharma Tech Co. Ltd, Weidi Road 9, 210046 Nanjing, People's Republic of China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.affiliation: SpringPharma Tech Co. Ltd, Weidi Road 9, 210046 Nanjing, People's Republic of China.
authors.forename: Kun
authors.initials: K
authors.lastname: Shen
authors.affiliation: SpringPharma Tech Co. Ltd, Weidi Road 9, 210046 Nanjing, People's Republic of China.
authors.forename: Si Han
authors.initials: SH
authors.lastname: Zhang
authors.affiliation: SpringPharma Tech Co. Ltd, Weidi Road 9, 210046 Nanjing, People's Republic of China.
authors.forename: Yong Mei
authors.initials: YM
authors.lastname: He
authors.affiliation: SpringPharma Tech Co. Ltd, Weidi Road 9, 210046 Nanjing, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: SpringPharma Tech Co. Ltd, Weidi Road 9, 210046 Nanjing, People's Republic of China.
authors.forename: Ai Hua
authors.initials: AH
authors.lastname: Zhang
keywords: Otezla; PDE4; apremilast; crystal structure; hydrogen bonding; pharmaceutical compounds; psoriatic arthritis; solvatomorph