title: Solvent-shift strategy to identify suitable polymers to inhibit humidity-induced solid-state crystallization of lacidipine amorphous solid dispersions.
abstract: The solvent-shift strategy was used to identify appropriate polymers that inhibit humidity-induced solid-state crystallization of amorphous solid dispersions (ASDs). Lacidipine with the polymers, PVP-K30, HPMC-E5 or Soluplus, were combined to form amorphous solid dispersions prepared by solvent evaporation. The formulations were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier-transform infrared spectroscopy (FT-IR) and were subjected to in vitro dissolution testing. The moisture had a significant impact on the amount dissolved for the solid dispersions. Molecular docking studies established that hydrogen bonding was critical for the stabilization of the solid dispersions. The rank order of the binding energy of the drug-polymer association was Soluplus (-6.21 kcal/mol)>HPMC-E5 (-3.21 kcal/mol)>PVP-K30 (-2.31 kcal/mol). PVP-K30 had the highest water uptake among the polymers, as did ASD system of lacidipine-PVP-K30 ASDs. In the Soluplus ASDs, with its strong drug-polymer interactions and low water uptake, moisture-induced solid-state crystallization was not observed.
authors: School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China.
authors: Mengchi
authors: M
authors: Sun
authors: Department of Pharmacy, Tianjin Medical University Cancer Institute and Hospital, China.
authors: Chunnuan
authors: C
authors: Wu
authors: School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China.
authors: Qiang
authors: Q
authors: Fu
authors: School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China.
authors: Donghua
authors: D
authors: Di
authors: School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China.
authors: Xiao
authors: X
authors: Kuang
authors: School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Wenhua Road, No.103, Shenyang 110016, China.
authors: Chao
authors: C
authors: Wang
authors: School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China.
authors: Zhonggui
authors: Z
authors: He
authors: Key Laboratory of Structure-Based Drug Design and Discovery, Shenyang Pharmaceutical University, Ministry of Education, Wenhua Road, No. 103, Shenyang 110016, China. Electronic address: jianwang@syphu.edu.
authors: Jian
authors: J
authors: Wang
authors: School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, No. 103, Shenyang 110016, China; Municipal Key Laboratory of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, China. Electronic address: sunjin66@21cn.com.
authors: Jin
authors: J
authors: Sun
mesh_terms: D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004095:Dihydropyridines / Q000737:chemistry*; D006813:Humidity; D065347:Hypromellose Derivatives / Q000737:chemistry*; D062105:Molecular Docking Simulation; D011092:Polyethylene Glycols / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry*; D033362:Powder Diffraction; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D004095:Dihydropyridines; D011145:Polyvinyls; D012997:Solvents; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D014867:Water; C060285:lacidipine; D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols; D011205:Povidone
keywords: Drug–polymer interactions; Humidity-induced solid-state crystallization; Molecular docking; The solvent-shift strategy; Water uptake