title: Studying the Impact of Modified Saccharides on the Molecular Dynamics and Crystallization Tendencies of Model API Nifedipine.
abstract: Molecular dynamics of pure nifedipine and its solid dispersions with modified carbohydrates as well as the crystallization kinetics of active pharmaceutical ingredient (API) above and below the glass transition temperature were studied in detail by means of broadband dielectric spectroscopy (BDS), differential scanning calorimetry (DSC), and X-ray diffraction method. It was found that the activation barrier of crystallization increases in molecular dispersions composed of acetylated disaccharides, whereas it slightly decreases in those consisting of modified monocarbohydrates for the experiments carried out above the glass transition temperature. As shown by molecular dynamics simulations it can be related to the strength, character, and structure of intermolecular interactions between API and saccharides, which vary dependently on the excipient. Long-term physical stability studies showed that, in solid dispersions consisting of acetylated maltose and acetylated sucrose, the crystallization of nifedipine is dramatically slowed down, although it is still observable for a low concentration of excipients. With increasing content of modified carbohydrates, the crystallization of API becomes completely suppressed. This is most likely due to additional barriers relating to the intermolecular interactions and diffusion of nifedipine that must be overcome to trigger the crystallization process.
authors.affiliation: †Department of Pharmacognosy and Phytochemistry, Medical University of Silesia in Katowice, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, ul. Jagiellonska 4, 41-200 Sosnowiec, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Kaminska
authors.affiliation: ‡Institute of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007 Katowice, Poland.|§Silesian Center of Education and Interdisciplinary Research, University of Silesia, ul. 75 Pulku Piechoty 1A, 41-500 Chorzow, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Tarnacka
authors.affiliation: ∥Institute of Non-Ferrous Metals, ul. Sowinskiego 5, 44-100 Gliwice, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Wlodarczyk
authors.affiliation: ‡Institute of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007 Katowice, Poland.|§Silesian Center of Education and Interdisciplinary Research, University of Silesia, ul. 75 Pulku Piechoty 1A, 41-500 Chorzow, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Jurkiewicz
authors.affiliation: ‡Institute of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007 Katowice, Poland.|§Silesian Center of Education and Interdisciplinary Research, University of Silesia, ul. 75 Pulku Piechoty 1A, 41-500 Chorzow, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Kolodziejczyk
authors.affiliation: ⊥Institute of Material Science, University of Silesia, 75 Pulku Piechoty 1a, 41-500 Chorzow, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Dulski
authors.affiliation: #Institute of Pharmacy, Center of Drug Absorption and Targeting, Felix-Hausdorff-Strasse 3a, 17489 Greifswald, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Haznar-Garbacz
authors.affiliation: ∥Institute of Non-Ferrous Metals, ul. Sowinskiego 5, 44-100 Gliwice, Poland.
authors.forename: L
authors.initials: L
authors.lastname: Hawelek
authors.affiliation: ‡Institute of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007 Katowice, Poland.|§Silesian Center of Education and Interdisciplinary Research, University of Silesia, ul. 75 Pulku Piechoty 1A, 41-500 Chorzow, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Kaminski
authors.affiliation: ∇Department of Animal Histology and Embryology, University of Silesia, ul. Bankowa 9, 40-007 Katowice, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Wlodarczyk
authors.affiliation: ‡Institute of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007 Katowice, Poland.|§Silesian Center of Education and Interdisciplinary Research, University of Silesia, ul. 75 Pulku Piechoty 1A, 41-500 Chorzow, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Paluch
mesh_terms: D002152:Calorimetry, Differential Scanning; D002241:Carbohydrates / Q000737:chemistry*; D003460:Crystallization / Q000379:methods*; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D009543:Nifedipine / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D044366:Transition Temperature; D014961:X-Ray Diffraction
chemical_list: D002241:Carbohydrates; D005079:Excipients; D009543:Nifedipine
keywords: acetylated saccharides; crystallization; glassy state; nifedipine; stabilization