Unexpected Single Crystal Growth Induced by a Wire and New Crystalline Structures of Lapatinib

Abstract

Single crystal growth of lapatinib free base was induced by immersion of a copper wire into a supersaturated methanolic aqueous solution yielding monoclinic anhydrous plates (space group P2 1 /c, Form 1) and needles of a previously unknown channel hydrate (in P4 2 2 1 2). Also, a new method has been developed herein to obtain anhydrous Form 1 via acid−base reaction of lapatinib ditosylate and sodium methoxide, avoiding the usage of an aqueous solution and hydrate formation. Anhydrous Form 2 as well as new solvates were produced via solution mediated transformation experiments, including a dichloromethane solvate with a powder X-ray diffraction pattern similar to that of anhydrous Form 2. Differential scanning calorimetry and solution equilibrium experiments helped to elucidate the interconversion pathways between Form 1, Form 2, and the solvates.

Local Structure of Ion Pair Interaction in Lapatinib Amorphous Dispersions characterized by Synchrotron X-Ray diffraction and Pair Distribution Function Analysis

“…This interaction is not expected in HPMC-E3, since there are no carboxylic groups to react with amines. On the other hand, lapatinib-lapatinib interactions are mainly driven by the N14−H–O3 hydrogen bond 29 which is related to the most basic nitrogen (pka 7.26), as can be inferred from the crystal structure ( Fig. 7 ).…”

“…2c ) shows a loss in the intermolecular order at r > 5 Å when in comparison to 3:1 LP:HPMCP, suggesting that the sample is predominantly amorphous with a possible presence of very low amount of crystalline domains. After 100 days both samples recrystallized into lapatinib free base Form 1 29 (as well as the pure phase semi-crystalline sample), indicating that the 3:1 drug:polymer ratio samples contained enough crystalline-like interactions to eventually trigger recrystallization. Since x-ray structure factors of the 1:3 and 1:1 LP-polymer ratios do not present Bragg peaks ( Fig.…”

“… 30 . Here, we assumed a molecular conformation corresponding to lapatinib in form 1 since amorphous samples generally crystallize into this polymorph and this is the stable form 29 . The XISF method calculates the intramolecular x-ray scattering based on the atomic x, y, z positions of the single input molecule using a zeroth order Bessel function based on a trust-region algorithim.…”

“…Grimwood, J.J. McKinnon, M.J. Turner, D. Jayatilaka, M.A. Spackman, University of Western Australia, 2012) based on crystallographic data of polymorph I 29 . Structure drawing and pKa calculation were performed using a Marvin 5.11.3 (Chemaxon, Budapest, Hungary) 2016 http://www.chemaxon.com .…”

Novel Process to Conductive Silver Nanowires Film via Simple Evaporative Crystallization of Silver Acetate/Polymer Solution on Substrates

“…Usually, the evaporative crystallization is dictated by two stages: nucleation (formation of seed crystal) and crystal growth. [ 34 ] Initially, as the solute concentration increases in a small area with evaporation, clusters with numerous solute molecules will be formed. The resulting clusters will act as crystalline seeds for crystal growth.…”