Search for Polymorphic Phase Transformations in Chlorpropamide Form-A at High Pressures

Unusual seeding effect in the liquid-assisted high-pressure polymorphism of chlorpropamide

“…The role of kinetic factors known to influence crystallization at ambient conditions increases enormously at high pressure, when molecular motions are even more restricted, the sample is located in a confined space of a gasket hole, the pressuretransmitting fluid is not mixed and is often viscous, so that diffusion and convection processes are hindered. As a result of the kinetic control of nucleation and nuclei growth [28] , different phases can form, depending on the choice of the starting polymorph [29][30][31] , the hydrostatic medium [32][33][34][35][36][37] , or the compression/decompression protocol [26,[38][39][40][41][42] . An antidiabetic drug, chlorpropamide (4-chloro-N-(propylamino-carbonyl)benzenesulfonamide, C 10 H 13 ClN 2 O 3 S), is particularly prone to polymorphism [43,44] .…”

“…One could expect similarly high versatility in behavior on hydrostatic compression. To date, only the effect of pressure on the α-polymorph, which is the stable form at ambient pressure [45] , has been reported [34][35][36][37] . The α-polymorph undergoes at least one phase transition with increasing pressure in saturated ethanol solution (recrystallization is possible) [37] .…”

Polymorphism and Solvatomorphism 2009

“…Although no phase transformation of chlorpropamide Form-A was detected, nuclear magnetic resonance studied was used to study the molecular conformational changes that were induced by high pressure. 148 Raman spectroscopy and synchrotron X-ray diffraction of the 1:1 adduct between cyanuric acid and melamine were conducted in a diamond anvil cell, and the existence of a structural phase transition was found to take place around an applied pressure of 4.4 GPa. 149 The crystal structures of betaine monohydrate and (L)-cysteic acid monohydrate were found to be effectively unchanged even at pressures as high as 6.8 GPa, whereas crystals of (S)-4-sulfo-(L)-phenylalanine monohydrate were found to undergo a phase transition above 1 GPa that resulted in a reorientation of half the water molecules within their molecular layers and a change in molecular conformation of half of the (S)-4-sulfo-(L)-phenylalanine molecules.…”

Dynamics of an amorphous pharmacologically active compound – diazepam: a QENS study combined with molecular dynamics simulations

“…The results indicate the occurrence of reorientation jumps of the CH 3 group with a threefold barrier of height about 8 kJ mol À1 , 11 which is typical value for reorientation of methyl groups. [12][13][14][15] Later we focused on the amorphous sample, obtained by the melting and quench-cooling method and used NMR and atom-atom potential energy calculations to determine the distribution of energy barriers for the reorientation of methyl groups, nding that there is a distribution of energy barriers varying from $2 to $13 kJ mol À1 . 16 These calculations permitted also a separation of energy contributions coming from intra-and from inter-molecular interactions, with the former suggesting the possibility of a modication of the conformation of the diazepam molecule in the amorphous phase.…”