A strategy for producing predicted polymorphs: catemeric carbamazepine form V

A computationally assisted approach has enabled the first catemeric polymorph of carbamazepine (form V) to be selectively formed by templating the growth of carbamazepine from the vapour phase onto the surface of a crystal of dihydrocarbamazepine form II.     

Ability of the acetotoluides to form cyclodextrin inclusion complexes

Conclusion These series of experiments have shown that the -CD cavity was too small to allow stable inclusion complex formation. p-ACT is the isomer within this series that is best able to form inclusion complexes with -CD, then m-ACT and finally o-ACT. This would seem to indicate that the benzene ring of the molecule is the part of the structure most likely to penetrate the cavity since (a) -CD could not form stable complexes with any of the guest molecules and (b) less effective entry into the -CD cavity is the results of the acetamido group moving from p^–m^–o^– positions. Benzene ring penetration of the CD cavity is therefore required for stable inclusion complex formations in this group of compounds.     

Drug-polymer inclusion complex as a new pharmaceutical solid form

Drug-polymer crystalline inclusion complex is a new structure for the drug-polymer 2-component system, and also is a new drug solid form providing more options to optimize the drug pharmaceutical profile.     

Self-assembled monolayers: solidification of carbamazepine in Form II at an interface

A self-assembled monolayer incorporating well-spaced biphenyl moieties initiates solidification of carbamazepine at its interface. A detailed analysis of the resulting crystals using X-ray powder diffraction, FTIR-ATR as well as thermomicroscopy, indicates a preference for its crystallization in trigonal (Form II) polymorph.     

Solvent effects on glycine II. Water-assisted tautomerization

The water-assisted tautomerization of glycine has been investigated at the B3LYP/6-31+G** level using supermolecules containing up to six water molecules as well as considering a 1:1 glycine-water complex embedded in a continuum. The conformations of the tautomers in this mechanism do not display an intramolecular H bond, instead the functional groups are bridged by a water molecule. The replacement of the intramolecular H bond by the bridging water reduces the polarity of the N-H bond in the zwitterion and increases that of the O-H bond in the neutral, stabilizing the zwitterion. Both the charge transfer effects and electrostatic interactions stabilize the nonintramolecularly H-bonded zwitterion conformer over the intramolecularly hydrogen bonded one. The nonintramolecularly H-bonded neutral is favored only by charge transfer effects. Although there is no strong evidence whether the intramolecularly hydrogen bonded or non hydrogen bonded structures are favored in the bulk solution represented as a dielectric continuum, it is likely that the latter species are more stable. The free energy of activation of the water-assisted mechanism is higher than the intramolecular proton transfer channel. However, when the presumably higher conformational energy of the zwitterion reacting in the intramolecular mechanism is taken into account, both mechanisms are observed to compete. The various conformers of the neutral glycine may form via multiple proton transfer reactions through several water molecules instead of a conformational rearrangement.     

Vine-twining polymerization: amylose twines around polyethers to form amylose-polyether inclusion complexes

In this paper, we describe a new polymerization manner termed as "vine-twining polymerization" to produce amylose-polymer inclusion complexes. The polymerization was achieved by an enzymatic polymerization of alpha-D-glucose-1-phosphate monomer catalyzed by phosphorylase in the presence of polyTHF as a guest polymer. The structure of the product was determined by X-ray powder diffraction and (1)H NMR measurements to be the inclusion complex. The formation process of the inclusion complexes during the polymerization was also evaluated. Furthermore, the formation of the inclusion complexes by this polymerization method by using polyTHFs with various M(n)s and end groups, as well as other polyethers as the guest polymers, was examined.     

Pergolide mesyl­ate form II

A new polymorph of pergolide mesyl­ate or 8β‐[(methyl­sul­fan­yl)­methyl]‐6‐propyl­ergoline methane­sulfonate, C₁₉H₂₇N₂S⁺·CH₃SO₃⁻, is reported. Pergolide mesyl­ate form II crystallizes in the trigonal system, which is unique for ergot derivatives. Although the hydrogen‐bond system in form II differs completely from that in form I, the conformation of the pergolide moiety in various related structures is very similar.     

Solvent effect on the inclusion of 2-acetylnaphthalene by 1,1-di(p-hydroxyphenyl)cyclohexane

The effect of the solvents acetone (AT), dimethylsulfoxide (DMSO) and methylcellosolve (MCS) on the inclusion of 2-acetylnaphthalene (2-AN) in the host, 1,1-di(p-hydroxyphenyl)cyclohexane (DHC) has been investigated. Each solvent molecule is included in DHC in a molar ratio of 1.0, when DHC is crystallized from the solvents. The evaporation rate of these solvents from the host lattice decreases in the order AT, MCS and DMSO. The order agrees well with the interaction strength between the host and solvent molecule, which was measured by DSC and IR. 2-AN cannot be included in the crystals by crystallization from MCS and DMSO solutions. However, in AT solution both AT and 2-AN are included competitively and the morphology of the crystals is different from that obtained in pure solution. The amount of 2-AN in the crystals increases continuously with its concentration in solution. This behavior indicates that AT is replaced by 2-AN and the solid solution of the molecular complex is formed. The solid solution is a metastable form and the solution-mediated tranformation to the stable form (which includes only AT) was observed.     

Solvent Extraction of Pb(II) with AGDOMD

Abstract

The distribution of Pb(II) between an aqueous phase and a toluene phase containing dehydrated fatty acids found in distilled castor oil (AGDOMD) has been studied. Using the slope technique the conditional equilibrium constant of extraction was determined (kext = 1.02 × 10^?7) and the main species present in the organic phase was identified as (PbNO₃R. 2HR)_(o), where HR represents the fatty acid used.     

Solvent extraction of Cd(II) with isonitrosothiocamphor

The extraction coefficient of cadmium into 1,2-dichlorobenzene using isonitrosothiocamphor (HINTC) as a chelating agent at pH 8.5 is greater than 4585. It remains constant in the pH range of 7 to 10. The nature of the extracted species is ML₂ as derived by the slope ratio method. A careful analysis of the effect of different groups on the extraction coefficient and separation factors of a number of ions against Cd(II) has been carried out. The separation factors for most of the elements is characteristically high.     

Preparation and physicochemical characterization of carbamazepine (CBMZ): para-sulfonated calix[n]arene inclusion complexes

The formation of inclusion complexes with para-sulfonated calix[n]arene (PSC[n]A) was studied for carbamazepine (CBMZ), a poorly water soluble anticonvulsant drug. The effect of PSC[4]A and PSC[6]A on aqueous solubility of carbamazepine was studied extensively. The complete complexation of the drug was achieved after 48 h of shaking with PSC[n]A in water and evaporation of water to get solid complex. The interaction between PSC[n]A and CBMZ in solid state inclusion complexes was accomplished by aqueous phase solubility studies, HPLC, DSC, PXRD, FTIR, UV–Vis, and FT-Raman spectroscopy. The solubility of CBMZ increases as a function of PSC[n]A concentration. The results of the two phase solubility experiments are in good conformity to signify the formation of 1:1 (PSC[6]A:CBMZ) and 2:1 PSC[4]A:CBMZ complexes. The order of dissolution rate of CBMZ is inclusion complex > physical mixture > drug alone. The purpose of this study was to enhance solubility resulting in high dissolution rate and bioavailability of this essentially water insoluble drug.     

New inclusion compound — copper(II) hexacyanoferrate in faujasite

The copper(II) hexacyanoferrate lattice is formed within the zeolite when CuSO₄ reacts with hexacyanoferrate (II) encapsulated in faujasite under hydrothermal conditions. A quantity, of Cu²⁺ in excess of that necessary for ion exchange has an important role in forming the three dimensional structure, apparently through interactions with the zeolite skeleton. Formation of the hexacyanoferrate is accompanied by considerable deformation of the faujasite skeleton.L. V. Pisarzhevskii Institute of Physical Chemistry, Ukraine National Academy of Science, Ukraine, 252039 Kiev, Nauki Prospekt 31. Translated from Teoreticheskaya i Éksperimental'naya Khimiya, Vol. 32, No. 1, pp. 43–46, January–February, 1996. Original article submitted April 27, 1995.     

Determination of carbamazepine and its impurities iminostilbene and iminodibenzyl in solid dosage form by column high-performance liquid chromatography

An accurate and precise RP-HPLC method was developed and validated for the determination of carbamazepine and its impurities iminostilbene and iminodibenzyl in a tablet formulation with fluphenazine as an internal standard. Buffer-methanol (50 + 50, v/v) was used as the mobile phase. During validation, specificity, linearity, precision, accuracy, LOD, LOQ, and robustness of the method were tested. The method was proven to be specific against placebo interference. Linearity was evaluated over the concentration range of 100-500, 0.05-0.25, and 0.1-0.5 microg/mL, and the r values were 0.9994, 0.9997, and 0.9979 for carbamazepine, iminostilbene, and iminodibenzyl, respectively. Intraday precision of the method was good, and RSD was below 2% for all analytes. The accuracy of the method ranged from 100.69 to 102.10, 99.76 to 102.66, and 99.26 to 100.08% for carbamazepine, iminostilbene, and iminodibenzyl, respectively. LOD was 0.0125, 0.025, and 0.05 microg/mL and LOQ was 0.05, 0.05, and 0.1 microg/mL for carbamazepine, iminostilbene, and iminodibenzyl, respectiviely. Robustness of the method was proven by using a chemometric approach. The method was successfully applied to the analysis of commercially available carbamazepine tablets and showed good repeatability, with RSD below 2%.     

Solvent interactions with [Val(5)]angiotensin II in ethanol-water

Intermolecular NOE experiments have been used to explore the interactions of water and ethanol molecules in 35% ethanol/65% water (v/v) with the octapeptide hormone [val (5)]angiotensin II at temperatures from 0 to 25 degrees C. Magnetic dipole-dipole cross relaxation terms sigma(HH)(NOE) and sigma(HH)(ROE) for interaction of both solvent components suggest that ethanol molecules interact with the peptide backbone atoms strongly enough to associate for times comparable to the rotational correlation time of the peptide; comparison of observed ROE and NOE cross relaxation terms indicate that lifetimes of these interactions are of the order 0.4 ns at 5 degrees C. Formation of such peptide-ethanol complexes can also account for larger-than-expected values of the cross relaxation terms at higher temperatures. Alternative explanations of the observations reported are shown to be unlikely, primarily because they require unreasonable and highly localized concentrations of the ethanol near the peptide. Side chains of the peptide appear to experience no unusual interactions with ethanol. Cross relaxation terms for water-peptide backbone interactions indicate long-lived interactions of water with the backbone atoms although the nonpolar side chains of the peptide (Val3, Val5, Pro7, and possibly Phe8) do not interact in any specific way with water molecules. Cross relaxation terms for protons of the polar (Tyr4 and His6) side chains may reflect strong interactions with water, but analysis of these is confounded by solvent proton exchange and possible spin diffusion effects.     

The predictably elusive form II of aspirin

The elusive form II of aspirin has been obtained during co-crystallization experiments with levetiracetam or acetamide, and it has been characterized by IR, DSC, HPLC, and single-crystal X-ray diffraction.     

Solvent induced ionisation of η-allydicarbonylmolybdenum(II) complexes

[MoCl(η-C₃H₅)(CO)₂(MeCN)₂] dissolved in aprotic solvents is extensively ionised to [Mo(η-C₃H₅)(CO)₂(MeCN)₃]⁺[Mo₂Cl₃(η-C₃H₅)₂(CO)₄]^- with the liberation of free acetonitrile. The corresponding bromo- complex shows similar but less pronounced ionisation in (CD₃)₂CO, whereas the iodo-complex retains its molecular structure.     

Solvent extraction of copper(II) with chlorendic acid

The solvent extraction of Cu(II) with chlorendic acid has been studied The composition of the extracted species appears to be a function of pH. In the pH range 3.2-4.6, a monomeric species exists [Cu(II)(L(2-)], while at pH values greater than 4.5, a dimer in the form of [Cu(II)(L(2-)). H(2)L](2) and/or [Cu(II)(HL(-))(2)](2) is extracted.     

Solvent release upon ion association from entropy data. II

When a cation and an anion associate, the charge on the product is lower than that on the individual ions and solvent is released from their solvation shells to the bulk solvent. This release occurs when the associate is a solvent-shared or contact ion pair or an inner-type complex. The measurable molar entropy change involved is considered to be made up of four contributions: translational, rotational, electrostatic, and desolvation entropies. The former three can be calculated from the properties of the ions and solvents involved; hence, the fourth is obtained by difference. The release of solvent molecules from the crystalline frozen solvent to the liquid on melting is analogous to the solvent release from translational immobilization in the solvation shells of the ions. The molar entropy of melting of the solvent is used to estimate the amount of solvent released in the association process.     

Solvent effects in flow birefringence of polymer solutions. General theory and discussion of form effects

A new, more realistic optical model of a dilute polymer solution is used to calculate the intrinsic birefringence. A general formula is derived valid for an arbitrary equilibrium distribution function of particles in the system. Besides the contributions due to the polymer and solvent, the resulting relation for intrinsic birefringence also contains terms reflecting the effect of orientation of solvent surrounding the polymer chain and the contribution of optical interactions between polymer segments and molecules of solvent. A detailed discussion of the optical interactions in an isotropic solvent reveals that the problem may be transformed in the first approximation into that of interactions between excess dipoles; however, any separation of the macroform and microform effects has no theoretical justification. It is shown that the microform effect depends on a detailed optical model of the statistical segment, and this effect is calculated for two simple models. The expression suggested by Tsvetkov cannot be applied to a segment consisting of anisotropic monomers.