Preparation and physical characterization of forms II and III of paracetamol

The polymorphic forms II and III of paracetamol were obtained by melting the marketed form I. Under the melting and cooling conditions used, it was possible to obtain forms I, II and III. The recrystallization conditions and the physical properties of forms II and III were investigated by means of various techniques: thermomicroscopy, DSC analysis, infrared microspectrometry and X-ray powder diffraction at room temperature and as a function of temperature. Form III was found to be very unstable. However, its formation seems to be an important intermediate step in the preparation of form II.     

Dynamics in the crystalline polymorphic forms I and II and form III of isotactic poly‐1‐butene

Following an earlier study of the ¹H relaxation and NMR line shapes, we have carried out selective one‐dimensional and two‐dimensional ¹³C solid‐state NMR studies that yield to detailed interpretation of the dynamics in form I, II, and III polymorphs of isotactic poly‐1‐butene. A specific defect diffusion along the side group is proposed to account for the temperature dependence of the ¹³C spectra in form I. The backbone of the helix in forms II and III is shown to undergo large angle motions above the glass‐transition temperature. High‐resolution solid‐state ¹³C two‐dimensional exchange NMR under magic‐angle spinning with cross‐polarization techniques demonstrates the existence of slow rotational jumps of the helices in form III with typical jump rates of about 10 s⁻¹. © 2000 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 38: 2611–2624, 2000     

Pressurization effects on the polymorphic forms of famotidine

The effects of high static pressure on the polymorphic modifications A and B of famotidine were examined by differential scanning calorimetry, infrared and Raman spectroscopy, and X-ray powder diffractometry. The obtained effects appeared to differ significantly depending on whether they were monitored by DSC or any of the other above techniques. In particular, DSC measurements tend to deceptively amplify a tendency of the pure modification B to turn into the more stable form A under pressurization, while the spectroscopic methods and XRPD exhibit no essential change in the crystal structure of the metastable form B. The apparent morphological transformation in the pressed samples stems from the nature of the DSC method itself.     

Thermodynamic properties of polymorphic forms of theophylline. Part I: DSC,TG, X-ray study

The physicochemical properties of theophylline hydrate and anhydrous polymorphic forms I and II were evaluated using crystallographic and calorimetric method. This study has been carried out with the following techniques: differential scanning calorimetry (DSC), thermogravimetric analysis (TG) and X-ray diffractometry. The X-ray patterns on powder for investigated compounds are presented.     

Determination of paracetamol in dosage forms by non-suppressed ion chromatography

An ion-chromatography procedure for the simultaneous determination of paracetamol and salicylic acid without suppression using UV detection is proposed. The method is applied to the determination of paracetamol in pharmaceuticals and also permits the quantitation of the total acetylsalicylic acid as salicylic acid.     

Assessment of processing and polymorphic form effect on the powder and tableting properties of microcrystalline celluloses I and II

Microcrystalline cellulose I (MCCI) is an excipient used as a diluent, disintegrant, glidant and binder for the production of pharmaceutical tablets. In this work, microcrystalline cellulose II (MCCII) was obtained from cotton fibers by basic treatment with 7.5 N NaOH followed by an acid hydrolysis. MCCI and MCCII materials were processed by wet granulation, dry granulation and spray drying. Either the polymorphic form or processing had no effects on the particle morphology or particle size. However, MCCII powders had a higher porosity, less packing tendency, degree of crystallinity, degree of polymerization and density, but a faster disintegration than MCCI. The tensile strength of MCCI was highly affected by the wet and dry granulation processes. Most of the resulting powder and tableting properties were dependent on the polymorphic form of cellulose, rather than on the processing employed.     

IR and Raman spectral and X-ray structural studies of polymorphic forms of sulfamethoxazole

The crystal structure of the polymorphic form III (hemihydrate) of sulfamethoxazole (SMZ) was determined to exist in both the E- and Z-forms by X-ray analysis and was compared with the polymorphic forms I and II which are known to exist in the E-form. IR spectra of I–III and their corresponding forms I_D–III_D which contain the deuterated amino and amido groups and D₂O and Raman spectra of I–III have been measured. For I–III, assignment of the stretching vibration [ν(NH) and ν(CH)] bands of amino and amido groups and the CH bond of the isoxazole ring involved in the inter-molecular hydrogen bonds has been proposed based on consideration of the IR and Raman spectra and the results of X-ray analysis. A relationship was established between the relative intensity and wavenumbers for the ν(CH) band in the inter-molecular C(sp²)H⋯X hydrogen bond of the E-form.     

Adhesion of high polymers. II. Wettability of elastomers

Data on wettability of elastomers should be considered basic to the understanding of all phases of elastomer adhesion. However, no such data in the form of critical surface tensions were available for elastomers other than polydimethylsiloxane. For this study, 18 elastomers were selected to determine the effects of functional groups, of geometrical and structural isomerisms, of copolymerization, and of the induced orientation upon wettability. Most results support the constitutive law of wettability established by Shafrin and Zisman. The effect of structural isomerisms in the form of a vinyl side group and cyclization is discussed. An equation for the calculation of critical surface tension of a copolymer or of a mixture of isomers is proposed as follows: where N_i is the mole-fraction of the individual monomer in the copolymer and \documentclass{article}\pagestyle{empty}\begin{document}$ \gamma _{c_i } $\end{document} is the critical surface tension of each homopolymer. Most elastomer adhesion studies conducted in the past were concerned with the diffusion theory of adhesion. This study further supports the conclusion on the role of diffusion and adsorption in adhesion advanced in Part I, especially with respect to the physical state of polymer at the time of application. The wettability data in this study could shed some light upon major basic mechanisms involved in elastomer reinforcement.     

Multinuclear solid state NMR investigation of two polymorphic forms of ciprofloxacin-saccharinate

Two polymorphic forms of a novel pharmaceutical compound, ciprofloxacin-saccharinate (CIP-SAC), are analyzed using one dimensional (1D) and two dimensional (2D) (1)H nuclear magnetic resonance (NMR) at fast magic angle spinning (MAS). Additionally (15)N spectroscopy and (1)H-(13)C correlation experiments were performed to complement our conclusions. The 1D (1)H NMR spectra of CIP and complexes reveal valuable information about the ionic bonding between ciprofloxacin and saccharine. Additionally, these spectra allow us to perform a clear characterization of each solid form, giving the number of molecules per unit cell in one of the polymorphs. From 2D (1)H-(1)H spectra obtained through double quantum correlations we can arrive at important conclusions about the hydrogen bonding, conformation, and intra and inter-molecular interactions present in these compounds. Comparing and contrasting the (1)H-(1)H correlation data obtained for both polymorphic forms and taking into account the single crystal structure data existing for the solid form CIP-SAC (II) was possible to extract some conclusions on the polymorph CIP-SAC (I) where no single crystal information is available. (1)H MAS NMR is shown to be an important tool in the field of polymorphism and for the characterization of multicomponent pharmaceutical compounds.     

Anisotropic surface energetics and wettability of macroscopic form I paracetamol crystals

Advancing (theta(A)) and receding (theta(R)) contact angles were measured with several probe liquids on the external facets (201), (001), (011), and (110) of macroscopic form I paracetamol crystals as well as the cleaved (internal) facet (010). For the external crystal facets, dispersive surface energies gamma(d) calculated from the contact angles were found to be similar (34 +/- 1 mJ/m(2)), while the polar components varied significantly. Cleaving the crystals exposed a more apolar (010) surface with very different surface properties, including gamma(d) = 45 +/- 1 mJ/m(2). The relative surface polarity (gamma(p)/gamma) of the facets in decreasing order was (001) > (011) > (201) > (110) > (010), which agreed with the fraction of exposed polar hydroxyl groups as determined from C and O 1s X-ray photoelectron spectroscopy (XPS) spectra, and could be correlated with the number of non-hydrogen-bonded hydroxyl groups per unit area present for each crystal facet, based on the known crystal structures. In conclusion, all facets of form I paracetamol crystals examined exhibited anisotropic wetting behavior and surface energetics that correlated to the presence of surface hydroxyl groups.     

Two novel polymorphic forms of iron‐chelating agent deferiprone

Thalassemia is a genetic blood disorder requiring life‐long blood transfusions. This process often results in iron overload and can be treated by an iron‐chelating agent, like deferiprone (3‐hydroxy‐1,2‐dimethylpyridin‐4‐one), C₇H₉NO₂, in an oral formulation. The first crystal structure of deferiprone, (Ia), was reported in 1988 [Nelson et al. (1988). Can. J. Chem. 66 , 123–131]. In the present study, two novel polymorphic forms, (Ib) and (Ic), of deferiprone were identified concomitantly with polymorph (Ia) during the crystallization experiments. Polymorph (Ia) was redetermined at low temperature for comparison of the structural features and lattice energy values with polymorphs (Ib) and (Ic). Polymorph (Ia) crystallized in the orthorhombic space group Pbca, whereas both polymorphs (Ib) and (Ic) crystallized in the monoclinic space group P2₁/c. The asymmetric units of (Ia) and (Ib) contain one deferiprone molecule, while polymorph (Ic) has three crystallographically independent molecules (A, B and C). All three polymorphs have similar hydrogen‐bonding features, such as an R₂²(10) dimer formed by O—H…O hydrogen bonds, an R₄³(20) tetramer formed by C—H…O hydrogen bonds and π–π interactions, but the polymorphs differ in their molecular arrangements in the solid state and are classified as packing polymorphs. O—H…O and C—H…O hydrogen bonds lead to the formation of two‐dimensional hydrogen‐bonded parallel sheets which are interlinked by π–π stacking interactions. In the three‐dimensional crystal packing, the deferiprone molecules were aggregated as corrugated sheets in polymorphs (Ia) and (Ic), whereas in polymorph (Ib), they were aggregated as a square‐grid network. The characteristic crystalline peaks of polymorphs (Ia), (Ib) and (Ic) were established through powder X‐ray diffraction analysis. The Rietveld analysis was also performed to estimate the contribution of the polymorphs to the bulk material.     

Two polymorphic forms of a mixed zinc/copper biquinoline dihydrogenphosphate

Two polymorphic forms of a mixed zinc/copper biquinoline dihydrogenphosphate are presented, showing almost identical monomeric units, viz. (2,2′‐biquinoline‐κ²N,N′)bis(dihydrogenphosphato‐κO)copper(II)/zinc(II), formulated as [Zn_xCu_1−x(H₂PO₄)₂(C₁₈H₁₂N₂)], with x = 0.88 (1) and 0.90 (2). The cation is tetrahedrally coordinated to a chelating biquinoline system and two diprotonated phosphate anions. The structures differ mainly in their intermolecular hydrogen‐bonding interactions, leading to different packing schemes. No significant evidence of stress due to the Zn/Cu solid solution formation was detected.     

Distinguishing between polymorphic forms of linezolid by solid-phase electronic and vibrational circular dichroism

For the first time two crystalline forms of the same compound (linezolid polymorphs) were investigated by means of the solid-phase ECD and VCD spectra. The ECD spectra show distinct differences and the band at 221 nm serves as a diagnostic one because it is present in form II but absent in form III. The VCD spectra strongly differ in the diagnostic carbonyl absorption range exhibiting two relatively strong bands of opposite signs.     

Voltammetric determination of paracetamol at NiO nanoparticles-modified carbon paste electrode in bulk and tablet dosage forms

Nickel oxide (NiO) nanoparticles were synthesized by a rapid method and well characterized. The nanoparticles were then used with graphite powder to prepare modified carbon paste electrode (CPE/NiO) for electrocatalytic oxidation of paracetamol (AC). The CPE/NiO showed higher electrocatalytic activity than nickel rod electrode in electrocatalytic oxidation of AC in alkaline media. The assay of AC, mechanism and kinetics of the electrooxidation process were investigated by cyclic voltammetry and chronoamperometry. The catalytic rate constant and the charge transfer coefficient of AC electrooxidation by the active nickel species and the diffusion coefficient of AC were also reported. The linear dependence of the peak current on the concentration of the AC was observed in the range 2–14 mM. This procedure was successfully applied to the determination of AC in tablets. The results showed sufficient precision, accuracy and achieved a mean recovery of 97.2% (RSD = 6.7%).     

In situ cryocrystallization of diphenyl ether: C-H...pi mediated polymorphic forms

Polymorphism in diphenyl ether has been identified during in situ crystallization via single-crystal X-ray diffraction. Only weak inter- and intramolecular C-H...pi interactions control the packing of the molecules in both crystal forms monoclinic centrosymmetric (P21/n) in form I and orthorhombic noncentrosymmetric (P212121) in form II.     

Sensitivity of fast-atom bombardment mass spectrometry to various polymorphic forms of cortisone acetate.

The present paper discusses non-traditional possibilities of the applications of mass spectrometry to the detection and study of differences in crystal polymorphic forms. The parameter of fast-atom bombardment which is sensitive to different polymorphs, namely the rate of the formation of cluster ions of an analyte with the glycerol matrix, was chosen for study. Using as an example the analysis of four different samples of cortisone acetate, varying in their polymorphic forms, treatment procedures, and dispersion of the crystalline powder, it is shown that the relative intensity of the cluster ion [MGH]+ (where M represents the analyte and G a molecule of glycerol) differs for two of the polymorphic forms and is the same for one of these forms, whether it is obtained by recrystallization from chloroform or by cryogrinding. Analysis of the time dependences of the [MGH]+ ion intensity allowed us to detect finer effects in the samples, associated with cryogrinding, namely differences in solubility and presumably, mechanoactivation.