Powder X-ray Diffractometry Patterns Research Articles

Characterization of two polymorphs of lornoxicam

The aim of the study was to prepare and to characterize two polymorphs of lornoxicam, a water-insoluble non-steroidal anti-inflammatory drug, which has thus far received no exploration of its polymorphs. Form I and form II of lornoxicam were prepared by recrystallization and characterized by X-ray powder diffractometry (XRPD), thermal analysis, Fourier transform infrared spectroscopy and scanning electron microscopy. The solubility and dissolution of both polymorphs were also determined and compared to provide the basis for polymorph selection in formulation. The crystal structures of the two polymorphs were established by the experimental XRPD patterns. Form I was demonstrated to be triclinic with two kinds of intermolecular hydrogen bonds, while form II was orthorhombic with two kinds of intramolecular hydrogen bonds. The morphologies of form I and form II were observed to be rectangle and approximately oval, respectively. Form II had the significantly higher solubility and dissolution and would be the suitable polymorph for the preparation of oral and injectable dosage forms of lornoxicam.

Solid state of aceclofenac: characterization, transformation

The objective of this work was to investigate the existence of polymorphs and pseudopolymorphs of aceclofenac which is a peripherally acting, non-steroidal anti-inflammatory analgesic with anti-inflammatory, antiarthritic and antipyretic activities. Three crystal forms of aceclofenac have been isolated by recrystallization and characterized by differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD) and thermogravimetric analysis. The DSC and PXRD patterns of the three crystal forms of aceclofenac were different respectively. After storage of 1 month at 0 % RH (silica gel, 20 °C), 52 % RH (saturated solution of Na2Cr2O7·2H2O/20 °C) and 95 % RH (saturated solution of Na2HPO4/20 °C), Form 1 and Form 3 (from methylethyl ketone) were not transformed, but Form 2 (from DMSO) was transformed to Form 1 at 95 % RH.

Solid state of a new PDE-5 inhibitor DA-8159: Characterization, dissolution, transformation

The polymorphic forms of a new PDE-5 inhibitor DA-8159 were prepared and characterized by differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD) and thermogravimetric analysis (TG). Two crystal forms and one amorphous form of DA-8159 have been isolated by recrystallization and characterized by DSC, TG and PXRD. From the TG data it was confirmed that two crystal forms are neither solvates nor hydrates. The PXRD patterns of the two crystal forms were different. In the dissolution studies in simulated intestinal fluid at 37 ± 0.5°C, the solubility decreased in the order of amorphous form > Form 1 > Form 2. After storage of 60 days, Form 1 was transformed to Form 2. Form 2 was not transformed. The amorphous form was transformed to Form 2 at 52% R.H. and 95% R.H., but it did not transform at 0% R.H.

Physical Stabilizing Effect of Biopolymers on Solid Dispersions Containing Indomethacin and Polyethylene Glycol

Solid dispersions of poorly water-soluble drug, indomethacin (IMC), and carriers at a ratio of 1:9 were prepared by melting method. The carriers used in this study were polyethylene glycol 4000 (PEG4000), hydroxypropyl methylcellulose (HPMC) and pectin. The solid dispersions obtained were characterized by powder x-ray diffractometry (PXRD) and dissolution studies. PXRD patterns showed that all solid dispersions led to amorphous products while their physical mixture still showed the crystalline state of drug. Crystalline drug was clearly detectable in solid dispersion products containing only IMC and PEG4000 after storage for 2 months. The formulations with biopolymer (i.e., HPMC, pectin or their combination) showed no drug crystal after storage. More than 80% of IMC dissolved within 5 minutes for all formulations after preparation while less than 40% of IMC dissolved, within 5 minutes, from the formulations containing IMC, PEG4000 and HPMC after storage for 2 months. The slower drug dissolution may be due to the gel-forming properties of HPMC as well as the agglomeration of the products after storage. The results suggested that either HPMC or pectin in solid dispersions can help to prevent the crystallization of amorphous IMC in solid dispersion, probably by a polymer anti-plasticizing effect. Pectin showed superior stabilizing effect with no retardation effect on drug dissolution.

Solid state of CG-400549, a novel FabI inhibitor: Characterization, dissolution, transformation

The polymorphic and pseudopolymorphic forms of CG-400549, a novel FabI inhibitor with potent in vivo activity were prepared and characterized by differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD) and thermogravimetric analysis (TG). Seven crystal forms of CG-400549, one anhydrate and six solvates, have been isolated by recrystallization and the DSC and PXRD patterns of the seven crystal forms of CG-400549 were different respectively. The dissolution patterns of these seven crystal forms of CG-400549 were studied and they showed significant differences in the dissolution rate. After storage of 1 month at 0% RH (silica gel, 20°C), 52% RH (saturated solution of Na(2)Cr(2)O(7)2H(2)O/20°C) and 95% RH (saturated solution of Na(2)HPO(4)/20°C), all crystal forms were not transformed.

Solid State of Tulobuterol : Characterization, Dissolution, Transformation

The objective of this work was to investigate the existence of new crystal forms of tulobuterol which is used to prevent morning asthma attacks by agonist and the transformation of crystal forms. Three crystal forms of tulobuterol have been isolated by recrystallization and Form 2 was transformed to Form 4 at 52% RH and 95% RH and these four crystal forms are characterized by differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD) and thermogravimetric analysis (TG). The DSC and PXRD patterns of four crystal forms of tulobuterol were different respectively. The dissolution patterns of these three crystal forms of tulobuterol were studied and they showed significant differences in the dissolution rate. After storage of 2 months at 0% RH (silica gel, ), 52% RH (saturated solution of ) and 95% RH (saturated solution of ), Form 1 and Form 3 were not transformed. But Form 2 was transformed to Form 4 at 52% RH and 95% RH.

Thermal and structural properties of ball milled Co50Ni50powders

Nanostructured Co 50 Ni 50 powders were mechanically alloyed from elemental Co and Ni powders using a planetary ball mill type Fritsch P7 under argon atmosphere. The milled powders were characterized by scanning electron microscopy, X-ray powder diffractometry (XRD) and differential scanning calorimetry (DSC). The SEM micrographs show a progressive refinement of the particles size with milling time. For longer milling time, the particles morphology is homogenous indicating the formation of the alloy. The XRD reveals the interdiffusion of the Ni and Co elements as milling proceeds and the formation of an heterogeneous solid solutions with two structures: fcc-Ni(Co) and fcc-Co(Ni), having different structural and microstructural parameters. The XRD patterns refinement reveals also the Co allotropic transformation from the hcp to fcc structure form at the early stage of milling. DSC results show a broad exothermic reaction indicating a strain relaxation and a recovery process.

Crystal forms of naproxen

The objective of this work was to investigate the existence of polymorphs and pseudopolymorphs of naproxen and the transformation of crystal forms. Four crystal forms of naproxen have been isolated by recrystallization and characterized by differential scanning calorimetry, powder X-ray diffractometry and thermogravimetric analysis. The differential scanning calorimetry and powder X-ray diffractometry patterns of the four crystal forms were different respectively. In the dissolution studies in pH 6.8 ± 0.05 buffer equilibrated at 37 ± 0.5°C, the solubility of four crystal forms was similar (within the error range). After storage of 1 month at 0% RH (silica gel, 20°C), 52% RH (saturated solution of Na(2)Cr(2)O(7.2)H(2)O/20°C) and 95% RH (saturated solution of Na(2)HPO(4)/20°C), Form 2 and Form 4 were transformed to Form 1, but Form 3 and Form 1 were not transformed and they were shown to have a good physical stability at room temperature for 1 month.

Crystal forms of SK-3530

The objective of this work was to investigate the existence of polymorphs of SK-3530 and the transformation of crystal forms. Two crystal forms of SK-3530 have been isolated by recrystallization and characterized by differential scanning calorimetry, powder X-ray diffractometry and thermogravimetric analysis. The differential scanning calorimetry and powder X-ray diffractometry patterns of two crystal forms were different respectively. After storage of 1 month at 0% RH (silica gel, 20°C), 52% RH (saturated solution of Na(2)Cr(2)O(7)·2H(2)O/20°C) and 95% RH (saturated solution of Na(2)HPO(4)/20°C), Form 2 was not transformed to Form 1 and two forms were shown to have a good physical stability at room temperature for 1 month. In the dissolution studies in pH 6.8 buffer at 37 ± 0.5°C, the dissolution rate of Form 2 was significantly higher than that of Form 1 under 30 min.

Effect of position isomerism on the formation and physicochemical properties of pharmaceutical co-crystals

The effect of position isomerism on the co-crystals formation and physicochemical properties was evaluated. Piracetam was used as the model compound. Six position isomers, 2,3-, 2,4-, 2,5-, 2,6-, 3,4-, and 3,5-dihydroxybenzoic acid (DHBA), were used as the co-crystal formers. Co-crystals were prepared on a 1:1 molar ratio by crystallization from acetonitrile. The solid-state properties of co-crystals were characterized using X-ray powder diffractometry (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR). All co-crystal formers formed co-crystal with piracetam except 2,6-DHBA. This failure was possibly due to steric hindrance of two bulk hydroxyl groups and preference of intra-molecular hydrogen bonding formation between hydroxyl group and carboxylic acid group. The XRD patterns of resulting co-crystal indicated that they are highly crystalline and different than parental compounds. Based on the single crystal data, P_23DHBA is orthorhombic while P_24DHBA, P_34DHBA, and P_35DHB belong to monoclinlic system. The hydrogen bonding network patterns of the co-crystals are also different. DSC data showed that the melting temperatures of resulting co-crystals are all lower than that of the starting materials. The melting point rank order of the co-crystals is: P_24DHBA > P_34DHBA > P_23DHBA > P_25DHBA > P_35DHBA. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:246–254, 2010

Crystal forms of atorvastatin

The objective of this work was to investigate the existence of new polymorphs and pseudopolymorphs of atorvastatin and the transformation of crystal forms. Three crystal forms of atorvastatin have been isolated by recrystallization and characterized by powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TG). The PXRD and DSC patterns of the three crystal forms were different respectively and it was confirmed that Form 3 is a new crystal form. After storage of 2 years at room temperature, this new crystal form was not transformed and it was shown to have a good physical stability.

Physicochemical characterization and dissolution properties of binary systems of pyrimethamine and 2- hydroxypropyl-&#946-cyclodextrin

Pyrimethamine (PYR), a drug effective against protozoan parasites, such as Toxoplasma gondii and Plasmodium falciparum, is poorly water soluble and exhibits marked variation in oral bioavailability. This study was aimed at investigating the possibility and extent of enhancement of the dissolution properties of PYR via complexation with 2-hydroxypropyl-
-cyclodextrin (HP-
-CD) as well as characterization of the complex formation of the drug with the cyclodextrin. The interaction between PYR and HP-
-CD in solution was studied by phase solubility analysis while binary systems of the compounds at 1:1 molar ratios were prepared by using the physical mixture, kneading, co-evaporation and freeze-drying methods. The binary systems were characterized using differential scanning calorimetry (DSC), powder x-ray diffractometry (PXRD) and Fourier transform infrared (FT-IR) spectroscopy. Phase solubility studies revealed an AL-type diagram indicating a 1:1 stoichiometric inclusion complex and a stability constant value of 914 M-1. Solubility and dissolution rates of PYR and the binary systems were determined and found to be markedly enhanced by cyclodextrin complexation. The extent of enhancement of dissolution properties was dependent on the preparation method of the complex, and the product prepared by the freeze-drying method was shown to have the most superior dissolution efficiency than the other binary systems. The PXRD patterns and DSC curves especially for the co-evaporated and freeze-dried systems indicated strong drug amorphization and/or inclusion of PYR in the CD cavities. The results of this study suggest that the complexation of PYR with HP-
-CD could reduce variability in the drug absorption and improve therapeutic efficacy of the drug through increased drug dissolution efficiency.

The effect of physical state on the drug dissolution rate

In this work, the enhancement of drug dissolution rate through the preparation of new formulations containing Nimodipine in molecular level dispersion or in nanodispersion into poly(vinyl pyrrolidone) (PVP) matrix, was investigated. Differential scanning calorimetry (DSC) and modulated-temperature differential scanning calorimetry (MTDSC) in combination with X-ray powder diffractometry (XRPD) and scanning electron microscopy (SEM) studies showed that Nimodipine was amorphous in solid dispersions of 10 or 20 mass%, and mainly dispersed on a molecular level. This behaviour is attributed to the strong interactions taking place between the amine group of Nimodipine and carbonyl group of PVP. At higher drug loadings, crystal reflections in XRPD patterns and melting peaks of Nimodipine in DSC traces, indicated presence of drug in crystalline form. Micro-Raman studies in combination with SEM micrographs showed that the mean particle size increases with drug content in the formulations, up to 10 μm. Moreover, both XRPD patterns and micro-Raman spectra seem to indicate that Nimodipine crystallized in a second, thermodynamically stable, crystal modification II. The physicochemical characteristics of Nimodipine and the particle size distribution directly affect the dissolution rate enhancement, which is higher in amorphous dispersions.

Solid State Interconversion Between Anhydrous Norfloxacin and Its Hydrates

This work is focused on characterizing and evaluating the solid state interconversion of norfloxacin (NF) hydrates. Four stoichiometric NF hydrates, dihydrate, hemipentahydrate, trihydrate, pentahydrate and a disordered NF state, were generated by various methods and characterized by X-ray powder diffractometry (XRPD), thermal analysis and Karl Fisher titrimetry. XRPD patterns of all NF hydrates exhibited crystalline structures. NF hydrate conversion was studied with respect to mild elevated temperature and various degrees of moisture levels. NF hydrates transformed to anhydrous NF Form A after gentle heating at 60 degrees C for 48 h except dihydrate and trihydrate where mixture in XRPD patterns between anhydrous NF Form A and former structures existed. Desiccation of NF hydrates at 0% RH for 7 days resulted in only partial removal of water molecules from the hydrated structures. The hydrated transitional phase and the disordered NF state were obtained from the incomplete dehydration of NF hydrates after thermal treatment and pentahydrate NF after desiccation, respectively. Anhydrous NF Form A and NF hydrates transformed to pentahydrate NF when exposed to high moisture environment except dihydrate. In conclusion, surrounding moisture levels, temperatures and the duration of exposure strongly influenced the interconversion pathways and stoichiometry of anhydrous NF and its hydrates.

Crystalline Form Information from Multiwell Plate Salt Screening by Use of Raman Microscopy

The purpose of this study was to establish a useful methodology, possibly providing information on the stoichiometry of pharmaceutical drug salts obtained from salt screening by using a multiwell plate and a Raman microscope. Tamoxifen salt screening was conducted with monobasic and polybasic acids on 96-well quartz plates with a Raman microscope. Appearance and crystalline forms of salts prepared on 96-well plates were observed by polarizing light microscope and Raman microscope, respectively. Based on the results of the salt screening, tamoxifen citrate and fumarate salts were prepared on a large scale. The salts prepared were characterized by powder X-ray diffractometry (PXRD) and ion chromatography. The results of the multiwell salt screening indicated that tamoxifen has a tendency toward the formation of mono salt as opposed to hemi salt with polybasic acid, and that most of tamoxifen salts gave several potential polymorphic forms. PXRD patterns of scaled-up tamoxifen citrate and fumarate salts suggested that the same crystalline form was obtained from the binary mixture regardless of molar ratios of 2:1 or 1:1 (tamoxifen/acid). The crystalline forms obtained were tamoxifen monocitrate and monofumarate salts as measured by ion chromatography. Salt screening on multiwell plates with a Raman microscope provided novel insight into the characteristics prediction of the stoichiometrical salts in addition to potential polymorph information. Based on the stoichiometrical information of salts, the amount of compound and time required for crystalline form selection of drug candidates would be significantly reduced.

Preparation and Crystal Characterization of a Polymorph, a Monohydrate, and an Ethyl Acetate Solvate of the Antifungal Fluconazole

The preparation and solid-state characterization of three crystalline modifications of the antifungal agent fluconazole [2-(2,4-difluorophenyl)-1,3-bis-(1H-124-triazol-1-yl)-propan-2-ol] are reported. Recrystallization of fluconazole from propan-2-ol yielded a polymorph (Form III), whereas the solvents water and ethyl acetate yielded the solvated products fluconazole monohydrate and fluconazole·(ethyl acetate)0.25, respectively. These species were analyzed by thermogravimetry (TGA), differential scanning calorimetry (DSC), FTIR spectroscopy, powder X-ray diffractometry (PXRD), and single crystal X-ray diffraction. Availability of the hitherto unknown crystal structures facilitated interpretation of the thermal data and clarified previous findings relating to the polymorphism of this compound. Fluconazole was found to exist as a centrosymmetric hydrogen bonded dimer in Form III. For the solvated phases, the solvent locations within the drug host matrices were established as isolated sites for water molecules and constricted channels for ethyl acetate molecules. Desolvation of the monohydrate and ethyl acetate solvate yielded polymorphic Form I. Reference PXRD patterns computed from the refined single-crystal X-ray data for the title compounds are presented. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association

Solid-State Variation of Troglitazone Drug Substance by Using a Different Recrystallization Method

Rapid and slow crystallization methods (A and B) were applied for troglitazone, an equal mixture of four stereoisomers. Differences in the powder x-ray diffractometry patterns and hygroscopic patterns were observed among the samples crystallized by these methods, suggesting that troglitazone has solid-state variation. In this article, troglitazone recrystallized by method A was evaluated to clarify its structural characteristics and physical property. The crystal structure of predried troglitazone recrystallized by method A was proved to be a dihydrate. By drying, it changed reversibly to an anhydrate, which is the same structure as the RS/SR form, keeping the same enantiomer ratio. The solubility of the troglitazone by method A higher than that by method B at all enantiomer levels. But making the troglitazone amorphous equalized the enantiomeric solubilities of the substances by both methods as well as increased the intrinsic solubilities. Troglitazone by both methods was proved to be stable and retained the ratio of the stereoisomers.

Synthesis of Nanocrystalline Chromium Nitride Powders by Direct Nitridation of Chromium Oxide.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of Nanocrystalline Chromium Nitride Powders by Direct Nitridation of Chromium Oxide

Nanocrystalline CrN powder was synthesized by the direct nitridation of nanosized Cr2O3 powder. Powder X‐ray diffractometry patterns indicated that pure cubic‐phase CrN powder could be obtained by nitridation at 800°C for 8 h. Transmission electron microscopy images showed that the particle sizes were 40–80 nm. The effect of the nitridation temperature and holding time on the powder properties was studied.

Neotame anhydrate polymorphs I: preparation and characterization.

To prepare, characterize, and compare polymorphs of neotame anhydrate. Neotame anhydrate polymorphs were prepared from amorphous or crystalline anhydrate by crystallization or suspension in various organic solvents, or by dehydration of neotame monohydrate. The following techniques were used for characterization: differential scanning calorimetry, thermogravimetry, hot-stage microscopy, powder X-ray diffractometry (PXRD), 13C solid-state nuclear magnetic resonance (SSNMR) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy, dynamic water vapor sorption/desorption, and density measurements. Seven polymorphs (Forms A-G) of neotame anhydrate were prepared and show different thermal properties and PXRD patterns. Two enantiotropically related pairs were identified: B and C; E and A. 13C SSNMR and FTIR spectroscopy clearly distinguish between Forms A, D, F, and G, which show similar needle-shaped morphology but distinct differences in dynamic water vapor sorption/desorption and density. The 13C SSNMR chemical shifts suggest conformational polymorphism. The stability in the presence of water vapor follows the rank order, G > A > D approximately = F, which resembles the rank orders of the molar volume and of the polarity of the solvents from which they crystallized. The neotame anhydrate polymorphs appear to show different molecular conformations. The less dense polymorphic structures crystallize from solvents of greater polarity and sorb water vapor less rapidly and less completely. Two enantiotropic pairs were discerned.