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Nuclear magnetic resonance (NMR) longitudinal rotating frame relaxation time (T 1ρ ), rarely used in low-field NMR, can be more effective than conventional T 1 and T 2 relaxation times to differentiate polymorphic forms of solid pharmaceuticals. This could be attributed to T 1ρ sensibility to structural and molecular dynamics that can be enhanced by changing the strength of the oscillating magnetic field ( B 1 ) of spinlock pulses. Here, we compared the capacity of T 1 , T 2 , and T 1ρ to differentiate inactive (A) and active (C) crystalline forms of the World Health Organization essential drug Mebendazole. The results showed that T 1 and T 2 values of both forms were statistically identical at 0.47 T. Conversely, T 1ρ of both forms measured with weak spinlock B 1 fields, ranging from 0.08 to 0.80 mT were statistically different in the same spectrometer. The T 1ρ also has the limit of detection to detect the presence of at least 10% of inactive A form in the active C form. Therefore, T 1ρ , measured with weak spinlock B 1 fields can be an effective, streamlined, and complementary approach for characterizing not only solid active pharmaceutical ingredients but other solid-state materials as well.

In the pharmaceutical industry, the unexpected appearance of crystalline forms could impact the therapeutic efficacy of an Active Pharmaceutical Ingredient (API). For quality control, a thorough qualitative and quantitative monitoring of pharmaceutical solid forms is essential to ensure the detection and the quantification of crystalline forms, wither different or with the same chemical composition (polymorphs) at a low detection level. The purpose of this paper was to review and highlight the importance of choosing adequate solid-state techniques for detection and quantification APIs that present polymorphism - based on limits of detection (LOD) and quantification (LOQ), pharmacopeias specifications, international guidelines and studies reported in the literature. To this study, the powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Infrared and Raman spectroscopies and solid-state nuclear magnetic resonance (NMR) were the solid-state techniques analyzed. Additionally, the Argentine, Brazilian, British, European, International, Japanese, Mexican and the United States of America pharmacopeias were reviewed. Based on the analysis performed, the advantages and disadvantages of these techniques, as well as the LOD and LOQ values of APIs were reported. In comparison to these solid-state techniques, reference material used for identification analyses should be previously identified with the corresponding polymorph. Without this previous procedure, the patterns, the spectra, and DSC curves of the reference material can only be used to confirm the mixture of solid forms, not being able to specify which polymorphs are contained in the sample. A major advantage of PXRD is the use of the calculated diffraction patterns obtained from the Crystallographic Information Frameworks (CIFs) files which could be used as a reference pattern without any other information, assistance technique, or physical standards. Regarding the quantification aspect, different pharmacopeias suggest various methods such as the PXRD combining with Rietveld method, which can be used to obtain lower LOD values for minority phases in the mixture of different substances without the need for a calibration curve. Raman spectroscopy can detect polymorphs in small particles and solid-state NMR spectroscopy is a powerful technique for quantification not only crystalline but also crystalline-amorphous mixtures. Finally, this review intends to be a useful tool to control, with efficiency and accuracy, the polymorphism of APIs in pharmaceutical compounds., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: To understand the anomalous behavior of Saquinavir Mesylate (SQVM) in sodium decyl sulfate (SDS) medium during a dissolution test through a crystallographic analysis of the crystal obtained. As a result, it will be possible to elucidate its crystal structure and carry out a complete solid-state characterization of the API., Methods: The solid form obtained was characterized by a structural analysis through X-ray single crystal and powder diffraction. The crystallographic structures of the new salt and the SQVM were compared. In addition, a complete solid-state characterization of SQVM raw material was carried out by techniques such as diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), Raman spectroscopy, scanning electron microscopy and a dissolution method., Results: A new salt consisting of SQVM and SDS was crystallized and its crystal structure was elucidated and reported herein for the first time. The anionic part of SDS interacts with the cationic segment of SQVM to obtain a new salt designated as SQV-DS, which precipitates. The main difference between the two structures occurs in the c-axis expansion, which increases from 15.966 (5) to 21.1924 (14), respectively., Conclusions: Some of the strategies to enhance the dissolution rate of poorly aqueous soluble APIs include the use of surfactants such as SDS in the dissolution medium, as well as in the formulated products. However, there have been constant reports of a dissolution rate slowdown by some surfactants. The interaction mechanisms between the APIs and the dissolution medium containing surfactants need to be carefully investigated in current pharmaceutical formulations. Graphical Abstract., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Irbesartan (IBS) is a tetrazole derivative and antihypertensive drug that has two interconvertible structures, 1H- and 2H-tautomers. The difference between them lies in the protonation of the tetrazole ring. In the solid-state, both tautomers can be isolated as crystal forms A (1H-tautomer) and B (2H-tautomer). Studies have reported that IBS is a polymorphic system and its forms A and B are related monotropically. These reports indicate form B as the most stable and less soluble form. Therefore, the goal of this contribution is to demonstrate through a complete solid-state characterization, thermodynamic study and dissolution properties that the IBS forms are desmotropes that are not related monotropically. However, the intention is also to call attention to the importance of conducting strict chemical and in solid-state quality controls on the IBS raw materials. Hence, powder X-ray diffraction (PXRD) and Raman spectroscopy (RS) at ambient and non-ambient conditions, differential scanning calorimetry (DSC), hot stage microscopy (HSM), Fourier transform infrared (FT-IR) and scanning electron microscopy (SEM) techniques were applied. Furthermore, intrinsic dissolution rate (IDR) and structural stability studies at 98% relative humidity (RH), 25 °C and 40 °C were conducted as well. The results show that in fact, form A is approximately four-fold more soluble than form B. In addition, both IBS forms are stable at ambient conditions. Nevertheless, structural and/or chemical instability was observed in form B at 40 °C and 98% RH. IBS has been confirmed as a desmotropic system rather than a polymorphic one. Consequently, forms A and B are not related monotropically., (© 2019 Xi'an Jiaotong University. Production and hosting by Elsevier B.V.)

Lovastatin (LOV) is a drug used to treat hypercholesterolemia. Recent studies have identified its antioxidant effects and potential use in the treatment of some types of cancer. However, the low bioavailability related to its poor water solubility limits its use in solid oral dosage forms. Therefore, to improve the solubility of LOV three eutectic systems of LOV with the carboxylic acids benzoic (BEN), salicylic (SAL) and cinnamic (CIN) were obtained. Both binary phase and Tammann diagrams were constructed using differential scanning calorimetry (DSC) data of mixtures prepared from 0.1 to 1.0 molar ratios. Binary mixtures and eutectics were prepared by liquid-assisted grinding. The eutectics were further characterized by DSC and powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The LOV-BEN, LOV-SAL and LOV-CIN system formed a eutectic at an LOV mole fraction of 0.19, 0.60 and 0.14, respectively. The systems exhibited improvements in LOV solubility, becoming more soluble by five-fold in the LOV-SAL system and approximately four-fold in the other two systems. Considering that the solubility enhancements and the carboxylic acids used are generally recognized as safe by the U.S. Food and Drug Administration (FDA), the LOV eutectic systems are promising materials to be used in a solubility enhancement strategy for pharmaceutical product formulation.

The experimental conditions necessary for stabilising irbesartan (IBS) tautomers in solution and selectively obtaining the desmotropic crystal forms are presented herein. 1H and 2H tautomers were stabilized in specific solution conditions and the 2H-tetrazole⋯imidazole interaction was confirmed by solution-state NMR. The results showed that highly polar and polarisable solvents (higher values of the electrostatic factor (EF)) lead to the crystallisation of IBS form B. Furthermore, the variations of pH in methanol, in turn, determined the crystallisation of desmotropes A and/or B., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Olanzapine (OLZ), a drug for the treatment of schizophrenia, presents in more than 60 crystal forms. Polymorphs I, II and III were reported, however, the preparation conditions for pure II and III have not been reported. Polymorph IV was reported but this form is actually polymorph II described at different temperature. The diversity of solid forms of OLZ, the change in the nomenclature found in the literature and the presence of polymorphic mixture in samples, increase the difficulty for a correct solid state characterization. Therefore, the goal was the polymorphic identification of three OLZ raw materials, highlighting the limitation of conventional techniques (typically used in analytical control) and the necessity to use a combination of advanced ones to solve this challenge. The samples were studied by conventional techniques such as powder X-ray diffraction, thermoanalytical techniques, infrared spectroscopy. In apart from that, synchrotron powder X-ray diffraction (SPXRD) and solid state nuclear magnetic resonance (ss-NMR) were used. All samples were in accordance with the pharmacopoeia criteria. However, the conventional techniques were not specific for the complete polymorphic identification. Therefore, a combination of advanced techniques (SPXRD and ss-NMR) was necessary to identify the mixture of polymorphs (I, II and III) in all samples., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Clay minerals are layered materials with a number of peculiar properties, which find many relevant applications in various industries. Since they are easily found everywhere, they are particularly attractive due to their economic viability. In the cosmetic industry, clay minerals are often used as excipients to stabilize emulsions or suspensions and to modify the rheological behavior of these systems. They also play an important role as adsorbents or absorbents, not only in cosmetics but also in other industries, such as pharmaceuticals. This reviewer believes that since this manuscript is presented as covering topical applications that include pharmaceuticals, some types of clay minerals should be considered as a potential material to be used as drug delivery systems. We review several applications of clay minerals to dermocosmetic products, relating them to the underlying properties of these materials and exemplifying with a number of clay minerals available in the market. We also discuss the use of clay minerals in topically-applied products for therapeutic purposes, specially for skin treatment and protection., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Various upgrades have been completed at the XRD1 beamline at the Brazilian synchrotron light source (LNLS). The upgrades are comprehensive, with changes to both hardware and software, now allowing users of the beamline to conduct X-ray powder diffraction experiments with faster data acquisition times and improved quality. The main beamline parameters and the results obtained for different standards are presented, showing the beamline ability of performing high-quality experiments in transmission geometry. XRD1 operates in the 5.5-14 keV range and has a photon flux of 7.8 × 10 9  photons s -1 (with 100 mA) at 12 keV, which is one of the typical working energies. At 8 keV (the other typical working energy) the photon flux at the sample position is 3.4 × 10 10  photons s -1 and the energy resolution ΔE/E = 3 × 10 -4 .

Cocrystals of a weakly basic drug (nevirapine) with acidic coformers are shown to alter the solubility dependence on pH, and to exhibit a pHmax above which a less soluble cocrystal becomes more soluble than the drug. The cocrystal solubility advantage can be dialed up or down by solution pH.

Progesterone is a natural hormone steroid used in humans for several treatments and in livestock for artificial insemination, which exhibits two polymorphic forms at ambient conditions: form 1 and form 2. Form 2 is metastable and more soluble than form 1; however, it is not suitable to use as powder raw material because it transforms into form 1 by the effects of grinding. A polymorphic screening of progesterone based on polymer-induced heteronucleation method was performed as an alternative to prepare the metastable form. Polyvinyl alcohol, hydroxypropyl methylcellulose (HPMC), dextran, gelatin, polyisoprene (PI) and acrylonitrile-butadiene (NBR) copolymer were used. Crystals were prepared from 0.5, 10 and 40 mg/mL solutions in acetone at room temperature by solvent evaporation. The samples were characterized by X-ray powder diffraction, differential scanning calorimetry (DSC), scanning electron microcopy and attenuated total reflectance infrared Fourier transform spectroscopy. Form 1 was nucleated from 40 mg/mL solutions on the six polymers and from 10 mg/mL solutions on PI and NBR. The mixture of form 1 and form 2 was obtained from 10 mg/mL solution on HPMC, dextran and gelatin and from 0.5 mg/mL solution crystallizations. Therefore, the polymeric devices, which crystallized the metastable and more soluble polymorph (2) of progesterone, would be a promissory alternative for the pharmaceutical applications.

Polymorphism and particle size distribution can impact the dissolution behaviour and, as a consequence, bioavailability and bioequivalence of poorly soluble drugs, such as Efavirenz (EFV). Nevertheless, these characteristics do not explain some failures occurring in in vitro assays and in in vivo studies. EFV belongs to Class II and the High Activity Antiretroviral Therapy (HAART) is considered the best choice in the treatment of adults and children. EFV is a drug that needs bioequivalence studies for generic compounds. In this work, six raw materials were analyzed and two of them were utilized with human volunteers (in vivo assays or bioequivalence). All the routine pharmaceutical controls of raw materials were approved; however, the reasons for the failure of the bioequivalence assay could not be explained with current knowledge. The aim of this work was to study microstructure, a solid-state property of current interest in the pharmaceutical area, in order to find an explanation for the dissolution and bioequivalence behaviour. The microstructure of EFV raw materials was studied by Whole Powder Pattern Modelling (WPPM) of X-ray powder diffraction data. Results for different EFV batches showed the biorelevance of the crystalline domain size, and a clear correlation with in vitro (dissolution tests) and in vivo assays (bioequivalence)., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Progesterone is a natural steroid hormone and a poor soluble drug which presents two polymorphs (forms 1 and 2). Different methods to obtain form 2 were tested and a complete solid-state characterization of both polymorphs (forms 1 and 2) was conducted. X-ray powder diffraction, hot stage microscopy, Fourier transform infrared, dispersive Raman, (13)C solid-state nuclear magnetic resonance spectroscopy, thermal analysis, scanning electron microscopy techniques and intrinsic dissolution rates (IDR) were applied to investigate physical-chemical and dissolution properties of these two polymorphs. Form 2 was obtained from diluted solutions and from melting after cooling at room temperature. Form 1 was obtained from concentrated solutions and, a mixture of both polymorphs was crystallized from intermediate solutions. The crystal habit was not a distinctive characteristic of each polymorph. The effect of mechanical stress was evaluated in the metastable polymorph (form 2). We observed that grinding form 2 produced seeds of form 1 that induced the transformation of form 2 into form 1 at high temperature. The polymorphic quantification from XRD patterns of ground samples were carried out by the Rietveld method. After grinding and at room temperature conditions (∼25 °C), it was observed the transformation of 17% of form 2 into form 1 in 10 days.

Venlafaxine hydrochloride (VEN) is an antidepressant drug widely used for the treatment of depression. The purpose of this study was to carry out the preparation and solid state characterization of the pure polymorphs (Forms 1 and 2) and the polymorphic identification and quantification of four commercially-available VEN raw materials. These two polymorphic forms were obtained from different crystallization methods and characterized by X-ray Powder Diffraction (XRPD), Diffuse Reflectance Infrared Fourier Transform (DRIFT), Raman Spectroscopy (RS), liquid and solid state Nuclear Magnetic Resonance (NMR and ssNMR) spectroscopies, Differential Scanning Calorimetry (DSC), and Scanning Electron Microscopy (SEM) techniques. The main differences were observed by DSC and XRPD and the latter was chosen as the standard technique for the identification and quantification studies in combination with the Rietveld method for the commercial raw materials (VEN1-VEN4) acquired from different manufacturers. Additionally Form 1 and Form 2 can be clearly distinguished from their (13)C ssNMR spectra. Through the analysis, it was possible to conclude that VEN1 and VEN2 were composed only of Form 1, while VEN3 and VEN4 were a mixture of Forms 1 and 2. Additionally, the Rietveld refinement was successfully applied to quantify the polymorphic ratio for VEN3 and VEN4., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Solid dispersions of saquinavir mesylate containing either Gelucire® 44/14 or poly(ethylene glycol) (PEG) 4000, or mixtures of each carrier with Tween 80 or polyvinyl pyrrolidone (PVP) K30 were prepared in order to enhance the drug dissolution rate. These systems were prepared by the melting method and characterized by X-ray powder diffraction, microscopical techniques, and Raman spectroscopy aiming to establish a relationship between physicochemical and dissolution properties under different cooling conditions. Modifications in degree of crystalline order/disorder over time were observed in preparations with both carriers. Overall, formulations cooled and stored at -20 °C showed less variation in dissolution rates than those at 25 °C. Although Tween 80 has enhanced the known self-emulsifying properties of Gelucire® 44/14, its combination with PEG 4000 displayed miscibility problems. The addition of PVP K30 was not the most effective approach in enhancing the dissolution in early steps; however, the drug dissolution was stable after 7 days of storage at 25 °C. The combination of PEG 4000 and PVP K30 maintained the dissolution properties for 60 and 90 days at 25 °C/95% relative humidity and 40 °C/75% (f₂ values >50), respectively.

In this article, morphology of progesterone polymorphs prepared by polymer-induced heteronucleation (PIHn) technique was studied. Hydroxypropyl methylcellulose(HPMC), such as dextran T-500 and gelatin G-9382, polyisoprene (PI), and acrylonitrile/butadiene copolymer (NBR) were used as substrates. The crystallizations were performed by solvent evaporation at room temperature from 0.5, 10, and 40 mg/ml solutions in chloroform and acetone. Progesterone polymorphs were identified by X-ray diffraction. Differential scanning calorimetry and total attenuated reflectance infrared spectroscopy were used as complementary techniques in the identification. Depending on the polymeric matrix and the concentration used, form 1, form 2, or mixture of both polymorphs were obtained. Scanning electron microscopy pictures evidenced difference in morphology and in homogeneity of the two progesterone polymorphs. These polymorphs prepared by PIHn, did not present a distinctive morphology that allows identifying polymorph by its crystal habit. Hence, polymeric matrix induced the crystallization, affecting polymorphism and morphology., (© Wiley Periodicals, Inc.)

Deflazacort (DFZ), a derivate of prednisolone, is a poorly soluble drug which has been proposed to have major advantages over other corticosteroids. Poorly soluble drugs present limited bioavailability due to their low solubility and dissolution rate and several strategies have been developed in order to find ways to improve them. In general, pharmaceutical laboratories use a micronized process to reduce the particle size in order to increase the dissolution of the drugs. However, this process causes changes such as polymorphic transitions, particle agglomeration and a reduction in fluidity and wettability. These solid-state properties affect the dissolution behavior and stability performance of drugs. Crystallization techniques are widely used in the pharmaceutical industry and antisolvent crystallization has been used to obtain ultrafine particles. In this study, DFZ was investigated in terms of its antisolvent crystallization in different solvents and under various preparation conditions (methanol/water ratio, stirring and evaporation rate, etc.), in order to compare the physicochemical properties between crystallized samples and raw materials available on the Brazilian market with and without micronization. Crystalline structure, morphology, and particle size, and their correlation with the Intrinsic Dissolution Rate (IDR) and dissolution profile as relevant biopharmaceutical properties were studied. Crystallization conditions were achieved which provided crystalline samples of hollow-shaped crystals with internal channels, which increased the dissolution rate of DFZ. The antisolvent crystallization process allowed the formation of hollow crystals, which demonstrated a better dissolution profile than the raw material (crystalline and micronized), making this a promising technique as a crystallization strategy for improving the dissolution and thus the bioavailability of poorly soluble drugs., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Terbinafine hydrochloride (TH), a poorly water soluble antifungal agent, was characterized by solid state techniques including differential scanning calorimetry, thermogravimetry, X-ray powder diffraction, optical and electron microscopies, Fourier transform infrared, Raman and solid-state nuclear magnetic resonance spectroscopies and intrinsic dissolution rate (IDR). A colorless single crystal of TH was grown from an ethanol:water solution and its crystalline structure was determined through X-ray single crystal diffraction. Also, a new crystal habit of TH was obtained through the slow solvent evaporation technique revealing a needle-like shape. A comparison between the IDR results for the TH raw material and TH needle-like crystal revealed lower values for the new crystal habit, which can be attributed to the preferential orientation of the crystals in the compressed disks., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The present study reports the solid-state properties of Fluvastatin sodium salt crystallized from different solvents for comparison with crystalline forms of the commercially available raw material and United States Pharmacopeia (USP) reference standard. Fluvastatin (FLV) samples were characterized by several techniques; such as X-ray powder diffractometry, differential scanning calorimetry, thermogravimetry, liquid and solid-state nuclear magnetic resonance spectroscopy, diffuse reflectance infrared Fourier transform spectroscopy, and scanning electron microscopy. In addition, intrinsic dissolution rate (IDR) of samples was performed in order to study the influence of crystalline form and other factors on rate and extent of dissolution. Three different forms were found. The commercial raw material and Fluvastatin-Acetonitrile (ACN) were identified as "form I" hydrate, the USP reference standard as "form II" hydrate and an ethanol solvate which presented a mixture of phases. Form I, with water content of 4%, was identified as monohydrate.

Due to the physical-chemical and therapeutic impacts of polymorphism, its monitoring in raw materials is necessary. The purpose of this study was to develop and validate a quantitative method to determine the polymorphic content of nimodipine (NMP) raw materials based on differential scanning calorimetry (DSC). The polymorphs required for the development of the method were characterized through DSC, X-ray powder diffraction (XRPD) and Raman spectroscopy and their polymorphic identity was confirmed. The developed method was found to be linear, robust, precise, accurate and specific. Three different samples obtained from distinct suppliers (NMP 1, NMP 2 and NMP 3) were firstly characterized through XRPD and DSC as polymorphic mixtures. The determination of their polymorphic identity revealed that all samples presented the Modification I (Mod I) or metastable form in greatest proportion. Since the commercial polymorph is Mod I, the polymorphic characteristic of the samples analyzed needs to be investigated. Thus, the proposed method provides a useful tool for the monitoring of the polymorphic content of NMP raw materials., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Pharmaceuticals can exist in many solid forms, which can have different physical and chemical properties. These solid forms include polymorphs, solvates, amorphous, and hydrates. Particularly, hydration process can be quite common since pharmaceutical solids can be in contact with water during manufacturing process and can also be exposed to water during storage. In the present work, it is proved that NQR technique is capable of detecting different hydrated forms not only in the pure raw material but also in the final product (tablets), being in this way a useful technique for quality control. This technique was also used to study the dehydration process from pentahydrate to trihydrate.

A new polymorphic form of ciprofloxacin saccharinate (CIP-SAC II) is presented, and compared with CIP-SAC I, a different polymorph which we had previously reported. The characterization techniques used were single crystal and powder X-ray diffraction, differential scanning calorimetry, thermogravimetry analysis and infrared and (13)C solid-state nuclear magnetic resonance spectroscopy. The results obtained from these techniques are consistent. Differential scanning calorimetry and thermogravimetric analysis showed that the reaction between the precursors is completed and the crystalline forms of both salts obtained (I and II) are highly pure. Infrared spectroscopy gave clear evidence of a salt formation. Solid-state nuclear magnetic resonance spectroscopy would indicate some degree of qualitative similarity in the intermolecular interaction scheme in both polymorphs, while thermal analysis data might indicate a difference in quantitative terms. A thorough single crystal structure determination of the new form CIP-SAC II allowed disclosing the most important inter- and intramolecular interactions., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

Latex, a polyisoprene (PI) hydrophobic elastomer, was evaluated in vitro and in vivo as a matrix for intravaginal steroid hormone delivery. Matrices containing hormone were prepared by swelling latex in chloroform that contained soluble progesterone (P4). In vitro studies demonstrate that P4 release from PI follows a zero order model during at least 100 h and depends on initial load up to 10 mg cm(-2). The release of P4 from a PI matrix was found to be two times faster than from a polydimethylsiloxane (PDMS) matrix. FT-IR and X-ray powder diffraction analysis of P4 polymorphs show that when nucleated in PDMS, the hormone crystallizes only in alpha-form while in latex, crystallizes as a mixture of alpha- and beta-form. In vivo studies show that devices with a PI matrix containing 0.5 g of P4 are effective to reach plasma levels above 1 ng ml(-1) that are needed to synchronize estrous in cattle. Altogether, the results show that PI, a vulcanized polymer with a carbon-carbon backbone, can be used as a new matrix for the intravaginal administration of progesterone with improved release profile than silicone and that the matrix can influence the crystalline state of the hormone.

The present 0.25-hydrated form of rosiglitazone maleate [systematic name: (+/-)-2-({2-[2,4-dioxo-1,3-thiazolidin-5-ylmethyl)phenoxy]ethyl}methylamino)pyridinium maleate 0.25-hydrate], C(18)H(20)N(3)O(3)S(+) x C(4)H(3)O(4)(-) x 0.25 H(2)O, is a racemate with two independent moieties in the unit cell. Although the cation geometry does not differ substantially from that in the previously reported hydrochloride, the packing is quite different, the main feature being the formation of hydrogen-bonded tetramers, linked head-to-tail into weakly interacting chains.

The Title Compound (systematic Name: 11-cyclo-propyl-4-methyl-5,11-dihydro-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one butanol 0.3-solvate), C(15)H(14)N(4)O·0.3C(4)H(9)OH, was crystallized in a new triclinic pseudopolymorphic form, a butanol solvate, and the crystal structure determined at 150 K. The mol-ecular conformation of this new form differs from that reported previously, although the main inter-molecular hydrogen-bond pattern remains the same. N-H⋯O hydrogen bonds [N⋯O = 2.957 (3) Å] form centrosymmetric dimers and the crystal packing of this new pseudopolymorph generates infinite channels along the b axis.

The solid state properties of deflazacort (1-(1beta,16alpha)-21-(acetyloxy)-11-hydroxy-2'-methyl-5'H-pregna-1,4-dieno[17,16-d]oxazole-3,20-dione, 1) were investigated using differential scanning calorimetry (DSC), thermogravimetry (TG), single-crystal X-ray diffraction, solid and liquid nuclear magnetic resonance spectroscopy ((13)C NMR), Fourier transform infrared and Raman spectroscopy (FTIR and FT Raman). From the trends observed in the crystal structure and spectral data some conclusions can be made about hydrogen bonding, molecular conformation and crystal packing. Compound 1 crystallizes in an orthorhombic cell, space group P2(1)2(1)2(1) and the following lattice parameters: a=11.2300(5), b=12.8161(8), c=16.171(1)A, V: 2327.4(2)A(3), D(c): 1.260g/cm(3), R1=0.0479, wR2=0.1012. The crystal structure is stabilized by intra and intermolecular interactions, which provides for a very closely packed form. The NMR data indicated that 1 shows a similar conformation in solid and liquid state; while, thermal data revealed that 1 follows a monophasic pattern with a DSC melting peak at 258.4 degrees C (DeltaH 99.7Jg(-1), n=3), indicating that 1 is thermally stable as solid; but, as liquid is unstable to undergo a thermal decomposition reaction. The reactivity of 1 toward light and moisture was examined via DSC and TLC. The data indicated that 1 do not interact with water to give hydrated forms or decomposition products; however, light degrades 1.

Solid-state physical characterization of a pharmaceutical substance is necessary for successful development and approval of the final product. Different physical analytical techniques are available to do so: X-ray diffraction (XRD), IR, Raman, DSC, TG and NMR. Moreover, all of them detect the presence of excipients perturbing the analysis of the pure substance in low doses. In order to study polymorphism and pseudo polymorphism of drug, this paper introduces possible applications of pure nuclear quadrupole resonance, as a non-destructive technique in qualitative and quantitative approaches. Chlorpropamide and diclofenac sodium were used as examples. Unlike the mentioned techniques, the nuclear quadrupole resonance (NQR) signal of pharmaceutical compounds is not perturbed by the presence of solid excipient or other substances unless they possess resonance frequencies in the same frequency range of the compound studied.