Interconvertible Hydrochlorothiazide–Caffeine Multicomponent Pharmaceutical Materials: A Solvent Issue

The design of new multicomponent pharmaceutical materials that involve different active pharmaceutical ingredients (APIs), e.g., drug-drug cocrystals, is a novel and interesting approach to address new therapeutic challenges. In this work, the hydrochlorothiazide-caffeine (HCT–CAF) codrug and its methanol solvate have been synthesized by mechanochemical methods and thoroughly characterized in the solid state by powder and single crystal X-ray diffraction, respectively, as well as differential scanning calorimetry, thermogravimetric analyses and infrared spectroscopy. In addition, solubility and stability studies have also been performed looking for improved physicochemical properties of the codrug. Interestingly, the two reported structures show great similarity, which allows conversion between them. The desolvated HCT–CAF cocrystal shows great stability at 24 h and an enhancement of solubility with respect to the reference HCT API. Furthermore, the contribution of intermolecular forces on the improved physicochemical properties was evaluated by computational methods showing strong and diverse H-bond and π–π stacking interactions.

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Assay and physicochemical characterization of the antiparasitic albendazole

Brazilian Journal of Pharmaceutical Sciences ◽

10.1590/s1984-82502012000200012 ◽

2012 ◽

Vol 48 (2) ◽

pp. 281-290 ◽

Cited By ~ 9

Author(s):

Noely Camila Tavares Cavalcanti ◽

Giovana Damasceno Sousa ◽

Maria Alice Maciel Tabosa ◽

José Lamartine Soares Sobrinho ◽

Leila Bastos Leal ◽

...

Keyword(s):

Physicochemical Characterization ◽

Analytical Techniques ◽

Assay Method ◽

Active Pharmaceutical Ingredients ◽

X Ray Diffraction ◽

Melting Points ◽

X Ray ◽

Pharmaceutical Ingredients ◽

Complementary Techniques

The aim of this study was to characterize three batches of albendazole by pharmacopeial and complementary analytical techniques in order to establish more detailed specifications for the development of pharmaceutical forms. The ABZ01, ABZ02, and ABZ03 batches had melting points of 208 ºC, 208 ºC, and 209 ºC, respectively. X-ray diffraction revealed that all three batches showed crystalline behavior and the absence of polymorphism. Scanning electron microscopy showed that all the samples were crystals of different sizes with a strong tendency to aggregate. The samples were insoluble in water (5.07, 4.27, and 4.52 mg mL-1, respectively) and very slightly soluble in 0.1 M HCl (55.10, 56.90, and 61.70 mg mL-1, respectively) and additionally showed purities within the range specified by the Brazilian Pharmacopoeia 5th edition (F. Bras. V; 98% to 102%). The pharmacopeial assay method was not reproducible and some changes were necessary. The method was validated and showed to be selective, specific, linear, robust, precise, and accurate. From this characterization, we concluded that pharmacopeial techniques alone are not able to detect subtle differences in active pharmaceutical ingredients; therefore, the use of other complementary techniques is required to ensure strict quality control in the pharmaceutical industry.

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Evaluation of Thermal-Induced Polymorphic Transformation on Desloratadine and Desloratadine-Benzoic Acid Salt

Pharmaceutical Sciences ◽

10.34172/ps.2020.59 ◽

2020 ◽

Vol 26 (4) ◽

pp. 399-405

Author(s):

Ahmad Ainurofiq ◽

Rachmat Mauludin ◽

Diky Mudhakir ◽

Sundani Nurono Soewandhi

Keyword(s):

Melting Point ◽

Benzoic Acid ◽

Polymorphic Transformation ◽

Heating Process ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

X Ray ◽

Pharmaceutical Ingredients ◽

Physicochemical Changes ◽

Transformation Methods

Background: Active pharmaceutical ingredients face a challenge in manufacturing due to adverse physicomechanical properties. Desloratadine (DES) form I exhibits poor mechanical behavior through the formation of capping during the tableting process. Salt formation from DES and benzoic acid (BA) has been observed to resolve poor mechanical properties. However, the ability to withstand heat from the manufacturing process should be implemented in DES and DES-BA salt. The aim of this study was to determine the differences between thermal treatment results on DES and DES-BA salt and whether it causes them to undergo polymorphic transformation. Methods: Salt was crystallized between DES and BA using the solvent evaporation method. DES and DES-BA salt were heated at 110°C, 159°C (melting point of DES), 181°C (melting point of DES-BA), and 190°C. Following this, characterization was performed using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and solubility testing. Results: Polymorphic transformation caused by heat occurred in DES, but not in DES-BA salt. The transformation of DES was induced by the effect of heating, which changed polymorph I to a mixture of polymorph I and III at 110°C, to polymorph II at 159°C, and to a mixture of polymorph I, II, and III at 190°C. Under 190oC, DES-BA is still stable and did not undergo a polymorphic transformation. However, at 190oC, decomposition started to occur, which implied decreased solubility, which did not occur in DES. Conclusion: The heating process did not cause DES-BA salt to undergo a polymorphic transformation. However, it caused decomposition at 190oC. DES underwent a polymorphic transformation when exposed to the same condition without decomposition. This provided information to always pay attention to temperature during manufacturing processes that include DES or DES-BA salt to avoid physicochemical changes.

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Melting Diagrams of Adefovir Dipivoxil and Dicarboxylic Acids: An Approach to Assess Cocrystal Compositions

Crystals ◽

10.3390/cryst9020070 ◽

2019 ◽

Vol 9 (2) ◽

pp. 70 ◽

Cited By ~ 2

Author(s):

Hyunseon An ◽

Insil Choi ◽

Il Kim

Keyword(s):

Solid State ◽

Adefovir Dipivoxil ◽

Sufficient Conditions ◽

Dicarboxylic Acids ◽

Current Approach ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

X Ray ◽

Pharmaceutical Ingredients ◽

Solution Crystallization

Pharmaceutical cocrystallization is a useful method to regulate the physical properties of active pharmaceutical ingredients (APIs). Since the cocrystals may form in various API/coformer ratios, identification of the cocrystal composition is the critical first step of any further analysis. However, the composition identification is not always unambiguous if cocrystallization is performed in solid state with unsuccessful solution crystallization. Single melting point and some new X-ray diffraction peaks are necessary but not sufficient conditions. In the present study, the use of melting diagrams coupled with the X-ray diffraction data was tested to identify cocrystal compositions. Adefovir dipivoxil (AD) was used as a model API, and succinic acid (SUC), suberic acid (SUB), and glutaric acid (GLU) were coformers. Compositions of AD/SUC and AD/SUB had been previously identified as 2:1 and 1:1, but that of AD/GLU was not unambiguously identified because of the difficulty of solution crystallization. Melting diagrams were constructed with differential scanning calorimetry, and their interpretation was assisted by powder X-ray diffraction. The cocrystal formation was exhibited as new compositions with congruent melting in the phase diagrams. This method correctly indicated the previously known cocrystal compositions of AD/SUC and AD/SUB, and it successfully identified the AD/GLU cocrystal composition as 1:1. The current approach is a simple and useful method to assess the cocrystal compositions when the crystallization is only possible in solid state.

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Crystal structures ofN-[(4-phenylthiazol-2-yl)carbamothioyl]benzamide andN-{[4-(4-bromophenyl)thiazol-2-yl]carbamothioyl}benzamide from synchrotron X-ray diffraction

Acta Crystallographica Section E Crystallographic Communications ◽

10.1107/s2056989016013396 ◽

2016 ◽

Vol 72 (9) ◽

pp. 1343-1347 ◽

Cited By ~ 1

Author(s):

Ekaterina S. Gantimurova ◽

Alexander S. Bunev ◽

Kristina Yu. Talina ◽

Gennady I. Ostapenko ◽

Pavel V. Dorovatovskii ◽

...

Keyword(s):

Hydrogen Bonds ◽

Three Dimensional ◽

Dihedral Angles ◽

Active Pharmaceutical Ingredients ◽

X Ray Diffraction ◽

Compound I ◽

X Ray ◽

Pharmaceutical Ingredients ◽

Phenyl Rings ◽

Compound Ii

The title compounds, C17H13N3OS2, (I), and C17H12BrN3OS2, (II), are potential active pharmaceutical ingredients. Compound (I) comprises two almost planar fragments. The first is the central (carbamothioyl)amide (r.m.s. deviation = 0.038 Å), and the second consists of the thiazole and two phenyl rings (r.m.s. deviation = 0.053 Å). The dihedral angle between these planes is 15.17 (5)°. Unlike (I), compound (II) comprises three almost planar fragments. The first is the centralN-(thiazol-2-ylcarbamothioyl)amide (r.m.s. deviation = 0.084 Å), and the two others comprise the bromophenyl and phenyl substituents, respectively. The dihedral angles between the central and two terminal planar fragments are 21.58 (7) and 17.90 (9)°, respectively. Both (I) and (II) feature an intramolecular N—H...O hydrogen bond, which closes anS(6) ring. In the crystal of (I), molecules form hydrogen-bonded layers parallel to (100) mediated by N—H...S and C—H...O hydrogen bonds. In the crystal of (II), molecules form a three-dimensional framework mediated by N—H...Br and C—H...O hydrogen bonds, as well as secondary S...Br [3.3507 (11) Å] and S...S [3.4343 (14) Å] interactions.

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X-ray diffraction characterization of different polymorphyc forms of clopidogrel bisulphate in substance and pharmaceutical dosage form

Journal of Research in Physics ◽

10.2478/jrp-2013-0006 ◽

2013 ◽

Vol 37 (1) ◽

pp. 55-60

Author(s):

Olivera R. Klisurića ◽

Srđan J. Rakića ◽

Miroslav J. Cvetinov ◽

Maja M. Stojanović ◽

Andrea R. Nikolić ◽

...

Keyword(s):

Room Temperature ◽

Active Pharmaceutical Ingredients ◽

Stability Studies ◽

X Ray Diffraction ◽

Melting Points ◽

Pharmaceutical Dosage Form ◽

X Ray ◽

Pharmaceutical Ingredients

Abstract The present study deals with the application of X-ray powder diffraction (XRPD) analysis as a technique for identification of the forms of clopidogrel bisulphate (CLP) present in both the active pharmaceutical ingredients (API) and tablets, specifically addressing the question of whether API converts to another form after 12 months of storage. The investigation of the possibility of phase transitions occurring over a temperature range spanning from room temperature to the melting point, both in tablets and pure CLP, were also performed. Tablet samples were observed for the changes in their structure using polarizing optical microscopy, which was also used to determine the melting points of tablet samples. The results gained during this work confirm that XRPD is applicable for API and tablets testing. This is particularly important if we take into account that the method can be used during stability studies, i.e. in order to test the quality of tablets during the validity period.

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Mixed Oxides as Successful Sorption Materials for Some Active Pharmaceutical Ingredients

Chemical and Biochemical Engineering Quarterly ◽

10.15255/cabeq.2020.1774 ◽

2020 ◽

Vol 34 (1) ◽

pp. 25-33

Author(s):

Eva Vrbková ◽

Eliška Vyskočilová ◽

Aneta Semrádová ◽

Lada Sekerová ◽

L. Červený

Keyword(s):

Ascorbic Acid ◽

Mixed Oxides ◽

The Other ◽

Active Pharmaceutical Ingredients ◽

X Ray Diffraction ◽

Solid Supports ◽

X Ray ◽

Pharmaceutical Ingredients ◽

Sorption Material ◽

Different Types

Mixed oxides based on Mg-Al, Mg-Fe, Zn-Al, and Ni-Mg-Al were prepared, characterized and used as sorption materials for different types of active pharmaceutical ingredients (APIs)– nicotinic acid, salicylic acid, ibuprofen, paracetamol and ascorbic acid. Immobilization of APIs on solid supports was confirmed using X-Ray diffraction and infrared spectroscopy. Overall, the best sorption material for mentioned substances showed to be mixed Mg-Al oxides (>80 % of immobilized substance after 4 h except ascorbic acid). On the other hand, Mg-Fe and Mg-Ni-Al materials did not possess high sorption capacity (max. 59 % after 4 h). From studied substances, the immobilization amount was the lowest in the case of ascorbic acid (max. 44 % immobilized after 4 h), the highest amount was immobilized in the case of salicylic and nicotinic acids (>95 %, 4 h). The discussion regarding the structure of substances and properties of sorption materials is also offered.

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Structural Characterization of Co-Crystals of Chlordiazepoxide with p-Aminobenzoic Acid and Lorazepam with Nicotinamide by DSC, X-ray Diffraction, FTIR and Raman Spectroscopy

Pharmaceutics ◽

10.3390/pharmaceutics12070648 ◽

2020 ◽

Vol 12 (7) ◽

pp. 648

Author(s):

Patrycja Garbacz ◽

Dominik Paukszta ◽

Artur Sikorski ◽

Marek Wesolowski

Keyword(s):

Raman Spectroscopy ◽

Water Solubility ◽

Proton Exchange ◽

Aminobenzoic Acid ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

X Ray ◽

Pharmaceutical Ingredients ◽

Crystallization Procedure ◽

Ftir And Raman Spectroscopy

The low water solubility of benzodiazepines seriously affects their bioavailability and, in consequence, their biological activity. Since co-crystallization has been found to be a promising way to modify undesirable properties in active pharmaceutical ingredients, the objective of this study was to prepare co-crystals of two benzodiazepines, chlordiazepoxide and lorazepam. Using different co-crystallization procedures, slurry evaporation and liquid-assisted grinding, co-crystals of chlordiazepoxide with p-aminobenzoic acid and lorazepam with nicotinamide were prepared for the first time. Confirmation that co-crystals were obtained was achieved through a comparison of the data acquired for both co-crystals using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier-transform infrared (FTIR) and Raman spectroscopy, with comparisons acquired for the physical mixtures of both benzodiazepines and coformers. The compatibility of PXRD patterns of both benzodiazepines co-crystals with those contained in the base Powder Diffraction File (PDF-4+) suggests that new crystal structures were indeed created under the co-crystallization procedure. Single-crystal X-ray diffraction revealed that a chlordiazepoxide co-crystal with p-aminobenzoic acid and a lorazepam co-crystal with nicotinamide crystallized in the monoclinic P21/n and P21/c space group, respectively, with one molecule of benzodiazepine and one of coformer in the asymmetric unit. FTIR and Raman spectroscopy corroborated that benzodiazepine and coformer are linked by a hydrogen bond without proton exchange. Furthermore, a DSC study revealed that single endothermic DSC peaks assigned to the melting of co-crystals differ slightly depending on the co-crystallization procedures and solvent used, as well as differing from those of starting components.

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Pharmaceutical Hydrates Analysis—Overview of Methods and Recent Advances

Pharmaceutics ◽

10.3390/pharmaceutics12100959 ◽

2020 ◽

Vol 12 (10) ◽

pp. 959

Author(s):

Ewa Jurczak ◽

Anna Helena Mazurek ◽

Łukasz Szeleszczuk ◽

Dariusz Maciej Pisklak ◽

Monika Zielińska-Pisklak

Keyword(s):

Resonance Spectroscopy ◽

X Ray Diffraction ◽

Hydration Kinetics ◽

Scanning Calorimetry ◽

X Ray ◽

Degree Of Hydration ◽

Pharmaceutical Ingredients ◽

Fourier Transformed Infrared Spectroscopy ◽

Ft Ir ◽

Analytical Approaches

This review discusses a set of instrumental and computational methods that are used to characterize hydrated forms of APIs (active pharmaceutical ingredients). The focus has been put on highlighting advantages as well as on presenting some limitations of the selected analytical approaches. This has been performed in order to facilitate the choice of an appropriate method depending on the type of the structural feature that is to be analyzed, that is, degree of hydration, crystal structure and dynamics, and (de)hydration kinetics. The presented techniques include X-ray diffraction (single crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD)), spectroscopic (solid state nuclear magnetic resonance spectroscopy (ssNMR), Fourier-transformed infrared spectroscopy (FT-IR), Raman spectroscopy), thermal (differential scanning calorimetry (DSC), thermogravimetric analysis (TGA)), gravimetric (dynamic vapour sorption (DVS)), and computational (molecular mechanics (MM), Quantum Mechanics (QM), molecular dynamics (MD)) methods. Further, the successful applications of the presented methods in the studies of hydrated APIs as well as studies on the excipients’ influence on these processes have been described in many examples.

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Studies on the Preparation, Characterization and Solubility of -Cyclodextrin-Roxythromycin Inclusion Complexes

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2009.2.2.5 ◽

2009 ◽

Vol 2 (2) ◽

pp. 523-530

Author(s):

D. Nagasamy Venkatesh ◽

S. Karthick ◽

M. Umesh ◽

G. Vivek ◽

R.M. Valliappan ◽

...

Keyword(s):

Dissolution Rate ◽

Inclusion Complexes ◽

Phase Solubility ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

X Ray ◽

Ir Studies ◽

Poorly Soluble ◽

Poorly Soluble Drug

Roxythromycin/ β-cyclodextrin (Roxy/ β-CD) dispersions were prepared with a view to study the influence of β-CD on the solubility and dissolution rate of this poorly soluble drug. Phase-solubility profile indicated that the solubility of roxythromycin was significantly increased in the presence of β-cyclodextrin and was classified as AL-type, indicating the 1:1 stoichiometric inclusion complexes. Physical characterization of the prepared systems was carried out by differential scanning calorimetry (DSC), X-ray diffraction studies (XRD) and IR studies. Solid state characterization of the drug β-CD binary system using XRD, FTIR and DSC revealed distinct loss of drug crystallinity in the formulation, ostensibly accounting for enhancement of dissolution rate.

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