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Journal articles on the topic 'Pharmaceutical salts'

Author: Grafiati
Published: 4 June 2021
Last updated: 6 September 2023

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1

Boguslavskyi, Ye P., H. L. Voskoboynikova, and A. M. Goy. "Analysis of trends in the positioning of pharmaceutical drugs of the SGLT-2 class of gliflozin derivatives at the pharmaceutical market and the application prospects." Social Pharmacy in Health Care 9, no. 1 (May 19, 2023): 72–83. http://dx.doi.org/10.24959/sphhcj.23.282.

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Aim – is to analyze trends in the use and positioning of pharmaceuticals of the class of gliflozin derivatives on the Ukrainian pharmaceutical market. Materials and methods. In the conducted research, the methods of systematic and comparative analysis, generalization, statistical processing and synthesis were used in determining the projected perspectives, tabular and graphic means of presenting the results. To implement the goal and objectives of the research, software and electronic resources of ATX (Anatomical-Therapeutically-Chemical), ATC (Anatomical Therapeutically Chemical Classification System), BSC (Biopharmaceutical Classification System), Vidal, Compendium, and the State Register of Medicinal Products of Ukraine were used. Results of the research. The results of a systematic analysis of application trends and a comparative analysis of marketing research on the positioning of pharmaceuticals of the class of gliflozin derivatives on regulated markets and the Ukrainian pharmaceutical market are presented. A steady trend in the positioning of the number of appointments in the segments of mono and combined drugs and the number of sales on regulated markets was revealed. It is established that as of the end of 2022, the total number of pharmaceuticals from API class SGLT-2 pharmaceutically acceptable of gliflozin derivatives in the form of solid dosage forms, which are positioned on regulated markets and pharmaceutical campaign research on the pharmaceutical development of new dosage forms of mono and combined drugs is 35, the number of registered pharmaceutical drugs in Ukraine is 4 mono and 2 combined drugs. The segment of this group of drugs - mono and combined drugs - has been systematized, according to the ATX classification by active substances - API - pharmaceutically acceptable salts of gliflozin derivatives on regulated markets and on the pharmaceutical market of Ukraine. Conclusions. The analysis of positioning on regulated markets and statistics of R&D research of pharmaceutical companies for the development of new dosage forms of mono and combined drugs provides grounds to generalize and conclude that SGLT-2 inhibitors are the newest and promising class of antidiabetic drugs, which, according to evidence-based medicine, are used in combination with with insulin and other antidiabetic drugs in the treatment of diabetes mellitus (DM) of I and II types, in combined regimens with metformin and DPP-4 inhibitors, as well as in combinations of all three and TZD drugs. SGLT-2 inhibitors are the second largest group of antidiabetic agents by the volume of clinical trials, which is 12%. Recommended for use by FDA regulatory authorities, EMA is an API of the SGLT-2 class of pharmaceutically acceptable derivatives of gliflozin: canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, luseogliflozin, tofogliflozin, sotagliflozin, as well as pharmaceutically acceptable salts; remogliflozin etabonate; sergliflozin etabonate. It has been established that SGLT-2 API drugs of pharmaceutically acceptable derivatives of gliflozin have a constant trend of positioning the number of appointments in the segments of mono and combined drugs and the number of sales on regulated markets, the total amount is 35 in the form of solid dosage forms. Distribution by volume of sales of solid dosage forms of pharmaceutical preparations with API class SGLT-2 of pharmaceutically acceptable of gliflozin derivatives is: tableted monopreparations – 59.2%; combined – 37.2%; mono preparations, hard capsules - 3.6%. The number of registered pharmaceutical drugs in Ukraine is 4 mono and 2 combined drugs, the level of prices from a pharmacoeconomic point of view, according to the results of price comparison of other antihyperglycemic drugs, are not affordable for Ukrainian patients who need systemic use. Therefore, the increase in the range of SGLT-2 class API drugs of pharmaceutically acceptable gliflozin derivatives on the Ukrainian pharmaceutical market and competitive manufacturers will contribute to the availability of use for the treatment of DM in Ukrainian patients. Key words: trends; positioning; application; pharmaceutically acceptable derivatives of gliflozin; drug support; best practice; evidence-based medicine; rational pharmacotherapy.
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2

Jaśkowska, Jolanta, Przemysław Zaręba, Anna Drabczyk, Agnieszka Kozak, Izabela D. Madura, Zbigniew Majka, and Edyta Pindelska. "New Pharmaceutical Salts of Trazodone." Molecules 26, no. 3 (February 2, 2021): 769. http://dx.doi.org/10.3390/molecules26030769.

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New pharmaceutically acceptable salts of trazodone (trazodone hydrogen bromide and trazodone 1-hydroxy-2-naphthonic acid) for the treatment of central nervous system disorders are synthesized and described. Although trazodone salts are poorly crystalline, single-crystal X-ray diffraction data for trazodone 1-hydroxy-2-naphthonic acid were collected and analyzed as well as compared to the previously described crystal structure of commercially available trazodone hydrochloride. The powder samples of all new salts were characterized by Fourier transform infrared spectroscopy, X-ray diffraction and 13C solid-state nuclear magnetic resonance spectroscopy. Spectroscopic studies were supported by gauge including projector augmented wave (GIPAW) calculations of carbon chemical shielding constants. The main goal of our research was to find salts with better physicochemical properties and to make an attempt to associate them with both the anion structure and the most prominent interactions exhibited by the protonated trazodone cation. The dissolution profiles of trazodone from tablets prepared from various salts with lactose monohydrate were investigated. The studies revealed that salts with simple anions show a fast release of the drug while the presence of more complex anion, more strongly interacting with the cation, effects a slow-release profile of the active substance and can be used for the preparation of the tables with a delay or prolonged mode of action.
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3

Cvetkovski, Aleksandar, Valeria Ferretti, and Valerio Bertolasi. "New pharmaceutical salts containing pyridoxine." Acta Crystallographica Section C Structural Chemistry 73, no. 12 (November 8, 2017): 1064–70. http://dx.doi.org/10.1107/s2053229617015765.

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Two mixed crystals were obtained by crystallizing the active pharmaceutical ingredient pyridoxine [systematic name: 4,5-bis(hydroxymethyl)-2-methylpyridin-3-ol, PN] with (E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoic acid (ferulic acid) and 4-hydroxy-3,5-dimethoxybenzoic acid (syringic acid). PN and the coformers crystallize in the form of pharmaceutical salts in a 1:1 stoichiometric ratio, namely 3-hydroxy-4,5-bis(hydroxymethyl)-2-methylpyridin-1-ium (E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoate, C8H12NO3 +·C9H9O5 −, and 3-hydroxy-4,5-bis(hydroxymethyl)-2-methylpyridin-1-ium 4-hydroxy-3,5-dimethoxybenzoate monohydrate, C8H12NO3 +·C10H11O5 −·H2O, the proton exchange between PN and the acidic partner being supported by the differences of the pK a values of the two components and by the C—O bond lengths of the carboxylate groups. Besides complex hydrogen-bonding networks, π–π interactions between aromatic moieties have been found to be important for the packing architecture in both crystals. Hirshfeld surface analysis was used to explore the intermolecular interactions in detail and compare them with the interactions found in similar pyridoxine/carboxylic acid salts.
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4

Bolla, Geetha, and Ashwini Nangia. "Novel pharmaceutical salts of albendazole." CrystEngComm 20, no. 41 (2018): 6394–405. http://dx.doi.org/10.1039/c8ce01311j.

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Novel pharmaceutical salts of albendazole drugs are crystallized with sulfonic acids and carboxylic acids. The disorder of the thiopropyl chain in the parent crystal structure is resolved in the salt crystal structures.
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5

Basavoju, Srinivas, Dan Boström, and Sitaram P. Velaga. "Pharmaceutical Cocrystal and Salts of Norfloxacin." Crystal Growth & Design 6, no. 12 (December 2006): 2699–708. http://dx.doi.org/10.1021/cg060327x.

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6

Pang, Hong, Yu-Bin Sun, Jun-Wen Zhou, Meng-Juan Xie, Hao Lin, Yan Yong, Liang-Zhu Chen, and Bing-Hu Fang. "Pharmaceutical Salts of Enrofloxacin with Organic Acids." Crystals 10, no. 8 (July 27, 2020): 646. http://dx.doi.org/10.3390/cryst10080646.

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Enrofloxacin is a poorly soluble antibacterial drug of the fluoroquinolones class used in veterinary medicine. The main purpose of this work was to investigate the structural and pharmaceutical properties of new enrofloxacin salts. Enrofloxacin anhydrate and its organic salts with tartaric acid, nicotinic acid and suberic acid formed as pure crystalline anhydrous solids. All the crystals were grown from a mixed solution by slow evaporation at room temperature. These products were then characterized by field-emission scanning electron microscopy, powder X-ray diffraction, Fourier transform infrared spectroscopy and differential scanning calorimetry. Further, X-ray single crystal diffraction analysis was used to study the crystal structure. The intermolecular interactions and packing arrangements in the crystal structures were studied, and the solubility of these salts in water was determined using high-performance liquid chromatography. The results show that the new salts of enrofloxacin developed in this study exhibited excellent water solubility.
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7

Khandavilli, U. B. Rao, Leila Keshavarz, Eliška Skořepová, René R. E. Steendam, and Patrick J. Frawley. "Organic Salts of Pharmaceutical Impurity p-Aminophenol." Molecules 25, no. 8 (April 21, 2020): 1910. http://dx.doi.org/10.3390/molecules25081910.

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The presence of impurities can drastically affect the efficacy and safety of pharmaceutical entities. p-Aminophenol (PAP) is one of the main impurities of paracetamol (PA) that can potentially show toxic effects such as maternal toxicity and nephrotoxicity. The removal of PAP from PA is challenging and difficult to achieve through regular crystallization approaches. In this regard, we report four new salts of PAP with salicylic acid (SA), oxalic acid (OX), l-tartaric acid (TA), and (1S)-(+)-10-camphorsulfonic acid (CSA). All the PAP salts were analyzed using single-crystal X-ray diffraction, powder X-ray diffraction, infrared spectroscopy, differential scanning calorimetry, and thermogravimetric analysis. The presence of minute amounts of PAP in paracetamol solids gives a dark color to the product that was difficult to remove through crystallization. In our study, we found that the addition of small quantities of the aforementioned acids helps to remove PAP from PA during the filtration and washings. This shows that salt formation could be used to efficiently remove challenging impurities.
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8

Choudhury, Angshuman Roy, Maheswararao Karanam, Mayank Joshi, Indu Verma, Aakanksha Gulati, Chesta Budhwar, Sushmita Rani, et al. "Pharmaceutical cocrystallization: polymorphs, salts and co-crystals." Acta Crystallographica Section A Foundations and Advances 77, a2 (August 14, 2021): C878. http://dx.doi.org/10.1107/s0108767321088206.

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9

Manin, Alex N., Alexander P. Voronin, Ksenia V. Drozd, Andrei V. Churakov, and German L. Perlovich. "Pharmaceutical salts of emoxypine with dicarboxylic acids." Acta Crystallographica Section C Structural Chemistry 74, no. 7 (June 5, 2018): 797–806. http://dx.doi.org/10.1107/s2053229618007386.

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New salt forms of the antioxidant drug emoxypine (EMX, 2-ethyl-6-methylpyridin-3-ol) with pharmaceutically acceptable maleic (Mlt), malonic (Mln) and adipic (Adp) acids were obtained {emoxypinium maleate, C8H12NO+·C4H3O4 −, [EMX+Mlt], emoxypinium malonate, C8H12NO+·C3H3O4 −, [EMX+Mln], and emoxypinium adipate, C8H12NO+·C6H9O4 −, [EMX+Adp]} and their crystal structures determined. The molecular packing in the three EMX salts was studied by means of solid-state density functional theory (DFT), followed by QTAIMC (quantum theory of atoms in molecules and crystals) analysis. It was found that the major contribution to the packing energy comes from pyridine–carboxylate and hydroxy–carboxylate heterosynthons forming infinite one-dimensional ribbons, with [EMX+Adp] additionally stabilized by hydrogen-bonded C(9) chains of Adp− ions. The melting processes of the [EMX+Mlt] (1:1), [EMX+Mln] (1:1) and [EMX+Adp] (1:1) salts were studied and the fusion enthalpy was found to increase with the increase of the calculated lattice energy. The dissolution process of the EMX salts in buffer (pH 7.4) was also studied. It was found that the formation of binary crystals of EMX with dicarboxylic acids increases the EMX solubility by more than 30 times compared to its pure form.
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10

Allu, Suryanarayana, Geetha Bolla, Srinu Tothadi, and Ashwini K. Nangia. "Novel Pharmaceutical Cocrystals and Salts of Bumetanide." Crystal Growth & Design 20, no. 2 (December 16, 2019): 793–803. http://dx.doi.org/10.1021/acs.cgd.9b01195.

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11

Bucci, R., A. D. Magrì, and A. L. Magrì. "Determination of diclofenac salts in pharmaceutical formulations." Fresenius' Journal of Analytical Chemistry 362, no. 7-8 (December 1, 1998): 577–82. http://dx.doi.org/10.1007/s002160051127.

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12

Surov, Artem O., Alex N. Manin, Alexander P. Voronin, Ksenia V. Drozd, Anna A. Simagina, Andrei V. Churakov, and German L. Perlovich. "Pharmaceutical salts of ciprofloxacin with dicarboxylic acids." European Journal of Pharmaceutical Sciences 77 (September 2015): 112–21. http://dx.doi.org/10.1016/j.ejps.2015.06.004.

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13

Fini, Adamo, Giuseppe Fazio, Francesca Rosetti, M. Angeles Holgado, Ana Iruín, and Josefa Alvarez-Fuentes. "Diclofenac Salts. III. Alkaline and Earth Alkaline Salts." Journal of Pharmaceutical Sciences 94, no. 11 (November 2005): 2416–31. http://dx.doi.org/10.1002/jps.20436.

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14

Fini, Adamo, Cristina Cavallari, Glenda Bassini, Francesca Ospitali, and Rita Morigi. "Diclofenac Salts, Part 7: Are the Pharmaceutical Salts with Aliphatic Amines Stable?" Journal of Pharmaceutical Sciences 101, no. 9 (September 2012): 3157–68. http://dx.doi.org/10.1002/jps.23052.

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15

Babor, Martin, Philipp P. Nievergelt, Jan Čejka, Vít Zvoníček, and Bernhard Spingler. "Microbatch under-oil salt screening of organic cations: single-crystal growth of active pharmaceutical ingredients." IUCrJ 6, no. 1 (January 1, 2019): 145–51. http://dx.doi.org/10.1107/s2052252518017876.

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Multicomponent solid forms of active pharmaceutical ingredients represent a modern method of tuning their physicochemical properties. Typically, salts are the most commonly used multicomponent solid form in the pharmaceutical industry. More than 38% are formulated as organic cations. Salt screening is an essential but demanding step when identifying the most appropriate formulation. The microbatch under-oil crystallization technique of proteins has been combined with the previously developed high-throughput vapour-diffusion screening for use as a novel method of primary salt screening of organic cations. The procedure allows the set up of about 100 crystallization experiments per 30 min. This requires between 17 and 564 mg of screened cationic active pharmaceutical ingredients, which were of moderate to very high water solublity. Five distinct organic salts, three of them diverse active pharmaceutical compounds or the other enantiomer thereof, in the form of chloride salts were tested. The screening was extremely successful; at least two new single-crystal structures could be obtained for each particular compound and many more salts as single crystals were formed compared with our previous vapour-diffusion method.
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16

Bharate, Sonali S. "Carboxylic Acid Counterions in FDA-Approved Pharmaceutical Salts." Pharmaceutical Research 38, no. 8 (July 23, 2021): 1307–26. http://dx.doi.org/10.1007/s11095-021-03080-2.

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17

Mishnev, A., I. Kalvins, L. Aleksejeva, and A. Lebedev. "Structure of mildronate, its pharmaceutical salts and cocrystals." Acta Crystallographica Section A Foundations of Crystallography 67, a1 (August 22, 2011): C567. http://dx.doi.org/10.1107/s0108767311085655.

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18

Hiendrawan, Stevanus, Edward Widjojokusumo, Bambang Veriansyah, and Raymond R. Tjandrawinata. "Pharmaceutical Salts of Carvedilol: Polymorphism and Physicochemical Properties." AAPS PharmSciTech 18, no. 4 (September 6, 2016): 1417–25. http://dx.doi.org/10.1208/s12249-016-0616-x.

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19

Pindelska, Edyta, Agnieszka Sokal, and Waclaw Kolodziejski. "Pharmaceutical cocrystals, salts and polymorphs: Advanced characterization techniques." Advanced Drug Delivery Reviews 117 (August 2017): 111–46. http://dx.doi.org/10.1016/j.addr.2017.09.014.

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20

Omer, M. E., A. M. Qandil, A. S. Ali, and H. J. Habib. "Preparation and solubility profile study of sodium and potassium salts of mefenamic acid: the effect of pH and polarity." Digest Journal of Nanomaterials and Biostructures 16, no. 2 (2021): 443–54. http://dx.doi.org/10.15251/djnb.2021.162.443.

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Enhancing the solubility of active pharmaceutical ingredients became a fundamental concept in the manufacturing of different pharmaceutical dosage forms. This research aims to enhance the solubility of mefenamic acid by salt formation method and study the effect of polarity, pH, and temperature on the solubility of mefenamic acid and its salts. Two deferent salts of mefenamic acid (sodium and potassium salts) were prepared. Using the asymmetric factorial as an experimental design, the solubility of mefenamic acid (MA), sodium mefenamate (Na-MA), and potassium mefenamate (K-MA) were studied in different solvents, pH, and temperatures. It has been found that potassium mefenamate has the highest solubility among other derivatives in different media. Also, the mefenamic acid and its salts have a higher solubility in the polar aprotic solvent and the higher pH aqueous media.
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21

Yao, Xin, Amy Lan Neusaenger, and Lian Yu. "Amorphous Drug-Polymer Salts." Pharmaceutics 13, no. 8 (August 17, 2021): 1271. http://dx.doi.org/10.3390/pharmaceutics13081271.

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Amorphous formulations provide a general approach to improving the solubility and bioavailability of drugs. Amorphous medicines for global health should resist crystallization under the stressful tropical conditions (high temperature and humidity) and often require high drug loading. We discuss the recent progress in employing drug–polymer salts to meet these goals. Through local salt formation, an ultra-thin polyelectrolyte coating can form on the surface of amorphous drugs, immobilizing interfacial molecules and inhibiting fast crystal growth at the surface. The coated particles show improved wetting and dissolution. By forming an amorphous drug–polymer salt throughout the bulk, stability can be vastly enhanced against crystallization under tropical conditions without sacrificing the dissolution rate. Examples of these approaches are given, along with suggestions for future work.
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22

Seaton, Colin C., Rayan R. Thomas, Eman A. A. Essifaow, Elisa Nauha, Tasnim Munshi, and Ian J. Scowen. "Structural motifs in salts of sulfathiazole: implications for design of salt forms in pharmaceuticals APIs." CrystEngComm 20, no. 24 (2018): 3428–34. http://dx.doi.org/10.1039/c8ce00606g.

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The creation of salts is a frequently used approach to modify physicochemical properties of active pharmaceutical ingredients. This work prepares a collection of sulfathiazole salts to probe the influence of counterion structure on crystal packing.
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23

Deng, Yuehua, Shiyuan Liu, Yanbin Jiang, Inês C. B. Martins, and Thomas Rades. "Recent Advances in Co-Former Screening and Formation Prediction of Multicomponent Solid Forms of Low Molecular Weight Drugs." Pharmaceutics 15, no. 9 (August 22, 2023): 2174. http://dx.doi.org/10.3390/pharmaceutics15092174.

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Multicomponent solid forms of low molecular weight drugs, such as co-crystals, salts, and co-amorphous systems, are a result of the combination of an active pharmaceutical ingredient (API) with a pharmaceutically acceptable co-former. These solid forms can enhance the physicochemical and pharmacokinetic properties of APIs, making them increasingly interesting and important in recent decades. Nevertheless, predicting the formation of API multicomponent solid forms in the early stages of formulation development can be challenging, as it often requires significant time and resources. To address this, empirical and computational methods have been developed to help screen for potential co-formers more efficiently and accurately, thus reducing the number of laboratory experiments needed. This review provides a comprehensive overview of current screening and prediction methods for the formation of API multicomponent solid forms, covering both crystalline states (co-crystals and salts) and amorphous forms (co-amorphous). Furthermore, it discusses recent advances and emerging trends in prediction methods, with a particular focus on artificial intelligence.
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24

Gupta, Deepak, Deepak Bhatia, Vivek Dave, Vijaykumar Sutariya, and Sheeba Varghese Gupta. "Salts of Therapeutic Agents: Chemical, Physicochemical, and Biological Considerations." Molecules 23, no. 7 (July 14, 2018): 1719. http://dx.doi.org/10.3390/molecules23071719.

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The physicochemical and biological properties of active pharmaceutical ingredients (APIs) are greatly affected by their salt forms. The choice of a particular salt formulation is based on numerous factors such as API chemistry, intended dosage form, pharmacokinetics, and pharmacodynamics. The appropriate salt can improve the overall therapeutic and pharmaceutical effects of an API. However, the incorrect salt form can have the opposite effect, and can be quite detrimental for overall drug development. This review summarizes several criteria for choosing the appropriate salt forms, along with the effects of salt forms on the pharmaceutical properties of APIs. In addition to a comprehensive review of the selection criteria, this review also gives a brief historic perspective of the salt selection processes.
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25

Nie, Haichen, Stephen R. Byrn, and Qi (Tony) Zhou. "Stability of pharmaceutical salts in solid oral dosage forms." Drug Development and Industrial Pharmacy 43, no. 8 (April 18, 2017): 1215–28. http://dx.doi.org/10.1080/03639045.2017.1304960.

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26

Basavoju, Srinivas, Dan Boström, and Sitaram P. Velaga. "Pharmaceutical Salts of Fluoroquinolone Antibacterial Drugs with Acesulfame Sweetener." Molecular Crystals and Liquid Crystals 562, no. 1 (July 30, 2012): 254–64. http://dx.doi.org/10.1080/10426507.2012.669673.

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27

Wood, Peter A., Mark A. Oliveira, Andrina Zink, and Magali B. Hickey. "Isostructurality in pharmaceutical salts: How often and how similar?" CrystEngComm 14, no. 7 (2012): 2413. http://dx.doi.org/10.1039/c2ce06588f.

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28

Schwalbe, Carl, Miren Ramirez, Barbara Conway, and Peter Timmins. "Crystal packing and pharmaceutical properties of salts of diclofenac." Acta Crystallographica Section A Foundations and Advances 73, a1 (May 26, 2017): a134. http://dx.doi.org/10.1107/s0108767317098671.

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29

Fini, A., M. Garuti, G. Fazio, J. Alvarez‐Fuentes, and M. A. Holgado. "Diclofenac salts. I. fractal and thermal analysis of sodium and potassium diclofenac salts." Journal of Pharmaceutical Sciences 90, no. 12 (December 2001): 2049–57. http://dx.doi.org/10.1002/jps.1156.

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30

Reddy, J. Satyanarayana, Saraswatula Viswanadha Ganesh, Ravikumar Nagalapalli, Rambabu Dandela, K. Anand Solomon, K. Anil Kumar, N. Rajesh Goud, and Ashwini Nangia. "Fluoroquinolone salts with carboxylic acids." Journal of Pharmaceutical Sciences 100, no. 8 (August 2011): 3160–76. http://dx.doi.org/10.1002/jps.22537.

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31

Borys, Varynskyi, Kaplaushenko Andriy, and Parchenko Vladymyr. "ELECTROSPRAY IONIZATION MASS SPECTROMETRY FRAGMENTATION PATHWAYS OF SALTS OF SOME 1,2,4-TRIAZOLYLTHIOACETATE ACIDS, THE ACTIVE PHARMACEUTICAL INGREDIENTS." Asian Journal of Pharmaceutical and Clinical Research 11, no. 10 (October 7, 2018): 303. http://dx.doi.org/10.22159/ajpcr.2018.v11i10.16564.

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Objective: The goal of this research was to study fragmentation pathways of series salts of 1,2,4-triazolylthioacetate acids. Methods: The study was done in the Electrospray ionization source with single quadrupole mass spectrometer Agilent 6120 after elution through column Zorbax SB-C18, 30 mm × 4.6 mm, 1.8 μm at Agilent 1260 infinity high-performance liquid chromatography system. The series salts of 1,2,4-triazolylthioacetate acids were studied. These salts are active pharmaceutical ingredients of potential or registered pharmaceutical formulations. Results: The mass spectra of corresponding compounds have analyzed. The fragmentation patterns of these compounds decay have proposed. Conclusions: Studying the fragmentation of the indicated substances can be used for detecting the mentioned substances, as well as for confirming the structure of new compounds with the mass spectrum based on the patterns described above.
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32

Bhalani, Dixit, Bhingaradiya Nutan, Avinash Kumar, and Arvind Singh Chandel. "Bioavailability Enhancement Techniques for Poorly Aqueous Soluble Drugs and Therapeutics." Biomedicines 10, no. 9 (August 23, 2022): 2055. http://dx.doi.org/10.3390/biomedicines10092055.

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The low water solubility of pharmacoactive molecules limits their pharmacological potential, but the solubility parameter cannot compromise, and so different approaches are employed to enhance their bioavailability. Pharmaceutically active molecules with low solubility convey a higher risk of failure for drug innovation and development. Pharmacokinetics, pharmacodynamics, and several other parameters, such as drug distribution, protein binding and absorption, are majorly affected by their solubility. Among all pharmaceutical dosage forms, oral dosage forms cover more than 50%, and the drug molecule should be water-soluble. For good therapeutic activity by the drug molecule on the target site, solubility and bioavailability are crucial factors. The pharmaceutical industry’s screening programs identified that around 40% of new chemical entities (NCEs) face various difficulties at the formulation and development stages. These pharmaceuticals demonstrate less solubility and bioavailability. Enhancement of the bioavailability and solubility of drugs is a significant challenge in the area of pharmaceutical formulations. According to the Classification of Biopharmaceutics, Class II and IV drugs (APIs) exhibit poor solubility, lower bioavailability, and less dissolution. Various technologies are discussed in this article to improve the solubility of poorly water-soluble drugs, for example, the complexation of active molecules, the utilization of emulsion formation, micelles, microemulsions, cosolvents, polymeric micelle preparation, particle size reduction technologies, pharmaceutical salts, prodrugs, the solid-state alternation technique, soft gel technology, drug nanocrystals, solid dispersion methods, crystal engineering techniques and nanomorph technology. This review mainly describes several other advanced methodologies for solubility and bioavailability enhancement, such as crystal engineering, micronization, solid dispersions, nano sizing, the use of cyclodextrins, solid lipid nanoparticles, colloidal drug delivery systems and drug conjugates, referring to a number of appropriate research reports.
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33

Skorepova, Eliska, Michal Husak, Ludek Ridvan, and Jan Cejka. "Salts and Co-Crystals of Agomelatine." Acta Crystallographica Section A Foundations and Advances 70, a1 (August 5, 2014): C1024. http://dx.doi.org/10.1107/s205327331408975x.

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Salts and co-crystal are multicomponent solids but in different ionization states. In salts, there is a proton transfer between the molecular components, making it contain cations and anions. On the other hand, co-crystals are made up from neutral molecules held together by non-bonded interactions. Agomelatine is an active pharmaceutical ingredient (API) used as an antidepressant. Because the search for new solid forms of an API is an important step in a drug development, our aim was to prepare novel co-crystals of agomelatine. Phase analysis was done by powder X-ray diffraction and the structures were solved from single-crystal X-ray diffraction data. Further analyses were done by infrared and Raman spectroscopy and solid state NMR. For agomelatine, several co-crystals have been prepared, namely with citric acid, maleic acid, oxalic acid, 4-hydroxybenzoic acid and isonicotinamide. Agomelatine is an amidic compound and, since amides are considered very neutral, it was quite a surprise, when agomelatine in the combination with benzensulphonic, hydrobromic and hydroiodic acids produced salts. Structural comparison of all the solid phases in the respect of ΔpKA, amidic group bond lengths, conformation and packing of agomelatine and position of the guest molecule in the crystal lattice is also given. For pharmaceuticals, the determination whether the material is a salt or a co-crystal is interesting not only academically, but also from the regulatory point of view. Therefore, our findings may play a crucial role in the future development of the multicomponent solid phases of agomelatine. This work was supported by the Grant Agency of Czech Republic, Grant No. 106/14/03636S and the specific university research, Grant No. A2-FCHT-2014-081.
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Yu, Mingchao, Meidai Liang, Qi An, Wenwen Wang, Baoxi Zhang, Shiying Yang, Jian Zhou, et al. "Versatile Solid Modifications of Multicomponent Pharmaceutical Salts: Novel Metformin–Rhein Salts Based on Advantage Complementary Strategy Design." Pharmaceutics 15, no. 4 (April 9, 2023): 1196. http://dx.doi.org/10.3390/pharmaceutics15041196.

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This study aimed to develop an effective treatment for diabetes and diabetic complications, based on the advantage complementary strategy of drug–drug salt, by designing and synthesizing the multicomponent molecular salts containing metformin (MET) and rhein (RHE). Finally, the salts of MET–RHE (1:1), MET–RHE–H2O (1:1:1), MET–RHE–ethanol–H2O (1:1:1:1), and MET–RHE–acetonitrile (2:2:1) were obtained, indicating the polymorphism of salts formed by MET and RHE. The structures were analyzed by the combination of characterization experiments and theoretical calculation, and the formation mechanism of polymorphism was discussed. The obtained results of in vitro evaluation showed that MET–RHE had a similar hygroscopicity with metformin hydrochloride (MET·HCl), and the solubility of the component of RHE increased by approximately 93 times, which laid a foundation for improving the bioavailability of MET and RHE in vivo. The evaluation of hypoglycemic activity in mice (C57BL/6N) indicated that MET–RHE exhibited better hypoglycemic activity than the parent drugs and the physical mixtures of MET and RHE. The above findings demonstrate that this study achieved the complementary advantages of MET and RHE through the multicomponent pharmaceutical salification technique, and provides new possibilities for the treatment of diabetic complications.
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Hua, Xiu-Ni, Xia Pan, Yang Zhu, Zhuoer Cai, Qi Song, Yaozhenhui Li, Wenbin Feng, Xin Chen, Hui Zhang, and Baiwang Sun. "Novel pharmaceutical salts of cephalexin with organic counterions: structural analysis and properties." RSC Advances 12, no. 54 (2022): 34843–50. http://dx.doi.org/10.1039/d2ra05565a.

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36

Nagata, Mariko, Toshihisa Yotsuyanagi, and Ken Ikeda. "Solubilization of Vitamin K1 by Bile Salts and Phosphatidylcholine-Bile Salts Mixed Micelles." Journal of Pharmacy and Pharmacology 40, no. 2 (February 1988): 85–88. http://dx.doi.org/10.1111/j.2042-7158.1988.tb05186.x.

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37

Guo, Yiwang, and Changquan Calvin Sun. "Pharmaceutical Lauryl Sulfate Salts: Prevalence, Formation Rules, and Formulation Implications." Molecular Pharmaceutics 19, no. 2 (October 21, 2021): 432–39. http://dx.doi.org/10.1021/acs.molpharmaceut.1c00690.

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38

Avdeef, Alex. "Disproportionation of Pharmaceutical Salts: pHmax and Phase-Solubility/pH Variance." Molecular Pharmaceutics 18, no. 7 (June 18, 2021): 2724–43. http://dx.doi.org/10.1021/acs.molpharmaceut.1c00258.

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39

Rocheleau, Marie-Josee. "Analytical Methods for Determination of Counter-ions in Pharmaceutical Salts." Current Pharmaceutical Analysis 4, no. 1 (February 1, 2008): 25–32. http://dx.doi.org/10.2174/157341208783497560.

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40

de Melo, Cristiane C., Paulo de Sousa Carvalho, Luan F. Diniz, Richard F. D'Vries, Alejandro P. Ayala, and Javier Ellena. "Supramolecular synthesis and thermochemical investigations of pharmaceutical inorganic isoniazid salts." CrystEngComm 18, no. 34 (2016): 6378–88. http://dx.doi.org/10.1039/c6ce00969g.

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41

Joshi, Mayank, and Angshuman Roy Choudhury. "Salts of Amoxapine with Improved Solubility for Enhanced Pharmaceutical Applicability." ACS Omega 3, no. 2 (February 27, 2018): 2406–16. http://dx.doi.org/10.1021/acsomega.7b02023.

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42

He, Yan, Chris Ho, Donglai Yang, Jeane Chen, and Edward Orton. "Measurement and Accurate Interpretation of the Solubility of Pharmaceutical Salts." Journal of Pharmaceutical Sciences 106, no. 5 (May 2017): 1190–96. http://dx.doi.org/10.1016/j.xphs.2017.01.023.

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43

Joshi, Mayank, and Angshuman Roy Choudhury. "Salts of amoxapine with improved solubility for enhanced pharmaceutical applicability." Acta Crystallographica Section A Foundations and Advances 73, a2 (December 1, 2017): C208. http://dx.doi.org/10.1107/s2053273317093652.

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44

Fujinuma, Kenta, Yuji Ishii, Yasuo Yashihashi, Estuo Yonemochi, Kiyohiko Sugano, and Katsuhide Tarada. "Triboelectrification of active pharmaceutical ingredients: week acids and their salts." International Journal of Pharmaceutics 493, no. 1-2 (September 2015): 434–38. http://dx.doi.org/10.1016/j.ijpharm.2015.08.008.

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45

Nunes, Paulo, Pedro Henrique de Oliveira Santiago, Cecilia Carolina Pinheiro da Silva, and Javier Ellena. "Drug Repurposing of the Antiviral Drug Acyclovir: New Pharmaceutical Salts." Crystals 13, no. 5 (May 8, 2023): 782. http://dx.doi.org/10.3390/cryst13050782.

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Drug repurposing is becoming interesting in terms of offering advantages over the traditional drug development, once drug discovery is a costly, time-consuming, and highly risky process. In particular, with the coronavirus disease (COVID-19) declared by World Health Organization as a global pandemic, there has emerged a considerable need to develop therapeutic agents capable of preventing viral outbreaks. Concomitantly, well-known and long-used drugs such as acyclovir (Acv) have been tested against COVID-19. Acv is a guanosine analogue that acts as an antiviral drug, commonly used to treat herpes simplex virus (HSV), genital herpes, and varicella zoster virus (VZV). Acv showed to inhibit viral proteases, multiple viral genes expression, and RNA-Dependent RNA Polymerase, helping to recover COVID-19 patients. However, ACV is a BCS class III/IV drug, with low permeability and/or slight water solubility (concentration-dependent). Given the repurposing eligibility of Acv, in this work, two new salts of this drug are presented (nitrate and sulfate), with the aim of improving its pharmacokinetic properties. The new salts were evaluated by X-ray diffraction, and thermal and spectroscopic analyses. A third salt, a chloride one, was also characterized and used for comparison.
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CHEN, T., D. THORNTON, and M. HO. "Reduction of dimethyl sulfoxide by dihydrohalide salts of pharmaceuticals." International Journal of Pharmaceutics 59, no. 3 (March 30, 1990): 211–16. http://dx.doi.org/10.1016/0378-5173(90)90111-g.

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47

Mithu, Md Sadeque Hossain, Steven A. Ross, Bruce D. Alexander, and Dennis Douroumis. "Solid state thermomechanical engineering of high-quality pharmaceutical salts via solvent free continuous processing." Green Chemistry 22, no. 2 (2020): 540–49. http://dx.doi.org/10.1039/c9gc03528a.

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48

Acebedo-Martínez, Francisco Javier, Alicia Domínguez-Martín, Carolina Alarcón-Payer, Alejandro Sevillano-Páez, Cristóbal Verdugo-Escamilla, Josefa María González-Pérez, Fernando Martínez-Checa, and Duane Choquesillo-Lazarte. "Enhanced NSAIDs Solubility in Drug–Drug Formulations with Ciprofloxacin." International Journal of Molecular Sciences 24, no. 4 (February 7, 2023): 3305. http://dx.doi.org/10.3390/ijms24043305.

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Drug–drug salts are a kind of pharmaceutical multicomponent solid in which the two co-existing components are active pharmaceutical ingredients (APIs) in their ionized forms. This novel approach has attracted great interest in the pharmaceutical industry since it not only allows concomitant formulations but also has proved potential to improve the pharmacokinetics of the involved APIs. This is especially interesting for those APIs that have relevant dose-dependent secondary effects, such as non-steroidal anti-inflammatory drugs (NSAIDs). In this work, six multidrug salts involving six different NSAIDs and the antibiotic ciprofloxacin are reported. The novel solids were synthesized using mechanochemical methods and comprehensively characterized in the solid state. Moreover, solubility and stability studies, as well as bacterial inhibition assays, were performed. Our results suggest that our drug–drug formulations enhanced the solubility of NSAIDs without affecting the antibiotic efficacy.
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Liu, Lixin, Dongyu Zou, Yunan Zhang, Dajun Zhang, Yu Zhang, Qiang Zhang, Jian Wang, Shaoyu Zeng, and Conggang Wang. "Assembly of three pharmaceutical salts/cocrystals of tetrahydroberberine with sulfophenyl acids: improving the properties by formation of charge-assisted hydrogen bonds." New Journal of Chemistry 43, no. 12 (2019): 4886–94. http://dx.doi.org/10.1039/c9nj00131j.

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Mishra, SK, A. Kumar, RK Chaturvedi, and SN Pandeya. "Vanadium salts versus diabetes: An overview." Systematic Reviews in Pharmacy 1, no. 2 (2010): 172. http://dx.doi.org/10.4103/0975-8453.75073.

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