The Co‐Crystal Approach to Improve the Exposure of a Water‐Insoluble Compound: AMG 517 Sorbic Acid Co‐Crystal Characterization and Pharmacokinetics

Bak, Annette; Gore, Anu; Yanez, Evelyn; Stanton, Mary K.; Tufekcic, Sunita; Syed, Rashid; Akrami, Anna; Rose, Mark J.; Surapaneni, Sekhar; Bostick, Tracy; King, Anthony O.; Neervannan, Sesha; Ostovic, Drazen; Koparkar, Arun

doi:10.1002/jps.21280

Cited by 205 publications

(207 citation statements)

References 32 publications

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“…The amorphous 2:1 salt was superior to the systems investigated in terms of the solubility behaviour presenting long-lasting drug supersaturation concentrations, characteristic of so-called "spring", but not "spring-parachute" systems. 56 Further studies are required to reveal the biopharmaceutical potential of such supersaturating systems, especially in the context of formulation development.…”

Section: Discussionmentioning

confidence: 99%

Formation and Physicochemical Properties of Crystalline and Amorphous Salts with Different Stoichiometries Formed between Ciprofloxacin and Succinic Acid

Paluch¹,

McCabe²,

Müller‐Bunz

et al. 2013

Mol. Pharmaceutics

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Multi-ionisable compounds, such as dicarboxylic acids, offer the possibility of forming salts of drugs with multiple stoichiometries. Attempts to crystallise ciprofloxacin, a poorly water soluble, amphoteric molecule with succinic acid (S) resulted in isolation of ciprofloxacin hemisuccinate (1:1) trihydrate (CHS-I) and ciprofloxacin succinate (2:1) tetrahydrate (CS-I). Anhydrous ciprofloxacin hemisuccinate (CHS-II) and anhydrous ciprofloxacin succinate (CS-II) were also obtained. It was also possible to obtain stoichiometrically equivalent amorphous salt forms, CHS-III and CS-III, by spray drying and milling, respectively, of the drug and acid. Anhydrous CHS and CS had melting points at ~215 and ~228 °C, while the glass transition temperatures of CHS-III and CS-III were ~101 and ~79 °C, respectively. Dynamic solubility studies revealed the metastable nature of CS-I in aqueous media, resulting in a transformation of CS-I to a mix of CHS-I and ciprofloxacin 1:3.7 hydrate, consistent with the phase diagram. CS-III was observed to dissolve non-congruently leading to high and sustainable drug solution concentrations in water at 25 and 37 ºC, with the ciprofloxacin concentration of 58.8±1.18 mg/ml after 1 hour of the experiment at 37 ºC. This work shows that crystalline salts with multiple stoichiometries and amorphous salts have diverse pharmaceutically-relevant properties, including molecular, solid state and solubility characteristics.

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Section: Discussionmentioning

confidence: 99%

Formation and Physicochemical Properties of Crystalline and Amorphous Salts with Different Stoichiometries Formed between Ciprofloxacin and Succinic Acid

Paluch¹,

McCabe²,

Müller‐Bunz

et al. 2013

Mol. Pharmaceutics

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show abstract

“…66,67) The solubility and dissolution profiles of solid pharmaceuticals depend on the interactions between components in solids (e.g., crystal lattice energy) as well as in the solvent, which are determined by the hydrophobicity of the active ingredient.…”

Section: Solubility and Dissolution Profile Of Cocrys-mentioning

confidence: 99%

“…They have shown that higher API concentrations in main absorption regions, such as the small intestine, increase the bioavailability of low-solubility APIs in certain cocrystals (e.g., itraconazole-dicarboxylic acids). 66,67,75) These data require a careful evaluation of their relevance to humans because factors influencing in vivo absorption, such as structure and fluid content of the gastrointestinal tract, dramatically vary among species. The large difference in hydrophobic API dissolution between fed and fasted conditions with respect to bile acid concentration serves as an apparent factor affecting bioavailability.…”

Section: Solubility and Dissolution Profile Of Cocrys-mentioning

confidence: 99%

Characterization and Quality Control of Pharmaceutical Cocrystals

Izutsu¹,

Koide²,

Takata

et al. 2016

Chem. Pharm. Bull.

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Recent active research and new regulatory guidance on pharmaceutical cocrystals have increased the rate of their development as promising approaches to improve handling, storage stability, and bioavailability of poorly soluble active pharmaceutical ingredients (APIs). However, their complex structure and the limited amount of available information related to their performance may require development strategies that differ from those of single-component crystals to ensure their clinical safety and efficacy. This article highlights current methods of characterizing pharmaceutical cocrystals and approaches to controlling their quality. Different cocrystal regulatory approaches between regions are also discussed. The physical characterization of cocrystals should include elucidating the structure of their objective crystal form as well as their possible variations (e.g., polymorphs, hydrates). Some solids may also contain crystals of individual components. Multiple processes to prepare pharmaceutical cocrystals (e.g., crystallization from solutions, grinding) vary in their applicable ingredients, scalability, and characteristics of resulting solids. The choice of the manufacturing method affects the quality control of particular cocrystals and their formulations. In vitro evaluation of the properties that govern clinical performance is attracting increasing attention in the development of pharmaceutical cocrystals. Understanding and mitigating possible factors perturbing the dissolution and/ or dissolved states, including solution-mediated phase transformation (SMPT) and precipitation from supersaturated solutions, are important to ensure the bioavailability of orally administrated lower-solubility APIs. The effect of polymer excipients on the performance of APIs emphasizes the relevance of formulation design for appropriate use.

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“…Pharmaceutical co-crystals, combining an API and an acceptable co-former, 11 have the potential for enhancing the physical properties of the API, positively impacting its solubility, stability, oral bioavailability and processability, without compromising its biological function 1,9,[12][13][14][15][16][17][18][19][20][21] .…”

Section: Introductionmentioning

confidence: 99%

Co-crystals of diflunisal and isomeric pyridinecarboxamides – a thermodynamics and crystal engineering contribution

et al. 2016

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This version is available at https://strathprints.strath.ac.uk/56947/ Strathprints is designed to allow users to access the research output of the University of Strathclyde. Unless otherwise explicitly stated on the manuscript, Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Please check the manuscript for details of any other licences that may have been applied. You may not engage in further distribution of the material for any profitmaking activities or any commercial gain. You may freely distribute both the url (https://strathprints.strath.ac.uk/) and the content of this paper for research or private study, educational, or not-for-profit purposes without prior permission or charge.Any correspondence concerning this service should be sent to the Strathprints administrator: strathprints@strath.ac.ukThe Strathprints institutional repository (https://strathprints.strath.ac.uk) is a digital archive of University of Strathclyde research outputs. It has been developed to disseminate open access research outputs, expose data about those outputs, and enable the management and persistent access to Strathclyde's intellectual output.1 To whom correspondence should be addressed. E-mail: antonio.evora@uc.pt Tel.: Co-crystals of diflunisal and isomeric pyridinecarboxamides a thermodynamics and crystal engineering contribution +351239854450 ABSTRACTDiflunisal is an anti-inflammatory non-steroidal drug, class II of the Biopharmaceutical Classification System, that has recently been the subject of renewed interest due to its potential use in the oral therapy of familial amyloid polyneuropathy. In this work, a thermodynamic based approach is used to investigate binary mixtures (diflunisal + picolinamide) and (diflunisal + isonicotinamide) in order to identify solid forms potentially useful to improve the biopharmaceutical performance of this active pharmaceutical ingredient.Special emphasis is put on the research of co-crystals and on the influence of structural changes in the pyridinecarboxamide co-former molecules on co-crystal formation with diflunisal. The thermodynamic based methodology described by ter Horst et al. in 2010 indicates that the formation of co-crystals is thermodynamically feasible for both systems. The binary solid-liquid phase diagrams are built and allow identifying unequivocally the formation of co-crystals of diflunisal with each of the two isomers and also their stoichiometry: 1:1, (diflunisal:co-former) in the case of pyridine-2-carboxamide, picolinamide, and 2

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The Co‐Crystal Approach to Improve the Exposure of a Water‐Insoluble Compound: AMG 517 Sorbic Acid Co‐Crystal Characterization and Pharmacokinetics

Cited by 205 publications

References 32 publications

Formation and Physicochemical Properties of Crystalline and Amorphous Salts with Different Stoichiometries Formed between Ciprofloxacin and Succinic Acid

Formation and Physicochemical Properties of Crystalline and Amorphous Salts with Different Stoichiometries Formed between Ciprofloxacin and Succinic Acid

Characterization and Quality Control of Pharmaceutical Cocrystals

Co-crystals of diflunisal and isomeric pyridinecarboxamides – a thermodynamics and crystal engineering contribution

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